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Mucosal Inflammation (mucosal + inflammation)
Kinds of Mucosal Inflammation Selected AbstractsLong-lasting changes in small intestinal transport following the recovery from Trichinella spiralis infectionNEUROGASTROENTEROLOGY & MOTILITY, Issue 3 2006K. Venkova Abstract, Changes in intestinal motility and visceral sensitivity are found after resolution of acute enteric inflammation. The study investigates whether a transient nematode-induced intestinal inflammation may result in long-lasting remodelling of epithelial transport. Ferrets infected with Trichinella spiralis or sham-infected animals were euthanized on day 10, 30 or 60 postinfection (PI) and the jejunum was isolated. The net transport of electrolytes was measured electrophysiologically as transmucosal short-circuit current (Isc) and responses to electrical field stimulation (EFS: 1,32 Hz) or secretagogues were investigated. Myeloperoxidase (MPO) activity, a marker of mucosal inflammation, was maximal during the enteric stage of T. spiralis infection (day 10 PI) and returned to normal on days 30 and 60 PI. Mucosal inflammation caused a reduction in basal Isc, increased electrical conductance (G) and decreased the maximal responses to EFS, carbachol or histamine. On days 30 and 60 PI the inflammation resolved and basal electrogenic transport appeared normal; however, the secretion induced by EFS, carbachol or histamine remained suppressed. Moreover, EFS-induced responses were shifted from predominantly cholinergic in controls to non-cholinergic in the infected animals. The results suggest that a transient small intestinal inflammation causes a long-term remodelling of epithelial function. [source] DIAGNOSIS AND CLINICAL COURSE OF ULCERATIVE GASTRODUODENAL LESION ASSOCIATED WITH ULCERATIVE COLITIS: POSSIBLE RELATIONSHIP WITH POUCHITISDIGESTIVE ENDOSCOPY, Issue 4 2010Takashi Hisabe Background and Aim:, Ulcerative colitis (UC) is not only characterized by pathological lesions localized to colonic mucosa, but also to various complications involving other organs, including postoperative pouchitis. Among these complications, diffuse gastroduodenitis with lesions resembling colonic lesions has been reported, albeit rarely. The aim of the present study was to attempt to characterize the lesions of the upper gastrointestinal tract occurring as a complication of UC, and to assess the frequency and clinical course of these lesions. Methods:, A total of 322 UC patients who had undergone upper gastrointestinal endoscopy were retrospectively analyzed. We assessed the frequency of endoscopic findings, including diffuse gastroduodenal lesions resembling colonic lesions. Ulcerative gastroduodenal lesion (UGDL) associated with UC was diagnosed if lesions satisfied the following criteria: (i) improvement of the lesions with treatment of UC; and/or (ii) resemblance to UC in pathological findings. Results:, UGDL satisfying the aforementioned criteria was found in 15 (4.7%) of 322 patients. All the 15 patients had UGDL accompanied by pancolitis or after proctocolectomy. Frequency in 146 patients with pancolitis was 6.2% (nine patients) and that in 81 patients who had undergone proctocolectomy was 7.4% (six patients). Four patients with diffuse ulcerative upper-gastrointestinal mucosal inflammation (DUMI) had pouchitis. In all patients except one, the lesions resolved easily with medical treatment. Conclusions:, In more than half of the post-proctocolectomy patients, UGDL was related to the occurrence of pouchitis. The existence of characteristic UGDL must be taken into account in the diagnosis and treatment of UC, and UGDL is possibly related to the occurrence of pouchitis. [source] Oral health and oral implant status in edentulous patients with implant-supported dental prostheses who are receiving long-term nursing careGERODONTOLOGY, Issue 4 2009Rita Isaksson Aim:, The aim of this study was to investigate oral health and oral implant status in a group of edentulous patients receiving long-term residential or nursing care (LTC), all of whom had implant-supported fixed or removable dental prostheses. Material and methods:, A dental examination was performed on a total of 3310 patients receiving LTC and from this population 35 edentulous patients in whom dental implants had been placed formed the cohort for this study. All examinations were performed by a specialist in hospital dentistry and took place in the patients' own home environment. Oral health was assessed by means of a protocol which evaluated oral hygiene status, possible oral mucosal inflammation and oral mucosal friction levels. Any problems with the implant-supported prosthesis, implant mobility or other complications were also assessed. In addition, patients were asked about any oral symptoms and their usual oral hygiene procedures. Results:, About half of the subjects (17/35) were registered as having no/mild inflammation with 18 of 35 having moderate/severe inflammation. Twelve of the 35 patients had good/acceptable oral hygiene and 23 of 35 had poor/bad oral hygiene. Twenty-one of the 35 patients depended on help from the nursing personnel for their daily oral hygiene procedures. Obvious problems with food impaction were noted in 11 patients. A total of 229 implants had been placed in 43 jaws supporting 40 full arch-fixed prostheses and three implant-borne overdentures. There was no evidence of mobility or fractures of either the implants or the prostheses. Fifteen implants showed some exposed screw threads. Pus was exuding from one implant site and general peri-implant gingival hyperplasia was noted in two patients. Twenty-four patients were completely satisfied with the function and appearance of their implant-supported prostheses. Two patients were totally dissatisfied. Conclusion:, This study indicates that oral implant therapy can be considered as a treatment of choice in elderly patients, even if oral hygiene is sub-optimal. [source] Cross-Primed CD8+ Cytotoxic T cells Induce Severe Helicobacter -associated Gastritis in the Absence of CD4+ T cellsHELICOBACTER, Issue 5 2007Toshiro Fukui Abstract Background:, Although previous studies have reported important roles of CD4+ type1-helper T cells and regulatory T cells in Helicobacter -associated gastritis, the significance of CD8+ cytotoxic T cells remains unknown. To study the roles of CD8+ T cells, we examined the immune response in the gastric mucosa of Helicobacter felis -infected major histocompatibility complex (MHC) class II-deficient (II,/,) mice, which lack CD4+ T cells. Materials and methods:, Stomachs from H. felis -infected wild-type and infected MHC II,/, mice were examined histologically and immunohistochemically. Gastric acidity and serum levels of anti- H. felis antibodies were measured. The expression of pro-inflammatory and anti-inflammatory cytokine, Fas-ligand, perforin, and Foxp3 genes in the gastric mucosa was investigated. Results:,H. felis -infected MHC II,/, mice developed