Home About us Contact
|
Home About us Contact | ||
|
|
||
Gut Inflammation (gut + inflammation)
Selected AbstractsAngiopoietin-2 in experimental colitisINFLAMMATORY BOWEL DISEASES, Issue 6 2010Vijay C. Ganta PhD Abstract Background: The pathophysiology of inflammatory bowel disease (IBD) includes leukocyte infiltration, blood and lymphatic remodeling, weight loss and protein enteropathy. The roles of angiopoietin-2 (Ang-2) in initiating gut inflammation, leukocyte infiltration and angiogenesis are not well understood. Methods: Disease activity index, histopathological scoring, myeloperoxidase assay, immunohistochemistry and sodium dodecyl sulphate- polyacrylamide gel electrophoretic methods were employed in the present study to addess the roles of Ang-2 in experimental colitis. Results: Several important differences were seen in the development of experimental IBD in Ang-2,/, mice. Although weight change and disease activity differ only slightly in WT and Ang-2,/, + DSS treated mice, leukocyte infiltration, inflammation and blood and lymphatic vessel density is significantly attenuated compared to WT + DSS mice. Gut capillary fragility and water export (stool blood and form) appear significantly earlier in Ang-2,/, + DSS mice vs. WT. Colon lengths were also significantly reduced in Ang-2,/, and gut histopathology was less severe in Ang-2,/, compared to WT + DSS. Lastly, the decrease in serum protein content in WT + DSS was less severe in Ang-2,/, + DSS, thus protein losing enteropathy (PLE) a feature of IBD is relieved by Ang-2,/,. Conclusion: These data demonstrate that in DSS colitis, Ang-2 mediates inflammatory hemangiogenesis, lymphangiogenesis and neutrophil infiltration to reduce some, but not all clinical features of IBD. The implications for Ang-2 manipulation in the development of IBD and other inflammatory diseases and treatments involving Ang-2 are discussed. (Inflamm Bowel Dis 2009) [source] Association between blood flow and inflammatory state in a T-cell transfer model of inflammatory bowel disease in miceINFLAMMATORY BOWEL DISEASES, Issue 5 2010Norman R. Harris PhD Abstract Background: Adoptive transfer of naive T-lymphocyte subsets into lymphopenic mice initiates chronic gut inflammation that mimics several aspects of inflammatory bowel disease (IBD). Patients with IBD can have profound alterations in intestinal blood flow, but whether the same is true in the T-cell transfer model has yet to be determined. Methods: In the current study, chronic intestinal inflammation was induced in recombinase-activating gene-1-deficient (RAG,/,) mice by adoptive transfer of CD4+ T-lymphocytes obtained from interleukin-10 deficient (IL-10,/,) mice. Results: Four weeks later, widespread colonic inflammation was observed in the reconstituted recipients, in contrast to 2 control sets of mice injected with a different subset of lymphocytes or with vehicle alone. We observed that the resulting pathology induced in the reconstituted RAG,/, mice was divided distinctly into 2 subsets: 1 with blood flow near normal with very high inflammation scores, and the other with severely attenuated blood flow but with much lower signs of inflammation. Colonic and ileal blood flow rates in the latter subset of CD4+ mice averaged only ,30% compared to the mice with higher inflammation scores. The lower blood flow rates were associated with greatly reduced red blood cell concentrations in the tissue, suggesting a possible loss of vascular density. Conclusions: In this model of chronic intestinal inflammation, mild inflammation was associated with significant decreases in blood flow. Inflamm Bowel Dis 2009 [source] Fecal S100A12 and fecal calprotectin as noninvasive markers for inflammatory bowel disease in childrenINFLAMMATORY BOWEL DISEASES, Issue 3 2008Marc A. Sidler MD Abstract Background: Fecal calprotectin is a sensitive marker for gut inflammation. Recently, we have established that a related protein, S100A12, is elevated in the feces of children with inflammatory bowel disease (IBD). This may represent a specific and sensitive disease marker. The objective was to investigate the utility of fecal S100A12, in comparison to fecal calprotectin and standard inflammatory markers, as a screening marker for IBD in children with gastrointestinal symptoms. Methods: Stool samples were obtained from 61 children presenting with gastrointestinal symptoms requiring endoscopy. Fecal S100A12, calprotectin, and serum S100A12 levels were measured and correlated to final diagnosis and standard tests (ESR, CRP, platelet count, and albumin). Results: Children diagnosed with IBD (n = 31) had elevated fecal S100A12 (median 55.2 mg/kg) and calprotectin (median 1265 mg/kg) levels compared with the children without IBD (n = 30; S100A12: median 1.1 mg/kg, P < 0.0001; calprotectin: median 30.5 mg/kg; P < 0.0001). The sensitivity and specificity of fecal S100A12 (cutoff 10 