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Mucosal Tissue (mucosal + tissue)
Selected AbstractsStrategies for optimizing targeting and delivery of mucosal HIV vaccinesEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 10 2009Jeffrey D. Ahlers Abstract Effective frontline defenses against HIV-1 will require targeting vaccines to mucosal tissue in order to induce ,, CD8+ lymphocytes in mucosal effector sites (lamina propria and intraepithelial compartment) as well as antibody secreting plasma cells that can neutralize and limit free virus. A concerted second wave of assault against the virus will require the activation and recruitment of antigen specific memory CD4+ and CD8+ T cells in mesenteric lymph nodes and distal secondary lymphoid organs. New delivery strategies targeting the "right" DC subsets in combination with delivery of mucosal adjuvants and innate signals for activating DC will be essential for mucosal vaccines in order to circumvent the naturally tolerogenic environment and the induction of Tregs. Mucosal delivery of antigen in combination with inflammatory signals has been shown to empower systemic immunization by directing responses to mucosal sites for imprinting optimum mucosal memory. Here, we discuss novel vaccine strategies and adjuvants for optimizing mucosal delivery of HIV vaccines. [source] Runt-related transcription factor 3 is associated with ulcerative colitis and shows epistasis with solute carrier family 22, members 4 and 5INFLAMMATORY BOWEL DISEASES, Issue 12 2008Rinse K. Weersma MD Abstract Background: Inflammatory bowel disease (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), are intestinal inflammatory disorders with a complex genetic background. Mice deficient for the runt-domain-transcription-factor3 (Runx3) develop spontaneous colitis. Human RUNX3 resides in an IBD-susceptibility locus. We studied the association of RUNX3 in a cohort of IBD patients and analyzed the interaction with SLC22A4/5. RUNX3 and OCTN1 mRNA expression was assessed in inflamed and noninflamed mucosa from patients and controls. Methods: 543 IBD patients (309 CD / 234 UC) and 296 controls were included. Four single nucleotide polymorphisms (SNPs) and 4 microsatellite markers were studied for RUNX3. Five SNPs (including SNP-207G,C and SNP1672C,T) were analyzed for SLC22A4/5. RUNX3, and OCTN1 expression in mucosal tissue from 30 patients (14 UC / 16 CD) and 6 controls were determined by quantitative polymerase chain reaction. Results: A significant association between RUNX3 -SNP rs2236851 and UC (OR 1.61; 95% confidence interval [CI] 1.11,2.32, P = 0.020) was found. Carriership is associated with pancolitis (odds ratio [OR] 1.86; 95% CI 1.08,3.21). SLC22A4/5 -SNPs rs272893 and rs273900 are associated with CD (OR 2.16; 95% CI 1.21,3.59 and OR 2.40; 95% CI 1.43,4.05). We found epistasis for carriership of a risk-associated allele in RUNX3 and SLC22A4/5 for UC patients versus CD patients (OR 3.83; 95% CI 1.26,11.67). RUNX3 mRNA expression is increased (P = 0.01) in inflamed colonic mucosa of UC patients compared to noninflamed mucosa and controls. Conclusions: We provide evidence for the genetic association of RUNX3 with UC and for CD with the IBD5 locus including SLC22A4/5. An epistatic effect of RUNX3 and SLC22A4 was associated with an increased risk for UC. Our data suggest a role for RUNX3 in UC susceptibility. (Inflamm Bowel Dis 2008) [source] Prediction of jet flows in the supersonic nozzle and diffuserINTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN FLUIDS, Issue 10-11 2005Yi Liu Abstract The authors' recently-developed code for a needle-free powdered vaccine delivery device, the epidermal powdered inject system (EPI), is summarized in this paper. The behaviour of supersonic jet flows, which accelerate micron sized powdered vaccines to penetrate human skin or mucosal tissue, is therefore of great importance. A well-established modified implicit flux vector splitting (MIFVS) solver for the Navier,Stokes equations is extended to study numerically the transient supersonic jet flows of interest. A low Reynolds number k,, turbulence model, with the compressibility effect considered, is integrated into MIFVS solver to predict the turbulent structures and interactions with inherent shock systems. The results for the NASA validation case NPARC, Venturi and contoured shock tube (CST) of the EPI system are discussed. Copyright © 2005 John Wiley & Sons, Ltd. [source] Protective effect of glucosamine against ibuprofen-induced peptic ulcer in ratsJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 6 2007Sethumadhavan Santhosh Abstract Background:,Helicobacter pylori is the major causative factor of ulcer but the use of ibuprofen and other non-steroidal anti-inflammatory drugs have also been implicated in development of ulcer. The purpose of the present