Sirtuin 7 Inhibitor Attenuates Colonic Mucosal Immune Activation in Mice-Potential Therapeutic Target in Inflammatory Bowel Disease

Abstract

Accumulating evidence has shown that sirtuin 7 (SIRT7), a mediator of various cellular activities, plays an important role in the pathogenesis of various immune-mediated inflammatory disorders. However, information remains limited regarding the role of SIRT7 in intestinal inflammation. We used a murine colitis model to investigate the role of SIRT7 in intestinal immunity and whether SIRT7 inhibitors could attenuate the intestinal inflammatory response. Mice were divided into three groups: control, colitis-induced, and SIRT7-inhibitor-treated. A colitis mouse model was established by intraperitoneal injection and nasal challenge with ovalbumin, as in our previous study. Quantitative analyses of inflammatory cytokines and SIRT7 levels in the colonic mucosa were performed to compare the changes in inflammatory responses between the three groups. The colitis group showed increased levels of inflammatory cytokines and SIRT7 in the colonic mucosa. The inflammatory reaction was suppressed in colitis-induced mice administered the SIRT7 inhibitor. The qRT-PCR results showed normalization of inflammatory cytokines in the SIRT7 inhibitor-treated group. Histologic study revealed a decrease in the extent of inflammation after SIRT7 treatment. We also observed that the degree of clinical inflammation was improved in SIRT7-treated mice. Our study demonstrated that SIRT7 inhibition attenuated the inflammatory response in the colon of mice, suggesting a possible role for SIRT7 in the pathogenesis of immune-mediated intestinal inflammation.