mg/kg) for the detection of IBD were both 97%, whereas fecal calprotectin (cutoff 50 mg/kg) gave a sensitivity of 100% and a specificity of 67%. Conclusions: Both fecal markers were superior to the sensitivities and specificities of any standard inflammatory test. Both fecal S100A12 and calprotectin are sensitive markers of gastrointestinal inflammation, but fecal S100A12 provided exceptional specificity in distinguishing children with IBD from children without IBD. Fecal S100A12 is a simple, noninvasive test that can be used to screen and select children warranting further invasive and laborious procedures such as endoscopy for the investigation of their gastrointestinal symptoms. (Inflamm Bowel Dis 2007) [source] Local and systemic interleukin-18 and interleukin-18-binding protein in children with inflammatory bowel diseaseINFLAMMATORY BOWEL DISEASES, Issue 1 2008Steven T. Leach Abstract Background: Interleukin-18 (IL-18) is increased in the inflamed mucosa of patients with Crohn's disease (CD). The balance between this pleiotropic proinflammatory cytokine and its natural inhibitor, IL-18-binding protein (IL-18BP), may contribute to the pathogenesis of inflammatory bowel disease (IBD). Methods: Serum and mucosal biopsies were collected from children with IBD, from children with celiac disease, and from controls. Biopsies were maintained in culture for 24 hours, and supernatant was collected. Serum and supernatant IL-18 and IL-18BPa concentrations were measured by immunoassay. Disease activity score (PCDAI) and standard serum inflammatory markers (albumin, platelets, ESR, and CRP) were recorded. Results: Serum IL-18 was greater in children with CD (537 pg/mL) than in controls (335 pg/mL; P < 0.05) but not in children with ulcerative colitis (UC) or IBD type unclassified (IBDU). Mucosal IL-18 was greater in children with CD and UC/IBDU than in controls (P < 0.01). Serum IL-18BPa was increased in children with CD compared with that in controls (3.9 versus 2.6 ng/mL; P < 0.05), but was not elevated in children with UC/IBDU. Furthermore, calculated free-serum IL-18 was elevated in CD, but not UC/IBDU, compared with that in controls (P = 0.001). Total and free-serum IL-18 were elevated in severe CD relative to in mild/moderate disease. Conclusions: IL-18, produced in the colons of children with IBD, may contribute to local inflammatory changes. Systemic IL-18 level may be a useful indicator of gut inflammation. Furthermore, free IL-18 is greatly elevated in children with CD, suggesting that compensatory increases in IL-18BPa are insufficient. Further exploration of the role of this cytokine in the pathogenesis of IBD is now required. (Inflamm Bowel Dis 2007) [source] Oro-facial granulomatosis: Crohn's disease or a new inflammatory bowel disease?INFLAMMATORY BOWEL DISEASES, Issue 9 2005FRCP, Jeremy Sanderson MD Abstract Background: Oro-facial granulomatosis (OFG) is a rare chronic inflammatory disorder presenting characteristically with lip swelling but also affecting gingivae, buccal mucosa, floor of mouth, and a number of other sites in the oral cavity. Histologically, OFG resembles Crohn's disease (CD), and a number of patients with CD have oral involvement identical to OFG. However, the exact relationship between OFG and CD remains unknown. Methods: Thirty-five patients with OFG and no gut symptoms were identified from a combined oral medicine/gastroenterology clinic. All underwent a standardized assessment of the oral cavity and oral mucosal biopsy to characterize the number of sites affected and the type of inflammation involved. Hematological and biochemical parameters were also recorded. All 35 patients underwent ileocolonoscopy and biopsy to assess the presence of coexistent intestinal inflammation. Results: Ileal or colonic abnormalities were detected in 19/35 (54%) cases. From gut biopsies, granulomas were present in 13/19 cases (64%). An intestinal abnormality was significantly more likely if the age of OFG onset was less than 30 years (P = 0.01). Those with more severe oral inflammation were also more likely to have intestinal inflammation (P = 0.025), and there was also a correlation between the histologic severity of oral inflammation and the histologic severity of gut inflammation (P = 0.047). No relationship was found between any blood parameter and intestinal involvement. Conclusions: Endoscopic and histologic intestinal abnormalities are common in patients with OFG with no gastrointestinal symptoms. Younger patients with OFG are more likely to have concomitant intestinal involvement. In these patients, granulomas are more frequent in endoscopic biopsies than reported in patients with documented CD. OFG with associated intestinal inflammation may represent a separate entity in which granulomatous inflammation occurs throughout the gastrointestinal tract in response to an unknown antigen or antigens. [source] Signal