study was to determine the anti-ulcer effect of glucosamine. Methods:, The protective effect of glucosamine on ibuprofen-induced peptic ulcer in male albino rats was studied with respect to changes in the volume of gastric juice, acid output, pepsin activity, activities of membrane bound ATPases, protein content, glycoprotein components and histopathology. Results:, Oral administration of ibuprofen caused significant increase in the number of lesions in the gastric mucosa, increases in the volume of gastric juice and acidity, and decreased activity of pepsin. The levels of protein content and glycoprotein components (hexose, hexosamine and sialic acid) and ATPase activities were also observed. Oral pretreatment with glucosamine resulted in significant reduction in the number of lesions in the gastric mucosa and decreases in the volume of gastric juice and acidity. The pepsin activity was also maintained at near normalcy. Prior oral administration of glucosamine significantly prevented the ibuprofen-induced depletion of protein and glycoprotein components and maintained the activities of membrane bound ATPases as compared to untreated ulcer induced group of rats. Conclusion:, The anti-ulcerogenic activity of glucosamine might be ascribable to its ability to neutralize the hydrochloric acid secreted into the stomach and to its capability to strengthen the mucosal barrier by increasing mucosal glycoprotein synthesis and to its free radical scavenging property. Histopathological investigations of the mucosal tissue also support the anti-ulcerogenic effect of glucosamine. [source] Gene expression profiling of gut mucosa and mesenteric lymph nodes in simian immunodeficiency virus-infected macaques with divergent disease courseJOURNAL OF MEDICAL PRIMATOLOGY, Issue 4-5 2006M.D. George Abstract Background, Although the majority of drug-naïve HIV-infected patients develop acquired immunodeficiency syndrome (AIDS), a small percentage remains asymptomatic without therapeutic intervention. Methods, We have utilized the simian immunodeficiency virus (SIV)-infected rhesus macaque model to gain insights into the molecular mechanisms of long-term protection against simian AIDS. Results, Chronically SIV-infected macaques with disease progression had high viral loads and CD4+ T-cell depletion in mucosal tissue and peripheral blood. These animals displayed pathologic changes in gut-associated lymphoid tissue (GALT) and mesenteric lymph node that coincided with increased expression of genes associated with interferon induction, inflammation and immune activation. In contrast, the animal with long-term asymptomatic infection suppressed viral replication and maintained CD4+ T cells in both GALT and peripheral blood while decreasing expression of genes involved in inflammation and immune activation. Conclusions, Our findings suggest that reduced immune activation and effective repair and regeneration of mucosal tissues correlate with long-term survival in SIV-infected macaques. [source] Pharmaceutical applications of mucoadhesion for the non-oral routesJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 1 2005Katarina Edsman The adhesion of pharmaceutical formulations to the mucosal tissue offers the possibility of creating an intimate and prolonged contact at the site of administration. This prolonged residence time can result in enhanced absorption and, in combination with a controlled release of the drug, also improved patient compliance by reducing the frequency of administration. During the almost 30 years over which mucoadhesion has been studied, a considerable amount of knowledge has been gained, and much has been learned about the different mechanisms occurring at the formulation-mucus interface and the properties that affect these mechanisms. The in-vivo performance of a dosage form not only depends on the mechanisms occurring at the interface, but also on the properties of the total mucoadhesive complex: the dosage form, the mucosa and the interface between them. A wide variety of methods are used for studying mucoadhesion; some rather similar to the in-vivo situation and some mimicking the interface alone. In this review, the mucus surface, the methods used for the study of mucoadhesion, the different mechanisms involved in mucoadhesion and theories underpinning them have been described. The complexity of mucoadhesion when trying to systemize the subject will also be discussed. The last part of the review describes the buccal, nasal, ocular, vaginal and rectal routes and provides examples of what can be achieved in-vivo when using mucoadhesive formulations. [source] A detailed assessment of the pattern of moxidectin tissue distribution after pour-on treatment in calvesJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2003J. M. Sallovitz The use of topical (pour-on) administration of