severe gastritis, accompanied by marked infiltration of CD8+ cells. At 1 and 2 months after inoculation, mucosal inflammation and atrophy were more severe in MHC II,/, mice, although gastritis had reached similar advanced stages at 3 months after inoculation. There was little infiltration of CD4+ cells, and no Foxp3 -positive cells were detected in the gastric mucosa of the infected MHC II,/, mice. The expression of the interleukin-1, and Fas-ligand genes was up regulated, but that of Foxp3 was down regulated in the infected MHC II,/, mice. Serum levels of anti- H. felis antibodies were lower in the infected MHC II,/, mice, despite severe gastritis. Conclusions:, The present study suggests that cross-primed CD8+ cytotoxic T cells can induce severe H. -associated gastritis in the absence of CD4+ helper T cells and that Foxp3 -positive cells may have an important role in the control of gastric inflammation. [source] Helicobacter pylori Infection in the Cat: Evaluation of Gastric Colonization, Inflammation and FunctionHELICOBACTER, Issue 1 2001Kenneth W. Simpson Background. Further elucidation of the consequences of Helicobacter pylori infection on gastric mucosal inflammation and gastric secretory function would be facilitated by an animal model that is susceptible to infection with H. pylori, is broadly similar in gastric physiology and pathology to people, and is amenable to repeated non-invasive evaluation. The goal of this study was to examine the interrelationship of bacterial colonization, mucosal inflammation and gastric secretory function in cats with naturally acquired H. pylori infection. Materials and Methods. Twenty clinically healthy cats with naturally acquired H. pylori infection (cagA,, picB) and 19 Helicobacter -free cats were evaluated. Gastric colonization was determined by tissue urease activity, light microscopy, culture and PCR. The mucosal inflammatory response was evaluated by light microscopy, and by RT-PCR of the pro-inflammatory cytokines IL-1,, IL-1,, IL-8 and TNF-, in gastric mucosa. Gastric secretory function was assessed by measuring pentagastrin-stimulated acid secretion, fasting plasma gastrin, and antral mucosal gastrin and somatostatin immunoreactivity. Results. H. pylori colonized the pylorus, fundus and cardia in similar density. Bacteria were observed free in the lumen of gastric glands and were also tightly adherent to epithelial cells where they were associated with microvillus effacement. Mononuclear inflammation, lymphoid follicle hyperplasia, atrophy and fibrosis were observed primarily in H. pylori -infected cats, with the pylorus most severely affected. Neutrophilic and eosinophilic infiltrates, epithelial dysplasia, and up-regulation of mucosal IL-1, and IL-8 were observed solely in infected cats. Fasting plasma gastrin concentrations and pentagastrin-stimulated acid output were similar in both infected and uninfected cats. There was no relationship of bacterial colonization density or gastric inflammation to plasma gastrin concentrations or gastric acid output. Conclusions. The pattern of colonization and the mucosal inflammatory response in cats with naturally acquired H. pylori are broadly similar to those in infected people, particularly children, and non-human primates. The upregulation of IL-8 in infected cats was independent of cagA and picB. Our findings argue against a direct acid-suppressing effect of H. pylori on the gastric secretory-axis in chronically infected cats. Abbreviations: RT-PCR, reverse transcriptase polymerase chain reaction, HLO; Helicobacter -like organisms. [source] Does psychological counseling alter the natural history of inflammatory bowel disease?INFLAMMATORY BOWEL DISEASES, Issue 4 2010Mahmood Wahed MBBS Abstract Background: There is increasing evidence that psychological stress can increase mucosal inflammation and worsen the course of inflammatory bowel disease (IBD). We have now assessed whether psychotherapy by a counselor specially trained in the management of IBD can influence the course of disease. Methods: Using retrospective case note review, we compared the course of IBD in 24 patients (13 ulcerative colitis; 11 Crohn's disease), during the year before (year 1) and the year after referral (year 2) for supportive outpatient psychotherapy to an IBD counselor, to that of 24 IBD controls who were matched to individual cases for age, sex, disease, duration of disease, medication at baseline, and for relapse rate in year 1. Counselor assessments were made using a visual analog scale 0,6 (0 denotes poor, 6 excellent response to counseling). The results are shown as median (range). Results: Patients were referred for counseling because of disease-related stress (14 patients), work problems (3), concerns about surgery (5), and bereavement (2); they received 6 (1,13) 1-hour sessions in year 2. In the year after starting counseling (year 2), patients had fewer relapses (0 [0,2]) and outpatient attendances (3.5 [1,10]) than in the year before referral (year 1) (2 [0,5], P = 0.0008; and 6.5 [1,17], P = 0.0006, respectively; furthermore, steroid usage (1 course [0,4] before, 0 [0,2] after, P = 0.005) and relapse-related use of other IBD medications declined during psychotherapy (1 drug [0,5] before, 0 [0,2] after, P = 0.002). There were no differences in any of these measures between years 1 and 2 in the control group. Numbers of hospital admissions did not change between year 1 and 2 in either group. In the 20 patients who attended >1 session counseling helped solve stress-related difficulties (counselor's score 4 [3,5]), the counselor scored them 4 (3,6) overall in psychological well-being after the counseling sessions. Conclusions: IBD-focused counseling may improve not only psychological well-being, but also the course of IBD in individuals with psychosocial stress. (Inflamm Bowel Dis 2009;) [source] Blockage of the neurokinin 1 receptor and capsaicin-induced ablation of the enteric afferent nerves protect SCID mice against T-cell-induced chronic colitisINFLAMMATORY BOWEL DISEASES, Issue 8 2009Monika Gad PhD Abstract Background: The neurotransmitter substance P (SP) released by, and the transient receptor potential vanilloid (TRPV1), expressed by afferent nerves, have been implicated in mucosal neuro-immune-regulation. To test if enteric afferent nerves are of importance for the development of chronic colitis, we examined antagonists for the high-affinity neurokinin 1 (NK-1) SP receptor and the TRPV1 receptor agonist capsaicin in a T-cell transfer model for chronic colitis. Methods: Chronic colitis was induced in SCID mice by injection of CD4+CD25, T cells. The importance of NK-1 signaling and TRPV1 expressing afferent nerves for disease development was studied in recipient SCID mice systemically treated with either high-affinity NK-1 receptor antagonists or neurotoxic doses of capsaicin. In addition, we studied the colitis-inducing effect of NK-1 receptor deleted CD4+CD25, T cells. Results: Treatment with the NK-1 receptor