transducers and activators of transcription 3 signaling pathway.INFLAMMATORY BOWEL DISEASES, Issue 2 2005An Essential Mediator of Inflammatory Bowel Disease, Other Forms of Intestinal Inflammation Abstract Crohn's disease (CD) and ulcerative colitis (UC), the two major forms of chronic inflammatory bowel disease (IBD), are characterized by mucosal immune cell activation that is driven by a cytokine imbalance. Several cytokines involved in IBD act through the activation of the signal transducers and activators of transcription (STAT) family. We investigated the activation of STAT3 in the mucosa of CD and UC patients, and evaluated whether this event is specific for IBD patients. Using immunofluorescence and immunoblotting, total and phosphorylated STAT3 levels were assessed in biopsy specimens, isolated lamina propria mononuclear cells, and peripheral blood mononuclear cells from patients with CD, UC, other forms of intestinal inflammation, and control subjects. Immunoblotting revealed phosphorylated STAT3 in mucosal biopsy specimens from patients with CD, UC, celiac disease, and acute self-limited colitis, but not in the normal mucosa of control subjects. In IBD patients, STAT3 activation was confined to actively inflamed areas. Accordingly, activated STAT3 was detected in isolated lamina propria mononuclear cells from inflamed IBD tissues, but not in peripheral blood mononuclear cells from control subjects or IBD patients. Immunofluorescence demonstrated that the sources of activated STAT3 were macrophages and T lymphocytes, but not neutrophils. STAT3 activation also was detected in T cells infiltrating the duodenal mucosa of celiac disease patients. We conclude that STAT3 signaling occurs in both CD and UC, where it is strictly confined to areas of active inflammation and is limited to infiltrating macrophages and T cells. The occurrence of STAT3 signaling in other acute and chronic intestinal inflammatory conditions suggests that, rather than a specific feature of IBD, it represents a fundamental signaling pathway that is shared by multiple forms of gut inflammation. [source] Nerve Growth Factor Secretion in Cultured Enteric Glia Cells is Modulated by Proinflammatory CytokinesJOURNAL OF NEUROENDOCRINOLOGY, Issue 11 2006G. B. T. Von Boyen The enteric nervous system is composed of neurones and glial cells. These enteric glia cells (EGC) appear to be essential for the maintenance of gut homeostasis and mucosal integrity. Neurotrophin nerve growth factor (NGF) also plays an important role for the gut integrity by regulating sensory and inflammatory processes in the intestines. Here, we demonstrate EGCs as one source of NGF and show increased levels of NGF mRNA/protein and tropomyosin receptor kinase A (TrkA) mRNA in cultured EGCs upon stimulation with proinflammatory cytokines and lipopolysaccharides. NGF is continuously secreted from cultured EGCs and proinflammatory cytokines and lipopolysaccharides stimulate the secretion of this neurotrophin in a time- and dose- dependent manner, whereas interleukin-4 had no effect on NGF expression. Furthermore, NGF secretion was sustained for more than 12 h after withdrawal of the proinflammatory cytokines, suggesting the involvement of transcriptional and/or translational processes. Thus, the release of proinflammatory cytokines can increase NGF secretion by EGCs and leads to a higher expression of TrkA in EGCs. NGF, in turn, can increase visceral sensitivity and, on the other hand, appears to improve gut inflammation. Therefore, NGF secreting EGCs may play a key role in modulating visceral sensitivity and might be involved in inflammatory processes of the gut. [source] Dietary fiber, low-molecular-weight food constituents and colo-rectal inflammation in animal models , A reviewMOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 10 2009Dieter Schrenk Abstract This review provides an overview over studies in experimental animals aimed at elucidating the influence of dietary constituents on colo-rectal inflammation. Human studies as well as in vitro investigations will not be covered. In experimental animals, a variety of chemical treatments and genetic modifications, lead to various types of gut inflammation. In a number of these models, there is good evidence for an anti-inflammatory action of dietary tocopherols, certain polyphenols, and curcumin at relatively high oral doses. It has also been established, that oral application of fats and oils rich in n-3 PUFAs and/or conjugated linoleic acid (CLA) can attenuate certain types of colitis in experimental animal models. While the effect of dietary calcium on experimental colitis is less clear, there are hints indicating that certain high-fiber diets or diets rich in digestion-resistant carbohydrates ("fiber") can attenuate experimental colitis in animals, although contradictory results have been reported. In summary, the anti-inflammatory