P45 Endogenous hydrogen sulfide suppresses intestinal inflammation through the regulation of macrophage polarization

Introduction Accumulating evidence shows the role of endogenous hydrogen sulfide (H 2 S) in various disease, whereas its role of H 2 S in intestinal inflammation. In addition, recent reports showed that H 2 S modulates NF-kB signaling in macrophages, suggesting that H 2 S could affect macrophage function. In this study, we studied the role of endogenous H 2 S in a dextran sodium sulfate (DSS)-induced colitis model, particularly in relation to macrophage function. Methods Mice were treated with 8% DSS to induce colitis. DL-propargylglycine (PAG), an irreversible CSE (cystathionine gamma-lyase) inhibitor, and sodium sulfide (Na 2 S), an H 2 S donor, were administered intraperitoneally. The respective degrees of mucosal injury were evaluated macroscopically, histologically, and biochemistry. The effect of endogenous H 2 S on macrophage function was evaluated using bone-marrow derived macrophages (BMDMs). Results CSE and CBS (cystathionine beta-synthase) expressions in the colonic mucosa were increased in DSS-treated mice. PAG enhanced DSS-induced colonic damage and myeloperoxidase activity. Meanwhile, Na 2 S counteracted these effects of PAG. Furthermore, PAG-treated BMDMs manifested pro-inflammatory (M1), but not anti-inflammatory (M2) macrophages markers. Conclusion Our results demonstrated that endogenous H 2 S inhibited the development of intestinal inflammation through the regulation of macrophage function. In conclusion, H 2 S may be a novel therapeutic molecule in intestinal inflammation.