antagonist CAM 4092 reduced the severity of colitis, but colitis was induced by NK-1 receptor-deleted T cells, suggesting that SP in colitis targets the recipient mouse cells and not the colitogenic donor T cells. Capsaicin-induced depletion of nociceptive afferent nerves prior to CD4+CD25, T-cell transfer completely inhibited the development of colitis. Conclusions: Our data demonstrate the importance of an intact enteric afferent nerve system and NK-1 signaling in mucosal inflammation and may suggest new treatment modalities for patients suffering from inflammatory bowel disease. (Inflamm Bowel Dis 2009) [source] High-frequency haplotypes in the X chromosome locus TLR8 are associated with both CD and UC in femalesINFLAMMATORY BOWEL DISEASES, Issue 3 2009Masayuki Saruta MD Abstract Background: TNF-, and IL-1 have been associated with mucosal inflammation in both Crohn's disease (CD) and ulcerative colitis (UC). Innate immune defects have been associated with CD, specifically CARD15/NOD2. Recently, Toll-like receptor 8 (TLR8) signaling has been shown to enhance generation of both cytokines. Interestingly, TLR8 is located on the X chromosome and inflammatory bowel disease (IBD) has been associated with abnormalities of the X chromosome. The aim was to test whether TLR8 haplotypes are associated with IBD. Methods: Subjects (735 CD, 343 UC, 245 controls) were genotyped. Single nucleotide polymorphisms (SNPs) were chosen to tag common Caucasian haplotypes. Results: Both "risk (H4)" and "protective (H1)" TLR8 haplotypes were observed associated with CD in females. Eighteen percent of CD females had H4 compared with 9% of controls (P = 0.02). Fifty-nine percent of CD females had H1 compared with 72% of controls (P = 0.01). H1 was also negatively associated with UC in females (59% of UC, 72% of controls P = 0.03). Diplotype analysis of CD, UC, and all IBD in females revealed that 2 protective haplotypes (H1/H1) had a markedly diminished odds ratio, 0.4,0.5. The presence of a risk haplotype (H4 / not H1) had a significantly increased odds ratio, 2.0,2.2. Thus, the risk for IBD was 4,5 times higher in females with 1 risk haplotype than with the protective/protective diplotype. Conclusions: TLR8 is an X-linked IBD susceptibility gene with both common predisposing and protecting haplotypes. These associations further emphasize the importance of genetic variation in innate immunity as determinants, not only of CD, but of UC as well. (Inflamm Bowel Dis 2008) [source] IL23R haplotypes provide a large population attributable risk for Crohn's diseaseINFLAMMATORY BOWEL DISEASES, Issue 9 2008Kent D. Taylor PhD Abstract Background: The IL-23 pathway plays a pivotal role in the development of chronic mucosal inflammation seen in the inflammatory bowel diseases. Multiple studies have now established the contribution of the interleukin 23 receptor gene (IL23R) to Crohn's disease (CD) risk in general and of the IL23R R381Q variant in particular. The aim of this work was to estimate the total contribution of this gene to CD risk test using a haplotype approach. Methods: In all, 763 CD subjects and 254 controls were genotyped for single nucleotide polymorphisms in the IL23R gene using Illumina and ABI methods. Haplotypes were assigned using PHASEv2 and tested for association with CD by chi-square and permutation. Results: Haplotypes with both increased and decreased risk for CD were observed in 2 of the 4 observed blocks (Block 2 H1: 55.4% control, 64% CD, P = 0.019; H2: 64.5% control, 54.4% CD, P = 0.006; Block 3 H1: 55.8% control, 64.4% CD, P = 0.013; H2: 47.0% control, 36.6% CD, P = 0.001). The population attributable risk for these haplotypes was substantially larger than that estimated for the IL23R R381Q variant (Block 2 H1 and block 3 H1 ,20%, compared with ,4% for Block 3 H6, containing the variant). Conclusions: These observations suggest that IL23R makes a substantial contribution to CD susceptibility, larger than that estimated from the population frequency of the R381Q variant. These observations also support the expectation that finding "hits" from genomewide association studies will be but an important chapter in the story of unraveling the genetic contribution to CD, rather than the final chapter that brings clarity to all the plot twists of a complicated story. (Inflamm Bowel Dis 2008) [source] Activation of an IL-6:STAT3-dependent transcriptome in pediatric-onset inflammatory bowel diseaseINFLAMMATORY BOWEL DISEASES, Issue 4 2008Rebecca Carey MD Abstract Background: While activation of the IL-6-dependent transcription factor signal transducer and activator of transcription 3 (STAT3) has been implicated in the pathogenesis of inflammatory bowel disease (IBD), a direct effect on mucosal gene expression and inflammation has not been shown. We hypothesized that a proinflammatory IL-6:STAT3-dependent biological network would be up regulated in pediatric-onset IBD patients, and would be associated with the severity of mucosal inflammation. Methods: Patients with pediatric-onset IBD were enrolled at diagnosis and during therapy. Serum cytokine analysis was performed using Bioplex. STAT3 phosphorylation (pSTAT3) in peripheral blood leukocytes (PBLs) was assessed by flow cytometry. Immunohistochemistry of colonic mucosa was used to localize pSTAT3 and STAT3 target genes. Microarray analysis was used to determine RNA expression profiles from colon biopsies. Results: Circulating IL-6 was upregulated in active IBD patients at diagnosis and during therapy. STAT3 activation was increased in PB granulocytes, IL-6-stimulated CD3+/CD4+ lymphocytes, and affected colon biopsies of IBD patients. The frequency of pSTAT3+ PB granulocytes and colon epithelial and lamina propria cells was highly correlated with the degree of mucosal inflammation. Microarray and Ingenuity Systems bioinformatics analysis identified IL-6:STAT3-dependent biological networks upregulated in IBD patients which control leukocyte recruitment, HLA expression, angiogenesis, and tissue remodeling. Conclusions: A proinflammatory IL6:STAT3 biologic network is upregulated in active pediatric IBD patients at diagnosis and during therapy. Specific targeting of this network may be effective in reducing mucosal inflammation. (Inflamm Bowel Dis 2007) [source] Characterization of cecal gene expression in a differentially susceptible mouse model of bacterial-induced inflammatory bowel diseaseINFLAMMATORY BOWEL DISEASES, Issue 7 2007Matthew H. Myles DVM Abstract Background: A/JCr mice develop typhlitis in response to Helicobacter hepaticus infection, whereas C57BL/6 mice coexist with this bacterium in a "commensal" relationship and do not develop disease even during prolonged colonization. Methods: To determine mechanisms that control this balance between responsiveness and nonresponsiveness, the mucosal response of A/JCr and C57BL/6 mice to acute H. hepaticus colonization was evaluated using genome-wide profiling. Transcription levels for a subset of gene discoveries