| 以下仅列出文章摘要、提纲简介，如需获取全文阅读权限，或原创定制、长期合作，请随时联系。 微信QQ:312050216 |
 |
 |
| Growth differentiation factor 11 ameliorates murine experimental colitis by inhibiting NLRP3 inflammasome activation Abstract Background and Aim: Because drugs for ulcerative colitis (UC) have obvious limitations, such as lacking stable, long-term clinical effects and with adverse incident, exploring alternative therapies for UC has become a hot point in research. The NLRP3 inflammasome is closely associated with intestinal inflammation due to its ability to increase IL-1β secretion. Recently, studies have shown that Growth differentiation factor 11(GDF11) has anti-aging and anti-inflammatory effects in aged mice. Our aim is to determine whether GDF11 has the effect in attenuating experimental colitis in mice. Methods: Mice with dextran sulfate sodium (DSS)-induced UC were treated with GDF11-Fc, hIgG or Enbrel by intraperitoneal injection. The body weight, severity of disease activity index (DAI), the lengthen and histological change in colon were determined. The level of IL-1β secretion and NLRP3 inflammasome activation in colon were detected. RAW264.7 cells were used to further investigate the possible mechanism of inhibiting NLRP3 inflammasome by GDF11. Results: We found that GDF11 could attenuate loss of body weight, the severity of DAI, shortening of the colon, and histological changes in the colon. GDF11 treatment remarkably suppressed IL-1β secretion in the colon samples and RAW264.7 cells, as well as NLRP3 inflammasome activation, including the expression of NLRP3 and cleaved caspase1. Furthermore, we found that GDF11 treatment inhibited NLRP3 inflammasome activation by downregulating the NF-κB p65 pathway and reactive oxygen species production via the typical Smad2/3 pathway. Conclusions: Our results demonstrate that GDF11 inhibits NLRP3 inflammasome activation, providing some basis for its potential use in the treatment of UC. Keywords: GDF11, experimental colitis, NLRP3 inflammasome |
