Bone marrow mesenchymal stem cell-induced autophagy ameliorates TNBS-induced experimental colitis by downregulating the NLRP3 inflammasome  

作　　者：JINJIN FU XIAOYUE FENG JUAN WEI XIANG GENG YU GONG FENGDONG LI SHAOHUA ZHUANG JIN HUANG FANGYU WANG 

机构地区：[1]Department of Gastroenterology,The Affiliated Changzhou No.2 People’s Hospital,Nanjing Medical University,Changzhou,China [2]Department of Gastroenterology,Jinling Hospital,Nanjing Medical University,Nanjing,China

出　　处：《BIOCELL》2023年第12期2627-2639,共13页生物细胞（英文）

摘　　要：This study aimed to elucidate the potential mechanisms through which bone marrow-derived mesenchymal stem cells(BM-MSCs)may be effective in alleviating experimental colitis induced by treatment with 2,4,6-trinitrobenzene-sulfonate acid(TNBS),specifically through autophagy modulation.Methods:BM-MSCs were collected from BALB/c mice for subsequent experiments.The study employed cell counting kits(CCK-8)to investigate the impact of the MSC-conditioned medium(M medium)on the proliferation of RAW264.7 macrophages.The GFP-mRFP-LC3 adenovirus was transfected into RAW264.7 to detect autophagic flux.The gene expression of cytokines was assessed through quantitative reverse transcription polymerase chain reaction(qRT-PCR).Western blot analysis was employed to determine the presence of a binding interaction between NOD-like receptor protein 3(NLRP3)and autophagy.Furthermore,a colitis mouse model was established by TNBS induction.Clinical disease activity score was assessed regularly,and histological and morphometric analyses were performed on colonic tissues.Inflammatory serum cytokines were identified using an enzyme-linked immunosorbent assay.Results:BM-MSCs significantly promoted the proliferation of RAW264.7.In vitro lipopolysaccharide(LPS)-stimulated RAW264.7 cells,treated with BM-MSCs,triggered autophagy and inhibited cytokine mRNA expression.Additionally,in LPS-induced RAW264.7,BM-MSCs enhanced the Beclin1 protein expression and the microtubule-associated protein 1 light chain 3(LC3)-II to LC3-I ratio while suppressing the protein levels of NLRP3 and apoptosis-associated speck-like protein(ASC).Nevertheless,3-methyladenine(3-MA),an inhibitor of autophagy,prevented the impact of BM-MSCs by reducing the levels of NLRP3 and ASC proteins,suggesting that autophagy triggered the inhibition of the NLRP3 inflammasome.In comparison to the mice in the TNBS group,the mice in the TNBS+MSC group displayed a more acute form of colitis,and the IL1βand IL18 cytokines in their serum were lowered as well.In the meantime,3-MA raised IL

关 键 词：RAW264.7 3-Methyladenine(3-MA) IL1β IL18 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]