These results suggest that IL-8 in the esophageal mucosa may be involved in the pathogenesis of esophageal inflammation, including non-erosive GERD.

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Objective: Over-expression of matrix metalloproteinases (MMPs) can accelerate tissue destruction and disrupt subsequent tissue repair. A dextran sulfate sodium (DSS) colitis model was established to examine the effects of MMP inhibition, by an orally active MMP inhibitor ONO-4847, on colonic inflammation. Materials and methods: Acute colitis was induced in female BALB/c mice by giving 8 % DSS orally in drinking water for 7 days. The animals were randomized into groups receiving different concentrations of ONO-4847 or vehicle by oral gavage every day. mRNA levels of 4 MMPs and a tissue inhibitor of MMP (TIMP-1) were measured by RT-PCR in intestinal tissue isolated from mice after DSS administration. Colonic mucosal injury and inflammation were evaluated clinically, biochemically, and histologically. The clinical disease activity index (DAI), including body weight loss, stool consistency, and blood in feces, was examined. Moreover, mucosal tumor necrosis factor (TNF)-a and interferon (IFN)-g were determined by immunoassay. Results: The intestinal expression of MMP-3, -7, 9, and -12 and TIMP-1 mRNA was upregulated after DSS administration. Shortening of the colon was significantly reversed by ONO-4847 at a dose of 30 mg/kg. DAI in DSS-treated mice was significantly lower in the ONO-4847-treated mice compared with the control mice. Histological study also showed a reduced infiltration of inflammatory cells, especially neutrophils, and reducedmucosal cell disruption in ONO-4847-treated mice compared with the control mice. The increases in tissue-associated myeloperoxidase activity and thiobarbituric acid-reactive substances after DSS administration were both significantly inhibited by co-administration with ONO-4847. ONO-4847 also inhibited increases in the mucosal TNF-a and IFN-g content after DSS administration. Conclusion: Improvements in DSS colitis in response to ONO-4847 suggest that activation of MMPs contributes to the initiation/amplification of colonic inflammatory injury by mechanisms including oxidative damage as well as enhancement of inflammatory cytokine release.

These results indicate that a low dose of NM can inhibit the colonic mucosal inflammation induced by TNBS in rats, which suggests that anti-tryptase therapy using low doses of NM has excellent potential to become a new therapeutic strategy for IBD.

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The spread of capsule endoscopy has led to a focus on small intestinal injury induced by non-steroidal antiinflammatory drugs (NSAIDs). However, it has been proposed that proton pump inhibitors (PPI), a strong anti-secretary agent, have anti-inflammatory action beyond acid suppression. Therefore, we evaluated the biological effects of lansoprazole, a PPI used in the clinical area, in the setting of experimental rat non-steroidal anti-inflammatory drug-induced enteritis. The animals were given indomethacin subcutaneously and the intestinal mucosa was examined 24 h later. Lansoprazole was given subcutaneously just after following indomethacin injection. Single administration of indomethacin at 10 mg/kg provoked severe hemorrhagic lesions in the small intestine, mostly the jejunum and ileum. The levels of thiobarbituric acid-reactive substances (TBARS), the myeloperoxidase (MPO) activity and the content of cytokine-induced neutrophil chemoattractant-1 (CINC-1) in the intestinal mucosa significantly increased in indomethacin-treated groups compared with the sham-operated groups. The development of intestinal lesions in response to indomethacin was dose-dependently prevented by lansoprazole at a dose of 5 mg/kg together with significant suppression of the increased level of TBARS, MPO activities and CINC-1 in the small bowel. Furthermore, the increased CINC-1 mRNA expression after administration of indomethacin was also inhibited by treatment with lansoprazole. These results suggest that lansoprazole administered exogenously prevented the small intestine against indomethacin-induced damage, the action being dependent on its anti-inflammatory and anti-oxidative responses. This evidence supports the theory that PPI have an expanding role beyond acid suppression.

These findings suggest that visceral hypersensitivity in NERD patients is involved in neurogenic inflammation showing the increase in both substance P release and NK1R expression, which may be associated with the activation of TRPV1 and PAR2.