endectocide drugs in cattle has reached world-wide acceptance. However, only limited information is available on the kinetic behaviour for topically administered moxidectin (MXD). To improve our understanding of the relationship between pharmacokinetics and efficacy for pour-on preparations, MXD concentration profiles were measured in tissues of endo- and ectoparasites location over 35 days postadministration. MXD distribution to the fluid content and mucosal tissue of the abomasum and different intestinal sections (duodenum, ileum, caecum and colon) was assessed. The comparative patterns of MXD distribution to skin and hypodermic tissue from different anatomical sites (backline, rib cage, thigh and face) were also investigated following the pour-on administration. Wide tissue distribution and long residence time characterized the kinetics of topically administered MXD. MXD was recovered between 1 and 35 days post-treatment in all the tissues investigated. The highest MXD availabilities were observed in the skin layers at the site of administration (backline) and in the fat tissue. The fluid contents of different intestinal sections showed MXD concentrations higher than those measured in their respective mucosal tissues, particularly at day 1 post-treatment. MXD concentrations in the skin (epidermis + dermis) were higher than those measured in the hypodermic tissue. Large differences in the availability of MXD in skin from different anatomical regions (backline > rib cage > thigh > face) were observed. The low plasma and the high skin availability indicate the formation of a skin depot of the drug, being released slowly to the plasma and reaching concentrations in systemic tissues (abomasal mucosa, lungs, etc.) similar to those measured after subcutaneous administration. These findings demonstrate that target parasites may be exposed to markedly different drug concentrations according to their location sites, which is particularly relevant for ectoparasites located in different anatomical regions. Knowledge of the tissue distribution of topically administered endectocides contributes to understand the differences observed in efficacy and/or persistence of activity and to optimize their use in cattle. [source] Induction of immune responses and prevention of alveolar bone loss by intranasal administration of mice with Porphyromonas gingivalis fimbriae and recombinant cholera toxin B subunitMOLECULAR ORAL MICROBIOLOGY, Issue 6 2007Y. Takahashi Introduction:, Adult periodontitis is initiated by specific periodontal pathogens represented by Porphyromonas gingivalis; however, an effective measure for preventing the disease has not yet been established. In this study, the effectiveness of a vaccine composed of fimbriae of P. gingivalis and recombinant cholera toxin B subunit (rCTB) was evaluated using BALB/c mice. Methods:, Fimbriae and rCTB were co-administered intranasally to BALB/c mice on days 0, 14, 21, and 28. On day 35, mice were sacrificed to determine immunoglobulin levels in serum, saliva, and nasal and lung extracts by enzyme-linked immunosorbent assay. The prevention effect of the vaccine on P. gingivalis -induced periodontitis in mice was evaluated by measuring alveolar bone loss. Results:, The rCTB significantly increased serum immunoglobulin (Ig)A levels when mice were administered with a minimal amount (0.5 ,g) of the fimbrial antigen. The adjuvant effect on serum IgG production was indistinct because the minimal amount of the antigen still induced a large amount of IgG. In contrast to systemic responses, a fimbria-specific secretory IgA response was strongly induced by co-administration of rCTB and 0.5 ,g fimbriae; the same amount of the antigen alone scarcely induced a response. Histopathological examination revealed IgA-positive plasma cells in the nasal mucosal tissue but no observable mast cells in the area. In addition, nasal administration of the fimbrial vaccine significantly protected the mice from P. gingivalis -mediated alveolar bone loss. Conclusion:, Nasal vaccination with a combination of fimbriae and rCTB can be an effective means of preventing P. gingivalis -mediated periodontitis. [source] Infection of human mucosal tissue by Pseudomonas aeruginosa requires sequential and mutually dependent virulence factors and a novel pilus-associated adhesinCELLULAR MICROBIOLOGY, Issue 8 2010Ryan W. Heiniger Summary Tissue damage predisposes humans to life-threatening disseminating infection by the opportunistic pathogen Pseudomonas aeruginosa. Bacterial adherence to host tissue is a critical first step in this infection process. It is well established that P. aeruginosa attachment to host cells involves type IV pili (TFP), which are retractile surface fibres. The molecular details of attachment and the identity of the bacterial adhesin and host receptor remain