Sodium Absorption Stimulator Prostasin (PRSS8) Has an Anti-inflammatory Effect Via Downregulation of TLR4 Signaling in Inflammatory Bowel Disease

Overview

Journal J Gastroenterol

Specialty Gastroenterology

Date 2020 Jan 10

PMID 31916038

Citations 7

Authors

Yoshihiko Sugitani

Atsushi Nishida

Osamu Inatomi

Masashi Ohno

Takayuki Imai

Masahiro Kawahara

Kenichiro Kitamura

Akira Andoh

Affiliations

Soon will be listed here.

Abstract

Background: Prostasin (PRSS8) is a stimulator of epithelial sodium transport. In this study, we evaluated alteration of prostasin expression in the inflamed mucosa of patients with inflammatory bowel disease (IBD) and investigated the role of prostasin in the gut inflammation.

Methods: Prostasin expression was evaluated by immunohistochemical staining. Dextran sodium sulfate (DSS)-colitis was induced in mice lacking prostasin specifically in intestinal epithelial cells (PRSS8 mice).

Results: In colonic mucosa of healthy individuals, prostasin was strongly expressed at the apical surfaces of epithelial cells, and this was markedly decreased in active mucosa of both ulcerative colitis and Crohn's disease. DSS-colitis was exacerbated in PRSS8 mice compared to control PRSS8 mice. Toll-like receptor4 (TLR4) expression in colonic epithelial cells was stronger in DSS-treated PRSS8 mice than in DSS-treated PRSS8 mice. NF-κB activation in colonic epithelial cells was more pronounced in DSS-treated PRSS8 mice than in DSS-treated PRSS8 mice, and the mRNA expression of inflammatory cytokines was significantly higher in DSS-treated PRSS8 mice. Broad-spectrum antibiotic treatment completely suppressed the exacerbation of DSS-colitis in PRSS8 mice. The mRNA expression of tight junction proteins and mucosal permeability assessed using FITC-dextran were comparable between DSS-treated PRSS8 and DSS-treated PRSS8 mice.

Conclusion: Prostasin has an anti-inflammatory effect via downregulation of TLR4 expression in colonic epithelial cells. Reduced prostasin expression in IBD mucosa is linked to the deterioration of local anti-inflammatory activity and may contribute to the persistence of mucosal inflammation.

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