Tomohisa Takagi

Anti-tryptase treatment using nafamostat mesilate has a therapeutic effect on experimental colitis

Objective. Mast cell tryptase has been proposed to be involved in the pathogenesis of human inflammatory bowel disease (IBD). Recently, it was reported that a low dose of nafamostat mesilate (NM), a serine protease inhibitor that is widely used to treat disseminated intravascular coagulation (DIC) and acute pancreatitis, can selectively inhibit human tryptase activity. The aim of this study was to investigate the anti-inflammatory effects of NM on experimental colitis in rats. Material andmethods. Colitis was induced in male Wistar rats using an enema of trinitrobenzene sulfonic acid (TNBS) dissolved in 50% ethanol. NM or 5-aminosalicylic acid (5-ASA), foundation therapy for mild-to-moderate IBD, was administered via the anus once a day on each of the 6 days after administration of TNBS. Colonic inflammation was assessed 1 week after TNBS administration. Results. Intracolonic administration of TNBS resulted in the infiltration of numerous tryptase-positive cells in the colonic mucosa. The colonic mucosal injury induced by TNBS was significantly decreased by treatment with NM or 5-ASA. The increases in thiobarbituric acid-reactive substances (TBA-RS), myeloperoxidase (MPO) activity, tumor necrosis factor (TNF)-α and cytokine-induced neutrophil chemoattractants-1 (CINC-1) in the colonic mucosa were inhibited in the NM group and the 5-ASA group, without significant differences between them. Conclusions. 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.

Review article: anti-tryptase therapy in inflammatory bowel disease: REVIEW: ANTI-TRYPTASE THERAPY IN IBD

A number of studies have shown that activated mast cells are involved in the pathogenesis of inflammatory and allergic diseases.

Increased intestinal luminal carbon monoxide gas in patients with ulcerative colitis: CARBON MONOXIDE IN ULCERATIVE COLITIS

Recent studies in models of inflammatory bowel disease have demonstrated that heme oxygenase‐1 (HO‐1) induction, or its by‐products in this process such as carbon monoxide (CO), plays an important role in the intestinal inflammation. However, the distribution of HO‐1 in intestinal mucosa and the concentration of intestinal luminal CO in humans have not yet been investigated.

Gene expression clusters of a lipopolysaccharide-stimulated pathway in peripheral blood monocytes of Japanese patients with Crohn's disease: GENE EXPRESSION IN CROHN'S DISEASE

Recent reports support the notion that patients with Crohns disease have a dysregulated innate immune response to endogenous flora.