potency of dietary constituents on colon inflammation in experimental animals seems to be rather limited. The reasons for this lack of activity seem to be manifold including pharmacokinetic limitations and intestinal degradation of the compounds, in particular insufficient local, i. e., intra- or sub-mucosal levels of the effective compounds, and general limitations of animal models. [source] The cannabinoid CB2 receptor: a good friend in the gutNEUROGASTROENTEROLOGY & MOTILITY, Issue 9 2007A. A. Izzo Abstract, Mammalian tissues express the cannabinoid 1 (CB1) receptor and the cannabinoid 2 (CB2) receptor, the latter being involved in inflammation and pain. In somatic nerve pathways, the analgesic effects of CB2 agonism are well documented. Two papers published in the Journal have provided evidence that CB2 receptor activation inhibits visceral afferent nerve activity in rodents. These exciting findings are discussed in the context of recent data highlighting the emerging role of CB2 receptor as a critical target able to counteract hypermotility in pathophysiological states, gut inflammation and possibly colon cancer. [source] Overexpression of interleukin-23, but not interleukin-17, as an immunologic signature of subclinical intestinal inflammation in ankylosing spondylitisARTHRITIS & RHEUMATISM, Issue 4 2009Francesco Ciccia Objective Subclinical gut inflammation is common in spondylarthritis, but the immunologic abnormalities underlying this process are undefined. Perturbation of the interleukin-23 (IL-23)/Th17 axis has emerged as a fundamental trigger of chronic inflammation. This study was undertaken to investigate the expression and tissue distribution of IL-23/Th17,related molecules in Crohn's disease (CD) and in subclinical gut inflammation in ankylosing spondylitis (AS). Methods Quantitative gene expression analysis of Th1/Th2 and IL-23/Th17 responses was performed in intestinal biopsy samples obtained from 12 patients with CD, 15 patients with AS, and 13 controls. IL-23 tissue distribution and identification of IL-23,producing cells were evaluated by immunohistochemistry. Results We demonstrated a strong and significant up-regulation of IL-23p19 transcripts in the terminal ileum in patients with AS and patients with CD. IL-23 was abundantly produced by infiltrating monocyte-like cells in inflamed mucosa from AS and CD patients. Notably, we also identified Paneth cells as a major source of IL-23 in patients with AS, patients with CD, and normal controls. Unlike CD, in AS patients, IL-23 was not associated with up-regulation of IL-17 and the IL-17,inducing cytokines IL-6 and IL-1,. Finally, while the Th1-related cytokines interferon-,, IL-12p35, and IL-27p28 were overexpressed only in CD patients, IL-4, IL-5, and STAT-6 were also significantly increased in AS patients. Conclusion Our findings indicate that overexpression of IL-23, but not IL-17, is a pivotal feature of subclinical gut inflammation in AS. Identification of resident Paneth cells as a pivotal source of IL-23 in physiologic and pathologic conditions strongly suggests that IL-23 is a master regulator of gut mucosal immunity, providing a pathophysiologic significance to the reported association between IL-23 receptor polymorphisms and intestinal inflammation. [source] B cells are involved in the modulation of pathogenic gut immune response in food-allergic enteropathyCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 2 2008C. R. Cardoso Summary Food enteropathies involve uncontrolled or hypersensitivity reactions to ingested nutrients and may result in IgE and T-helper type 2 (Th2) responses as in food allergy. However, the precise role of B cells in the development of food enteropathies remains uncertain. In this work, we used B cell-deficient mice (B KO) and a model of peanut sensitization to examine the involvement of B lymphocytes in the pathogenesis of food allergy. Results showed that priming of wild-type (WT) mice with peanut proteins induced specific IgG1 and IgE responses in serum, with edema, tissue destruction, epithelial exulceration and inflammatory infiltrate in the gut of sensitized and challenged (S + Peanut) WT animals. In contrast, there was no sera immunoglobulin detection and absence of tissue destruction in the gut of B KO mice, which presented moderate inflammatory infiltrate and villous enlargement after peanut challenge. These animals presented marked decrease in IL-4 and TNF-, and high levels of IL-10, TGF-,, IL-12p40 and IFN-, mRNA in the gut. Moreover, the expression of CCL5, CCL11 and CXCL1 was reduced in the gut of B KO mice, in contrast to elevated messages of CCL2 or similar detection of Th1-related chemokines in S + Peanut WT mice. Finally, we provided evidence that B cells are necessary to the development of food-related enteropathies and induction of gut inflammation during allergic reactions to food. [source] | ||||||||||