controversial. Using a mucosal epithelium model system derived from primary human tissue, we show that the pilus-associated protein PilY1 is required for bacterial adherence. We establish that P. aeruginosa preferentially binds to exposed basolateral host cell surfaces, providing a mechanistic explanation for opportunistic infection of damaged tissue. Further, we demonstrate that invasion and fulminant infection of intact host tissue requires the coordinated and mutually dependent action of multiple bacterial factors, including pilus fibre retraction and the host cell intoxication system, termed type III secretion. Our findings offer new and important insights into the complex interactions between a pathogen and its human host and provide compelling evidence that PilY1 serves as the principal P. aeruginosa adhesin for human tissue and that it specifically recognizes a host receptor localized or enriched on basolateral epithelial cell surfaces. [source] Effect of mucosal and systemic immunization with virus-like particles of severe acute respiratory syndrome coronavirus in miceIMMUNOLOGY, Issue 2 2010Baojing Lu Summary Nasal administration has emerged as a promising and attractive route for vaccination, especially for the prophylaxis of respiratory diseases. Our previous studies have shown that severe acute respiratory syndrome coronavirus (SARS-CoV) virus-like particles (VLPs) can be assembled using a recombinant baculovirus (rBV) expression system and such VLPs induce specific humoral and cellular immune responses in mice after subcutaneous injection. Here, we investigated mucosal immune responses to SARS-CoV VLPs in a mouse model. Mice were immunized in parallel, intraperitoneally or intranasally, with VLPs alone or with VLPs plus cytosine,phosphate,guanosine (CpG). Immune responses, including the production of SARS-CoV-specific serum immunoglobulin G (IgG) and secretory immunoglobulin A (sIgA), were determined in mucosal secretions and tissues. Both immunizations induced SARS-CoV-specific IgG, although the levels of IgG in groups immunized via the intraperitoneal (i.p.) route were higher. sIgA was detected in saliva in groups immunized intranasally but not in groups immunized intraperitoneally. CpG had an adjuvant effect on IgA production in genital tract washes when administered intranasally but only affected IgA production in faeces samples when administered intraperitoneally. In addition, IgA was also detected in mucosal tissues from the lung and intestine, while CpG induced an increased level of IgA in the intestine. Most importantly, neutralization antibodies were detected in sera after i.p. and intranasal (i.n.) immunizations. Secretions in genital tract washes from the i.n. group also showed neutralization activity. Furthermore, VLPs that were administered intraperitoneally elicited cellular immune responses as demonstrated by enzyme-linked immunospot (ELISPOT) assay analyses. In summary, our study indicates that mucosal immunization with rBV SARS-CoV VLPs represent an effective means for eliciting protective systemic and mucosal immune responses against SARS-CoV, providing important information for vaccine design. [source] The impact of successive infections on the lung microenvironmentIMMUNOLOGY, Issue 4 2007Arnaud Didierlaurent Summary The effect of infection history on the immune response is ignored in most models of infectious disease and in preclinical vaccination studies. No one, however, is naïve and repeated microbial exposure, in particular during childhood, shapes the immune system to respond more efficiently later in life. Concurrent or sequential infections influence the immune response to secondary unrelated pathogens. The involvement of cross-reactive acquired immunity, in particular T-cell responses, is extensively documented. In this review, we discuss the impact of successive infections on the infected tissue itself, with a particular focus on the innate response of the respiratory tract, including a persistent alteration of (1) epithelial or macrophage expression of Toll-like receptors or adherence molecules used by subsequent bacteria to invade the host, (2) the responsiveness of macrophages and neutrophils and (3) the local cytokine milieu that affects the activation of local antigen-presenting cells and hence adaptive immunity to the next infection. We emphasize that such alterations not only occur during coinfection, but are maintained long after the initial pathogen is cleared. As innate responses are crucial to the fight against local pathogens but are also involved in the maintenance of the homeostasis of mucosal tissues, dysregulation of these responses by repeated infections is likely to have a major impact on the outcome of infectious or allergic disease. [source] Rebamipide enema therapy as a treatment for patients with active distal ulcerative colitisJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 2 2007Ryuichi Furuta Background:, The clinical efficacy of corticosteroids in the treatment of ulcerative colitis (UC) is well-established. However, prolonged usage of these drugs can result in serious complications. Rebamipide {2-(4-chlorobenzoylamino)-3[2-(1H)-quinolinon-4-yl] propionic acid}, a cytoprotective agent, has been reported to have anti-inflammatory activity and to repair mucosal injury in animal colitis models. The aim of the present study was to assess the clinical efficacy and safety of a novel Rebamipide enema therapy in UC patients. Methods:, Twenty patients with the active distal type of UC in whom corticosteroid treatment had been unsuccessful were treated with rectal administration of Rebamipide twice a day for 3 weeks, during which corticosteroid dosage was kept constant. The efficacy of treatment was assessed from clinical symptoms and endoscopic findings. The anti-inflammatory effect of Rebamipide was also examined by monitoring changes in the intensity of histological inflammation and levels of cytokine activity in the rectal mucosa. Results:, At 3 weeks after the initiation of Rebamipide enema therapy, 11 patients (55%) achieved clinical remission. Sixteen (80%) were colonoscopically judged to be responders, with decreased levels of interleukin (IL)-1, but not of IL-8, and an increased ratio of IL-1 receptor antagonist/IL-1, in organ cultures of mucosal tissues. The change in the number of infiltrating neutrophils was not significantly correlated with the clinical response to this therapy. No side-effects were noted in any patients. Conclusion:, Rebamipide enema therapy proved to be safe and useful in corticosteroid-refractory patients with the active distal type of UC. [source] Developing an HIV cytotoxic T-lymphocyte vaccine: issues of CD8 T-cell quantity, quality and locationJOURNAL OF INTERNAL MEDICINE, Issue 1 2009D. Masopust Abstract. Issues of quantity, quality and location impact the ability of CD8 T cells to mediate protection from infection. These issues are considered in light of human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) vaccination. Methods are reviewed that result in 100- to 1000-fold higher frequencies of vaccine-specific memory CD8 T cells than that achieved by current HIV/SIV vaccine approaches. Data demonstrating that location within mucosal tissues has a direct impact on memory CD8 T-cell function are discussed. Arguments are made that establishing memory CD8 T cells within mucosal sites of transmission, a priori to natural infection, may be essential for conferring optimal and rapid protection. Lastly, it is proposed that heterologous prime-boost vaccination with recombinant live replicating vectors, which has the potential to induce tremendous numbers of cytolytic memory CD8 T cells within mucosal tissues, would provide a far more stringent test of the hypothesis that memory CD8 T cells could, in principal, form the basis for a preventative HIV vaccine. [source] Gene expression profiling of gut mucosa and mesenteric lymph nodes in simian immunodeficiency virus-infected macaques with divergent disease courseJOURNAL OF MEDICAL PRIMATOLOGY, Issue 4-5 2006M.D. George Abstract Background, Although the majority of drug-naïve HIV-infected patients develop acquired immunodeficiency syndrome (AIDS), a small percentage remains asymptomatic without therapeutic intervention. Methods, We have utilized the simian immunodeficiency virus (SIV)-infected rhesus macaque model to gain insights into the molecular mechanisms of long-term protection against simian AIDS. Results, Chronically SIV-infected macaques with disease progression had high viral loads and CD4+ T-cell depletion in mucosal tissue and peripheral blood. These animals displayed pathologic changes in gut-associated lymphoid tissue (GALT) and mesenteric lymph node that coincided with increased expression of genes associated with interferon induction, inflammation and immune activation. In contrast, the animal with long-term asymptomatic infection suppressed viral replication and maintained CD4+ T cells in both GALT and peripheral blood while decreasing expression of genes involved in inflammation and immune activation. Conclusions, Our findings suggest that reduced immune activation and effective repair and regeneration of mucosal tissues correlate with long-term survival in SIV-infected macaques. [source] A detailed assessment of the pattern of moxidectin tissue distribution after pour-on treatment in calvesJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2003J. M. Sallovitz The use of topical (pour-on) administration of endectocide drugs in cattle has reached world-wide acceptance. However, only limited information is available on the kinetic behaviour for topically administered moxidectin (MXD). To improve