Acute pancreatitis (AP) is a severe inflammatory disease. Caerulin induces significant pro-inflammatory responses in macrophages, causing serve damage to pancreatic acinar cells. The potential role of Rab GTPase 21 (Rab21) in this process was tested in this study. In murine bone marrow-derived macrophages (BMDMs), caerulin induced Rab21-TRAF3-MKK3 complex association. Rab21 silencing (by targeted shRNAs) or knockout (by CRISPR/Cas9 method) largely inhibited caerulin-induced MKK3-TRAF3 association, downstream MKK3-p38 activation and production of several pro-inflammatory cytokines (IL-1 beta, TNF-alpha and IL-17). Conversely, ectopic Rab21 overexpression in BMDMs potentiated caerulin-induced MKK3-TRAF3 association and pro-inflammatory cytokines production. The cytotoxicity of caerulin-activated BMDMs to co-cultured pancreatic acinar cells was alleviated by Rab21 knockdown or knockout, but exacerbated with Rab21 overexpression. In vivo, administration of Rab21 shRNA lentivirus significantly attenuated pancreatic and systemic inflammations in caerulin-injected AP mice. Collectively, our results suggest that Rab21 mediates caerulin-induced MKK3-p38 activation and pro-inflammatory responses. (C) 2019 Elsevier Inc. All rights reserved.
基金：
Foundation of Changning District Commission of Health and Family Planning, Shanghai [20154Y002]; Shanghai Changning Science and Technology Committee [CNKW2015Y03]
第一作者机构：[1]Shanghai Jiao Tong Univ, Sch Med, Shanghai Tongren Hosp, Dept Gastroenterol, 1111 Xianxia St, Shanghai 200336, Peoples R China
通讯作者：
通讯机构：[1]Shanghai Jiao Tong Univ, Sch Med, Shanghai Tongren Hosp, Dept Gastroenterol, 1111 Xianxia St, Shanghai 200336, Peoples R China[*1]Department of Gastroenterology, Shanghai Tongren Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, The 1111 Xianxia Street, Shanghai, 200336, China.
推荐引用方式(GB/T 7714)：
Wang Na,Meng Wenying,Jia Rongrong,et al.Rab GTPase 21 mediates caerulin-induced TRAF3-MKK3-p38 activation and acute pancreatitis response[J].BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS.2019,518(1):50-58.doi:10.1016/j.bbrc.2019.08.007.
APA：
Wang, Na,Meng, Wenying,Jia, Rongrong&Xiang, Shihao.(2019).Rab GTPase 21 mediates caerulin-induced TRAF3-MKK3-p38 activation and acute pancreatitis response.BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,518,(1)
MLA：
Wang, Na,et al."Rab GTPase 21 mediates caerulin-induced TRAF3-MKK3-p38 activation and acute pancreatitis response".BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 518..1(2019):50-58