were then evaluated longitudinally by semiquantitative real-time reverse-transcriptase polymerase chain reaction (RT-PCR) to identify changes in gene expression that occur during progression from the acute to chronic phase of colonization. To determine whether chronic mucosal inflammation in A/JCr mice was mediated through a Th1 mechanism, as was inferred from the gene expression data, mice with typhlitis were treated with neutralizing antibody targeting IL-12/23p40 or IFN-gamma and the response to treatment was determined by cecal lesion severity and transcription of disease-related genes. Results: A/JCr mice had a biphasic expression of proinflammatory genes that corresponded with the acute and chronic phases of disease. In contrast, C57BL/6 mice exhibited a less robust acute transcriptional response that waned by day 30 postinoculation. Sustained upregulation of proinflammatory signals and responsiveness to anti-IL-12/23p40 and anti-IFN-, antibody suggests that inflammation in A/JCr mice was mediated through a Th1 mechanism. Prolonged upregulation of SOCS3 during the acute response to colonization suggests that C57BL/6 mice maintain mucosal homeostasis, at least in part by attenuating responsiveness to cytokine signaling. Conclusions: Collectively, these findings provide a foundation for understanding the immunological mechanisms that confer resistance or susceptibility to H. hepaticus -induced typhlitis. (Inflamm Bowel Dis 2007) [source] Expression and functional characterization of FOXP3+CD4+ regulatory T cells in ulcerative colitis,INFLAMMATORY BOWEL DISEASES, Issue 2 2007Qi T. Yu BS Abstract Background: CD4+CD25+ regulatory T cells (TR) can prevent or treat experimental murine colitis but little is known about their potential role in human inflammatory bowel disease (IBD). FOXP3 is a transcription factor that plays a critical role in the development and function of CD4+CD25+ TR. The aim of this study was to examine the presence and functional characteristics of TR cells in colonic lymphoid tissues in patients with ulcerative colitis (UC). Methods: FOXP3 expression was assessed by flow cytometry, immunohistochemistry, and reverse-transcriptase polymerase chain reaction (RT-PCR). Functional characterization of CD4+CD25+ cells was analyzed by suppression of proliferation and secretion of cytokines by cocultured effector CD4+CD25, T cells. Results: FOXP3+CD4+ T cells are increased in the lamina propria (LP) of inflamed and noninflamed areas of UC colon compared to normal colon. CD4+CD25+ T cells in UC mesenteric lymph nodes (MLN) express FOXP3 mRNA and protein and suppress the proliferation of autologous MLN CD4+CD25, T cells. The suppressor activity of MLN CD4+CD25+ T cells is cell contact-dependent but cytokine-independent. In addition, CD4+CD25+ T cells potently suppress the production of both Th1 (IFN-,, IL-2) and Th2 (IL-5, IL-13) cytokines by cocultured CD4+CD25, T cells. FOXP3+ cells localized in the T-cell-rich areas of MLN and occasionally present in the follicles. Conclusions: There is an expansion of FOXP3+CD4+ T cells in mucosal lymphoid tissues in UC. CD4+CD25+ isolated from UC MLN express FOXP3 and display features of TR cells in spite of active mucosal inflammation. These data suggest that their suppressor activity may be abrogated in vivo or they are unable to counterbalance the chronic mucosal inflammation in UC. (Inflamm Bowel Dis 2007) [source] Bacterial antigens alone can influence intestinal barrier integrity, but live bacteria are required for initiation of intestinal inflammation and injuryINFLAMMATORY BOWEL DISEASES, Issue 6 2006Beate C. Sydora PhD Abstract Intestinal flora plays a critical role in the initiation and perpetuation of inflammatory bowel disease. This study examined whether live fecal bacteria were necessary for the initiation of this inflammatory response or whether sterile fecal material would provoke a similar response. Three preparations of fecal material were prepared: (1) a slurry of live fecal bacteria, (2) a sterile lysate of bacterial antigens, and (3) a sterile filtrate of fecal water. Each preparation was introduced via gastric gavage into the intestines of axenic interleukin-10 gene-deficient mice genetically predisposed to develop inflammatory bowel disease. Intestinal barrier integrity and degrees of mucosal and systemic inflammations were determined for each preparation group. Intestinal barrier integrity, as determined by mannitol transmural flux, was altered by both live fecal bacterial and sterile lysates of bacterial antigens, although it was not altered by sterile filtrates of fecal water. However, only live fecal bacteria initiated mucosal inflammation and injury and a systemic immune response. Fecal bacterial antigens in the presence of live bacteria and sterile fecal bacterial antigens have different effects on the initiation and perpetuation of intestinal inflammation. [source] Impact of elemental diet on mucosal inflammation in patients with active Crohn's disease: Cytokine production and endoscopic and histological findingsINFLAMMATORY BOWEL DISEASES, Issue 6 2005Takayuki Yamamoto MD Abstract Background: The aim of this study was to examine the impact of elemental diet on mucosal inflammation in Crohn's disease (CD), mainly by cytokine measurements. Methods: Twenty-eight consecutive patients with active CD were treated with an elemental diet (Elental) for 4 weeks. The mucosal biopsies were obtained from the terminal ileum and large bowel before and after treatment. As a control group, mucosal biopsies were obtained from 20 patients without inflammation. Mucosal cytokine concentrations were measured by enzyme-linked immunosorbent assay. Results: After treatment, clinical remission was achieved in 20 patients (71%). Endoscopic healing and improvement rates were 44% and 76% in the terminal ileum and 39% and 78% in the large bowel, respectively. Histologic healing and improvement rates were 19% and 54% in the terminal ileum and 20% and 55% in the large bowel, respectively. Before treatment, the mucosal concentrations of interleukin (IL)-1,, IL-1 receptor antagonist (IL-1ra), IL-6, IL-8, and tumor necrosis factor-, in the ileum and large bowel were significantly higher than in controls. These cytokine concentrations decreased to the levels of control after treatment. IL-1ra/IL-1, ratio in the ileum and large bowel was significantly lower than in controls before treatment. The ratio increased to the level of controls after treatment. The endoscopic and histologic healing of the mucosal inflammation was associated with a decline of the mucosal cytokines and an increase of the IL-1ra/IL-1, ratio. Conclusions: The elemental diet (Elental) reduced mucosal cytokine production and corrected an imbalance between proinflammatory and anti-inflammatory cytokines in CD. [source] Catalposide, a compound isolated from Catalpa Ovata, attenuates induction of intestinal epithelial proinflammatory gene expression and reduces the severity of trinitrobenzene