our understanding of the relationship between pharmacokinetics and efficacy for pour-on preparations, MXD concentration profiles were measured in tissues of endo- and ectoparasites location over 35 days postadministration. MXD distribution to the fluid content and mucosal tissue of the abomasum and different intestinal sections (duodenum, ileum, caecum and colon) was assessed. The comparative patterns of MXD distribution to skin and hypodermic tissue from different anatomical sites (backline, rib cage, thigh and face) were also investigated following the pour-on administration. Wide tissue distribution and long residence time characterized the kinetics of topically administered MXD. MXD was recovered between 1 and 35 days post-treatment in all the tissues investigated. The highest MXD availabilities were observed in the skin layers at the site of administration (backline) and in the fat tissue. The fluid contents of different intestinal sections showed MXD concentrations higher than those measured in their respective mucosal tissues, particularly at day 1 post-treatment. MXD concentrations in the skin (epidermis + dermis) were higher than those measured in the hypodermic tissue. Large differences in the availability of MXD in skin from different anatomical regions (backline > rib cage > thigh > face) were observed. The low plasma and the high skin availability indicate the formation of a skin depot of the drug, being released slowly to the plasma and reaching concentrations in systemic tissues (abomasal mucosa, lungs, etc.) similar to those measured after subcutaneous administration. These findings demonstrate that target parasites may be exposed to markedly different drug concentrations according to their location sites, which is particularly relevant for ectoparasites located in different anatomical regions. Knowledge of the tissue distribution of topically administered endectocides contributes to understand the differences observed in efficacy and/or persistence of activity and to optimize their use in cattle. [source] Peri-operative management of a patient with hereditary angioedema undergoing laparoscopic cholecystectomyANAESTHESIA, Issue 1 2010A. Spyridonidou Summary Hereditary angioedema is a rare genetic disorder resulting from an inherited deficiency or dysfunction of the C1-esterase inhibitor of the classic complement pathway. It is characterised by recurrent episodes of angioedema, without urticaria or pruritus, most often affecting the skin or the mucosal tissues of the upper respiratory and gastrointestinal tracts. We describe the peri-operative care of a woman with hereditary angioedema undergoing laparoscopic cholecystectomy with emphasis on the role of anaesthetists as peri-operative physicians. [source] Suppressive activity of fexofenadine hydrochloride on metalloproteinase production from nasal fibroblasts in vitroCLINICAL & EXPERIMENTAL ALLERGY, Issue 12 2004K. Asano Summary Background Allergic rhinitis (AR) is an inflammatory disease characterized by nasal wall remodelling with intense infiltration of eosinophils and mast cells/basophils. Matrix metalloproteinases (MMPs), MMP-2 and MMP-9, are the major proteolytic enzymes that induce airway remodelling. These enzymes are also important in the migration of inflammatory cells through basement membrane components. Objective We evaluated whether fexofenadine hydrochloride (FEX), the carboxylic acid metabolite of terfenadine with selective H1 -receptor antagonist activity, could inhibit MMP production from nasal fibroblasts (NFs) in response to TNF-, stimulation in vitro. Methods NFs were established from nasal polyp-derived fibroblasts (PFs) taken from patients with AR. Nasal mucosal fibroblasts (MFs) were also induced from nasal mucosal tissues from septal deformity patients without allergy. PF and MF (2 × 105 cells/mL, each) were stimulated with TNF-, in the presence of various concentrations of FEX. After 24 h, culture supernatants were obtained and assayed for MMP-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 levels by ELISA. The influence of FEX on mRNA expression of MMPs and TIMPs in 4 h-cultured cells was also evaluated by real-time RT-PCR. Furthermore, nuclear factor-,B (NF-,B) activation in fibroblasts treated with FEX for 4 h was examined by ELISA. Results FEX at more than 350 ng/mL inhibited the production of MMP-2 and MMP-9 from both PF and MF in response to TNF-, stimulation, whereas TIMP-1 and TIMP-2 production was scarcely affected by FEX. FEX also inhibited MMP mRNA expression and NF-,B activation in PF and MF after TNF-, stimulation. Conclusion The present data suggest that the attenuating effect of FEX on MMP-2 and -9 production from NFs induced by inflammatory stimulation may underlie the therapeutic mode of action of the agent on allergic diseases, including AR. [source] | ||||||||||