文献类型：期刊文献

英文题名：Mesenchymal Stromal Cells Directly Promote Inflammation by Canonical NLRP3 and Non-canonical Caspase-11 Inflammasomes

作者：Chen, Yaozhen[1,2];Qin, Xiangyang[3];An, Qunxing[1];Yi, Jing[1];Feng, Fan[4];Yin, Dandan[5];An, Ning[1];Liu, Zheng[6];Weng, Lihong[7];Chen, Shouwen[8];Hu, Xingbin[1];Yin, Wen[1,2]

机构：[1]Fourth Mil Med Univ, Xijing Hosp, Dept Transfus Med, Xian 710032, Shaanxi, Peoples R China;[2]Fourth Mil Med Univ, Sch Basic Med, Dept Microbiol, Xian 710032, Shaanxi, Peoples R China;[3]Fourth Mil Med Univ, Sch Pharm, Dept Chem, Xian 710032, Shaanxi, Peoples R China;[4]Fourth Mil Med Univ, Xijing Hosp Digest Dis, Div Digest Surg, Xian 710032, Shaanxi, Peoples R China;[5]Fourth Mil Med Univ, Tangdu Hosp, Dept Hematol, Xian 710032, Shaanxi, Peoples R China;[6]Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA;[7]City Hope Natl Med Ctr, Dept Hematol & Hematopoiet Cell Transplantat, Duarte, CA 91010 USA;[8]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China

年份：2018

卷号：32

起止页码：31

外文期刊名：EBIOMEDICINE

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000436312000008)】；

基金：This work was supported by Key Science and Technology Programs of Shaanxi Province of China NO . S2018-YF-YBSF-0556 (X.H.) and 2015SF195(X.Q.), and National Natural Science Foundation of China NO. 81202421(X.Q.). The information contained in the manuscript is the sole responsibility of the authors, no funding source was involved in the collection, analysis, or interpretation of the data nor the manuscript preparation.

语种：英文

外文关键词：Mesenchymal stromal cells; Inflammasome; NLRP3; Caspase-11; Pyroptosis

摘要：Mesenchymal stromal cells (MSCs) based therapy is a promising approach to treat inflammatory disorders. However, therapeutic effect is not always achieved. Thus the mechanism involved in inflammation requires further elucidation. To explore the mechanisms by which MSCs respond to inflammatory stimuli, we investigated whether MSCs employed inflammasomes to participate in inflammation. Using in vitro and in vivo models, we found that canonical NLRP3 and non-canonical caspase-11 inflammasomes were activated in bone-associated MSCs (BA-MSCs) to promote the inflammatory response. The NLRP3 inflammasome was activated to mainly elicit IL-1 beta/18 release, whereas the caspase-11 inflammasome managed pyroptosis. Furthermore, we sought a small molecule component (66PR) to inhibit the activation of inflammasomes in BA-MSCs, which consequently improved their survival and therapeutic potential in inflammation bowel diseases. These current findings indicated that MSCs themselves could directly promote the inflammatory response by an inflammasomedependent pathway. Our observations suggested that inhibition of the proinflammatory property may improve MSCs utilization in inflammatory disorders. (C) 2018 The Authors. Published by Elsevier B.V.