sulfonic acid-induced colitis in miceINFLAMMATORY BOWEL DISEASES, Issue 5 2004Sang-Wook Kim MD Abstract Certain irinoid-producing plants have been used as herbal anti-inflammatory remedies. Here we evaluated whether catalposide (CATP), a single compound isolated from irinoid-producing plant Catalpa ovata, has a potential for preventing or ameliorating diseases characterized by mucosal inflammation. Preliminary microarray-based gene expression test revealed that CATP, which alone did not significantly affect expression of any of the >8,000 genes analyzed, attenuated the expression of tumor necrosis factor-, (TNF-,)-induced proinflammatory genes including interleukin-8 (IL-8) in human intestinal epithelial HT-29 cells. Down-regulation of IL-8 mRNA accumulation was also reflected by the decreased IL-8 secretion in CATP-treated HT-29 cells. The signal transduction study revealed that CATP significantly attenuates TNF-,-mediated p38 and extracellular signal-regulated kinase (ERK) phosphorylation. Further, CATP reduced NF-,B-mediated transcriptional activation as well as I,-B, degradation. To establish the in vivo relevance of these findings, we examined whether CATP could affect intestinal inflammation in vivo using the mouse model of trinitrobenzene sulfonic acid (TNBS)-induced inflammatory colitis. Intrarectal administration of CATP dramatically reduced the weight loss, colonic damage, and mucosal ulceration that characterize TNBS colitis. Moreover, CATP suppressed the expression of TNF-,, interleukin-1,, and intercellular adhesion molecule-1 along with the inhibition of NF-, B p65 translocation into nucleus in TNBS colitis. Collectively, current results demonstrate that CATP may be an effective agent for the treatment of diseases characterized by mucosal inflammation. [source] Osteopontin as two-sided mediator of intestinal inflammationJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 6 2009Katja Heilmann Abstract Osteopontin (OPN) is characterized as a major amplifier of Th1-immune responses. However, its role in intestinal inflammation is currently unknown. We found considerably raised OPN levels in blood of wild-type (WT) mice with dextran sodium sulfate (DSS)-induced colitis. To identify the role of this mediator in intestinal inflammation, we analysed experimental colitis in OPN-deficient (OPN,/,) mice. In the acute phase of colitis these mice showed more extensive colonic ulcerations and mucosal destruction than WT mice, which was abrogated by application of soluble OPN. Within the OPN,/, mice, infiltrating macrophages were not activated and showed impaired phagocytosis. Reduced mRNA expression of interleukin (IL)-1 , and matrix metalloproteinases was found in acute colitis of OPN,/, mice. This was associated with decreased blood levels of IL-22, a Th17 cytokine that may mediate epithelial regeneration. However, OPN,/, mice showed increased serum levels of tumour necrosis factor (TNF)-,, which could be due to systemically present lipopolysaccharide translocated to the gut. In contrast to acute colitis, during chronic DSS-colitis, which is driven by a Th1 response of the lamina propria infiltrates, OPN,/, mice were protected from mucosal inflammation and demonstrated lower serum levels of IL-12 than WT mice. Furthermore, neutralization of OPN in WT mice abrogated colitis. Lastly, we demonstrate that in patients with active Crohn's disease OPN serum concentration correlated significantly with disease activity. Taken together, we postulate a dual function of OPN in intestinal inflammation: During acute inflammation OPN seems to activate innate immunity, reduces tissue damage and initiates mucosal repair whereas during chronic inflammation it promotes the Th1 response and strengthens inflammation. [source] Expression of MMP-9, MMP-10 and TNF-, and lack of epithelial MMP-1 and MMP-26 characterize pyoderma gangrenosumJOURNAL OF CUTANEOUS PATHOLOGY, Issue 12 2007Ville Bister Background:, Pyoderma gangrenosum (PG) is a non-infectious, autoimmune, chronic ulcer of the skin, often co-existing with inflammatory bowel disease (IBD). Matrix metalloproteinases (MMPs) have been implicated as mediators of tissue destruction in chronic cutaneous and intestinal wounds. Methods:, Twenty-four skin biopsies with clinically and histologically confirmed PG and acute wounds were immunostained for MMP-1, -7, -8, -9, -10 and -26; tissue inhibitors of matrix metalloproteinase (TIMP)-1 and -3 and tumor necrosis factor-, (TNF-,). Results:, MMP-1 was generally expressed by keratinocytes distal from the wound edge, whereas MMP-10 was detected abundantly in the epithelium. MMP-26 was positive in 42% at the migratory front. Abundant stromal expression was evident for MMP-1, -9 and -10, TIMP-1 and -3 and TNF-,. In acute wounds, stromal MMP-1, -9 and -10 and TNF-, were sparse. Conclusions:, Unlike in normally healing cutaneous wounds, MMP-1 and -26 were detected bordering the wound in only a minority of PGs and their lack may thus retard epithelial repair. Particularly, MMP-9 and -10 and TNF-, would be suitable therapeutic targets as they may contribute to the degradation of provisional matrices needed for migration in healing wounds. The presence of MMP-1, -9, -10 and -26 in both PG and IBD ulcers may suggest a similar pathogenesis for cutaneous and mucosal inflammation. [source] Effect of Helicobacter pylori infection on cyclooxygenase-2 expression in gastric antral mucosaJOURNAL OF DIGESTIVE DISEASES, Issue 2 2002Hong LU OBJECTIVE: Helicobacter pylori infection is a major etiological cause of chronic gastritis. Inducible cyclooxygenase (COX-2) is an important regulator of mucosal inflammation. Recent studies indicate that expression of COX-2 may contribute to gastrointestinal carcinogenesis. The aim of this study was to investigate the effects of H. pylori infection and eradication therapy on COX-2 expression in gastric antral mucosa. METHODS: Antral biopsies were taken from 46 H. pylori- infected patients, who also had chronic gastritis, both before and after anti- H. pylori treatment. The COX-2 protein was stained by using immunohistochemical methods and COX-2 expression was quantified as the percentage of epithelial cells expressing COX-2. Gastritis and H. pylori infection status were graded according to the Sydney system. RESULTS: Cyclooxygenase-2 expression was detected in the cytoplasm of gastric antral epithelial cells both before and after the eradication of H. pylori. Cyclooxygenase-2 expression in mucosa with H. pylori infection was compared with the corresponding mucosa after successful H. pylori eradication (20.1 ± 13.1%vs 13.8 ± 5.9%; P < 0.05). At the same time, COX-2 expression in H. pylori -infected mucosa was compared with the normal controls (18.0 ± 14.1%vs 12.3 ± 4.6%, P < 0.05). Expression of COX-2 was correlated with the degree of chronic inflammation (r= 0.78, P < 0.05). CONCLUSIONS: Our results showed that H. pylori infection leads to gastric mucosal overexpression of COX-2 protein, suggesting that the enzyme is involved in H. pylori -related gastric pathology in humans. [source] Nodular gastritis in adults: Clinical features, endoscopic appearance, histopathological features, and response to therapyJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 6 2008Manisha Dwivedi Abstract Background and Aims:, The present study aims to determine the prevalence of nodular gastritis (NG) and ascertain its clinical presentation and histopathological features in adults. It also assesses its association with Helicobacter pylori and the normalization of endoscopic features, symptoms, and histology after anti H. pylori therapy. Methods:, A total of 7140 patients undergoing upper gastrointestinal endoscopy were studied. Patients showing nodularity of the gastric mucosa at endoscopy and an age- and sex-matched control group with normal gastric mucosa underwent biopsies from the gastric antrum and fundus. The biopsies were assessed for the presence of mucosal inflammation, activity, eosinophils, atrophy, lymphoid follicles, H. pylori, and the presence of intestinal metaplasia. Patients with NG were given triple therapy. Endoscopy and biopsy was repeated after 4 weeks of stopping therapy. The symptoms of the patients and histology were assessed pre- and post-therapy. Results:, Thirty-two patients with an age range of 20,65 years presenting with NG and 40 age- and sex-matched controls were included in the study. Presenting symptoms were epigastric pain (56%), nausea (75%), vomiting (50%) and abdominal bloating (62.5%). All these symptoms regressed significantly after 2 week of triple therapy against H. pylori. A marked improvement in histopathological features was seen post-therapy where the presence of lymphoid aggregates, eosinophils in the mucosa, atrophy, and intestinal metaplasia improved significantly (P < 0.05) after therapy, as compared to the control group of patients. Conclusion:, The symptoms of NG and endoscopic features regress significantly after H. pylori therapy with a proton pump inhibitor and two antibiotics and should routinely be given to treat this form of gastritis. This may prevent progression to further complications. [source] Changes in intestinal motility, visceral sensitivity and minor mucosal inflammation after fasting therapy in a patient with irritable bowel syndromeJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 6 2006Michiko Kano [source] Rabeprazole treatment attenuated Helicobacter pylori -associated gastric mucosal lesion formation in Mongolian gerbilsJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 7 2003HIDEKAZU SUZUKI Abstract Background and Aim: Although rabeprazole (RPZ), a proton pump inhibitor, has been reported to have a bactericidal effect on Helicobacter pylori (H. pylori), no studies have been conducted regarding the effect of RPZ on gastric mucosal lesion formation caused by this bacterium. In the present study, we investigated the effect of RPZ on H. pylori -associated gastric mucosal lesion formation. Methods: Sixty-two male Mongolian gerbils were inoculated with H. pylori (ATCC43504) (Hp group) and 60 gerbils with the culture media alone (control group). Some gerbils in the Hp group and in the control group were injected with RPZ (1 mg/kg/day, for 7 days) at the 5th week. Gerbils were evaluated at the 12th, 24th and 48th weeks. Results: In the Hp group, all gerbils were persistently infected for 24 weeks, but 36% became negative for H. pylori at the 48th week. In the Hp + RPZ group, 18% of gerbils at the 12th week, 40% at the 24th week, and 80% at the 48th week, became negative for H. pylori. The level of neutrophil infiltration was significantly decreased in the Hp + RPZ group in comparison to the Hp group, possibly through the effects of RPZ on initial bacterial colonization and resultant inflammation. Even in the gerbils that became H. pylori -negative, the level of neutrophil infiltration was lower in the Hp + RPZ group than in the Hp group. RPZ treatment significantly increased the level of the reduced form of glutathione (GSH) at the 48th week. The elevated levels of the reduced form of GSH may have been reduced by an antioxidation process in the H. pylori -positive Hp + RPZ group. Conclusion: Administration of RPZ not only inhibited gastric H. pylori colonization, but also reduced gastric mucosal inflammation in gerbils, possibly through its antibacterial action as well as pharmacological recruitment of the reduced form of GSH. © 2003 Blackwell Publishing Asia Pty Ltd [source] Pyloric gland metaplasia and pouchitis in patients with ileal pouch-anal anastomosesALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2010R. KARIV Aliment Pharmacol Ther,31, 862,873 Summary Background, Diagnosis and management of chronic antibiotic-refractory pouchitis and Crohn's disease of the pouch can be challenging. Pyloric gland metaplasia is a histological feature indicative of chronic mucosal inflammation. Its value in diagnosis and prognosis of pouch disorders has not been investigated. Aim, To assess the prevalence, diagnostic and prognostic value, and risk factors of pyloric gland metaplasia in pouch patients. Methods, Patients were identified from our prospectively maintained Pouchitis Database. Pouch biopsy specimens were re-reviewed for pyloric gland metaplasia and other histological features. Two cohorts of patients were studied: a historical cohort (n = 111) and the second, a validation cohort (n = 100). Univariate and multivariate analyses were performed to assess risk factors for pyloric gland metaplasia. Results, The prevalence of pyloric gland metaplasia in the historical cohort and validation cohort was 45 (40.1%) and 24 (24.0%), respectively. The sensitivity and specificity of pyloric gland metaplasia for the diagnosis of chronic antibiotic-refractory pouchitis or Crohn's disease were 70.7% and 92.5%, respectively, for the first cohort and 39.0% and 86.4%, respectively, for the 2nd validation cohort. In multivariate analysis of the first cohort, patients with refractory pouchitis or Crohn's disease were 28 times (95% CI, 7.3,107.1) more likely to have pyloric gland metaplasia than those with a normal pouch or irritable pouch syndrome. The factor of refractory pouchitis or Crohn's disease remained in the model for the 2nd validation cohort with odds ratio of 4.58 (95% CI, 1.6,13.4). Conclusions, Pyloric gland metaplasia is associated with diagnosis of chronic antibiotic-refractory pouchitis or Crohn's disease of the pouch and appears to be a specific marker for both disease entities. [source] Changes of gastric mucosal architecture during long-term omeprazole therapy: results of a randomized clinical trialALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2006L. LUNDELL Summary Background, The impact of long-term acid suppression on the gastric mucosa remains controversial. Aim, To report further observations on an established cohort of patients with gastro-oesophageal reflux disease, after 7 years of follow-up. Methods, Of the original cohort randomized to either antireflux surgery or omeprazole, 117 and 98 patients remained in the medical and surgical arms, respectively. Gastric biopsies were taken at baseline and throughout the study. Results, Fifty-three antireflux surgery and 39 omeprazole-treated patients had Helicobacter pylori infection at randomization. Eighty-three omeprazole-treated and 60 antireflux surgery patients remained H. pylori negative over the 7 years, and no change was observed in mucosal morphology except for a change in endocrine cell population (linear and diffuse hyperplasia, P = 0.03). During the 7-year study many patients, who were initially H. pylori infected, had the infection eradicated leaving only 13 omeprazole and 12 antireflux surgery patients still infected. In these patients, omeprazole induced a deterioration of the mucosal inflammation scores (P = 0.01) with a numerical increase of glandular atrophy. Conclusions, Long-term omeprazole therapy does not alter the exocrine oxyntic mucosal morphology in H. pylori -negative patients, but mucosal endocrine cells appear to be under proliferative stimulation; in H. pylori -positive patients there are changes in mucosal inflammation and atrophy. [source] Is clinical remission the optimum therapeutic goal in the treatment of Crohn's disease?ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2002I. D. R. Arnott Currently, the therapeutic end-point in the treatment of Crohn's disease is the remission of symptoms, but recent data confirm that mucosal inflammation may continue in the absence of symptoms. Furthermore, emerging evidence indicates that such subtle, sub-clinical mucosal inflammation leads to clinical relapse. The assessment of mucosal inflammation has become easier with the availability of faecal calprotectin assay. Current anti-inflammatory therapy often leaves low-grade mucosal inflammation untreated, and therefore recurrent relapses occur. We need to investigate whether the therapeutic end-point of anti-inflammatory medications needs to be more rigorous and to aim at complete mucosal healing, confirmed by the normalization of mucosal inflammatory markers such as faecal calprotectin concentrations. Immunosuppressive therapy with azathioprine/ 6-mercaptopurine currently offers the best mucosal healing treatment with reduction of relapses, but newer biological agents might offer less toxic therapy. Clinical trials to test the feasibility and efficacy of such a paradigm shift in the medical management of Crohn's disease are now warranted. [source] Polaprezinc attenuates the Helicobacter pylori -induced gastric mucosal leucocyte activation in Mongolian gerbils,a study using intravital videomicroscopyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2001H. Suzuki Background: We previously demonstrated that Helicobacter pylori colonization evokes gastric mucosal inflammation and an extensive increase in lipid peroxides and glutathione in Mongolian gerbils. Zinc and its derivative, polaprezinc, have been reported to be potent antioxidants in gastric mucosa. Aim: To examine the effect of polaprezinc on gastric mucosal oxidative inflammation in H. pylori -colonized Mongolian gerbils. Methods: Sixty-eight male Mongolian gerbils were orally inoculated with H. pylori (ATCC43504, 5 × 108 CFUs/gerbil; H. pylori group) and 35 gerbils were inoculated with the culture media (control group). Twenty-two gerbils in the H. pylori and 13 gerbils in the control group were fed with diets containing polaprezinc (0.06%, 100 mg/kg, 10 times the usual clinical dose) (H. pylori + polaprezinc group, polaprezinc group). The remaining gerbils were fed a standard laboratory chow diet. Neutrophil infiltration, assessed histologically and by the activity of myeloperoxidase, the contents of CXC-chemokine (GRO/CINC-1-like protein) and the contents of thiobarbituric acid-reactive substances, was evaluated in each group 12 weeks after the inoculation. Separately, gastric mucosal leucocyte activation and capillary perfusion were also assessed using intravital microscopy 2, 4, 8 and 12 weeks after the inoculation. Results: In all H. pylori -inoculated animals, the bacterial infection persisted throughout the experimental period. Gastric mucosal lesion formation in the H. pylori group was significantly inhibited in the H. pylori + polaprezinc group. Elevated levels of myeloperoxidase activity, GRO/CINC-1 and thiobarbituric acid-reactive substances in the H. pylori group at 12 weeks were attenuated significantly by polaprezinc treatment. Enhanced levels of venular leucocyte activation observed in the H. pylori group were attenuated significantly in the H. pylori + polaprezinc group during both the early phase (2 weeks) and late phase (12 weeks). Conclusion: Polaprezinc inhibited H. pylori -associated gastric mucosal oxidative inflammation, including initial micro-vascular leucocyte activation, in Mongolian gerbils. [source] Important research questions in allergy and related diseases: 3-chronic rhinosinusitis and nasal polyposis , a GA2LEN studyALLERGY, Issue 4 2009C. Bachert Chronic rhinosinusitis is one of the most common health care challenges, with significant direct medical costs and severe impact on lower airway disease and general health outcomes. The diagnosis of chronic rhinosinusitis (CRS) currently is based on clinical signs, nasal endoscopy and CT scanning, and therapeutic recommendations are focussing on 2 classes of drugs, corticosteroids and antibiotics. A better understanding of the pathogenesis and the factors amplifying mucosal inflammation therefore seems to be crucial for the development of new diagnostic and therapeutic tools. In an effort to extend knowledge in this area, the WP 2.7.2 of the GA2LEN network of excellence currently collects data and samples of 1000 CRS patients and 250 control subjects. The main objective of this project is to characterize patients with upper airway disease on the basis of clinical parameters, infectious agents, inflammatory mechanisms and remodeling processes. This collaborative research will result in better knowledge on patient phenotypes, pathomechanisms, and subtypes in chronic rhinosinusitis. This review summarizes the state of the art on chronic rhinosinusitis and nasal polyposis in different aspects of the disease. It defines potential gaps in the current research, and points to future research perspectives and targets. [source] IL1,- and LPS-induced serotonin secretion is increased in EC cells derived from Crohn's diseaseNEUROGASTROENTEROLOGY & MOTILITY, Issue 4 2009M. Kidd Abstract, Gut mucosal enterochromaffin (EC) cells are regarded as key regulators of intestinal motility and fluid secretion via secretion of serotonin (5HT), are increased in numbers in mucosal inflammation and located in close proximity to immune cells. We examined whether interleukin (IL)1, and Escherichia coli lipopolysaccharide (LPS) induced EC cell 5HT release through Toll-like/IL-1 (TIL) receptor activation, nuclear factor kappa B (NF,B) and mitogen-activated protein kinase (MAPK) phosphorylation and evaluated whether somatostatin could inhibit this phenomenon. Pure (>98%) human intestinal EC cells were isolated by fluorescent activated cell sorting from preparations of normal (n = 5) and Crohn's colitis (n = 6) mucosa. 5HT release was measured (ELISA), and NF,B and ERK phosphorylation quantitated (ELISA) in response to IL1, and LPS. 5HT secretion was increased by both E. coli LPS (EC50 = 5 ng mL,1) and IL1, (EC50 = 0.05 pmol L,1) >2-fold (P < 0.05) in Crohn's EC cells compared with normal EC cells. Secretion was reversible by the TLR4 antagonist, E. coli K12 LPS (IC50 = 12 ng mL,1) and the IL1, receptor antagonist (ILRA; IC50 = 3.4 ng mL,1). IL1, caused significant (P < 0.05) NF,B and MAPK phosphorylation (40,55%). The somatostatin analogue, lanreotide inhibited IL1,-stimulated secretion in Crohn's (IC50 = 0.61 nmol L,1) and normal EC cells (IC50 = 1.8 nmol L,1). Interleukins (IL1,) and bacterial products (E. coli LPS) stimulated 5HT secretion from Crohn's EC cells via TIL receptor activation (TLR4 and IL1,). Immune-mediated alterations in EC cell secretion of 5HT may represent a component of the pathogenesis of abnormal bowel function in Crohn's disease. Inhibition of EC cell-mediated 5HT secretion may be an alternative therapeutic strategy in the amelioration of inflammatory bowel disease symptomatology. [source] Long-lasting changes in small intestinal transport following the recovery from Trichinella spiralis infectionNEUROGASTROENTEROLOGY & MOTILITY, Issue 3 2006K. Venkova Abstract, Changes in intestinal motility and visceral sensitivity are found after resolution of acute enteric inflammation. The study investigates whether a transient nematode-induced intestinal inflammation may result in long-lasting remodelling of epithelial transport. Ferrets infected with Trichinella spiralis or sham-infected animals were euthanized on day 10, 30 or 60 postinfection (PI) and the jejunum was isolated. The net transport of electrolytes was measured electrophysiologically as transmucosal short-circuit current (Isc) and responses to electrical field stimulation (EFS: 1,32 Hz) or secretagogues were investigated. Myeloperoxidase (MPO) activity, a marker of mucosal inflammation, was maximal during the enteric stage of T. spiralis infection (day 10 PI) and returned to normal on days 30 and 60 PI. Mucosal inflammation caused a reduction in basal Isc, increased electrical conductance (G) and decreased the maximal responses to EFS, carbachol or histamine. On days 30 and 60 PI the inflammation resolved and basal electrogenic transport appeared normal; however, the secretion induced by EFS, carbachol or histamine remained suppressed. Moreover, EFS-induced responses were shifted from predominantly cholinergic in controls to non-cholinergic in the infected animals. The results suggest that a transient small intestinal inflammation causes a long-term remodelling of epithelial function. [source] Steroid-sensitive indices of airway inflammation in children with seasonal allergic rhinitisPEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 1 2003Peter Meyer Previous studies involving adults have demonstrated that airway glucocorticosteroids inhibit plasma exudation and eosinophil activity in allergic rhinitis. This study explores the possibility that plasma exudation, exudative responsiveness, and the occurrence of eosinophil activity-related proteins are glucocorticosteroid-sensitive nasal mucosal indices in allergic children. Using a placebo-controlled, parallel-group design effects of nasal budesonide (64 µg per nasal cavity b.i.d) were determined in children with seasonal allergic rhinitis. Nasal lavage fluid levels of eotaxin, eosinophil cationic protein (ECP), and ,2 -macroglobulin, indicating plasma exudation, were determined, the latter with and without challenge with topical histamine. Nasal lavage fluid levels of ,2 -macroglobulin and ECP increased significantly during the pollen season, and the acute plasma exudation response to histamine was significantly greater during than outside the season. There was a trend towards a seasonal increase in nasal lavage fluid levels of eotaxin. Budesonide significantly inhibited the seasonal increase in ,2 -macroglobulin as well as the exudative hyperresponsiveness to histamine. Any tendency of increases in mucosal output of eotaxin and ECP was abolished by the glucocorticosteroid treatment. We conclude that mucosal exudation of plasma, as a global sign of active inflammatory processes, is a glucocorticosteroid-sensitive facet of allergic rhinitis in children. Exudative hyperresponsiveness, potentially caused by several weeks of mucosal inflammation, emerges as a significant feature of allergic rhinitis in children, and its development is prevented by local treatment with a glucocorticosteroid drug. The seasonal increase in ECP and the trend for an increase in eotaxin were absent in the glucocorticosteroid-treated subjects. [source] Prostaglandin E2 is activated by airway injury and regulates fibroblast cytoskeletal dynamics,THE LARYNGOSCOPE, Issue 7 2009Vlad C. Sandulache MD Abstract Objectives/Hypothesis: To characterize the activation of cyclooxygenase (COX)-2/prostaglandin (PG) E2 signaling during airway mucosal repair and its subsequent role during the wound healing process. Study Design: Prospective animal study. Methods: The subglottis was approached via cricothyroidotomy. Sham airways were closed, and wounded airways were subjected to laser injury and closed. Subglottic tissue was harvested at 12 hours, 24 hours, 48 hours, and 72 hours postinjury. Secretions were collected preoperatively and at time of sacrifice. Inflammatory gene expression was analyzed using quantitative reverse transcriptase polymerase chain reaction. Subglottic/tracheal explants were exposed to exogenous IL-1, in the presence or absence of COX inhibitors. Explant-produced PGE2 levels were assayed using enzyme linked immunoassays. Human airway fibroblast migration and collagen contraction were assayed in the presence or absence of prostaglandin E2. Results: Laser injury triggers a rapid, dose-dependent increase in mucosal IL-1, and COX-2 gene expression, with an anatomical distribution proportional to the distance from the site of injury. Gene upregulation correlates with dose-dependent increases in PGE2 mucosal secretion levels. Ex vivo analysis indicates IL-1, is responsible for the activation of the COX-2 / PGE2 pathway. Prostaglandin E2 differentially inhibits airway fibroblast migration and contraction in a specific, dose-dependent manner. Conclusions: PGE2 is activated during mucosal inflammation and acts to decrease fibroplastic activity in the mucosal wound bed. During subglottic stenosis (SGS) development, the levels of PGE2 generated in response to injury may be insufficient to blunt the intrinsically fibroplastic phenotype of SGS fibroblasts, resulting in excessive scarring. Laryngoscope, 2009 [source] | ||||||||||||||||||||||||||||