中国人兽共患病学报2017，Vol.33Issue(12)：1071-1076,6.DOI:10.3969/j.issn.1002-2694.2017.12.004
幽门螺杆菌Tipα蛋白激活NLRP3炎性小体诱导THP-1细胞分泌IL-1β和IL-18
Helicobacter pylori Tipα protein induces IL-1β and IL-18 production in THP-1-drived macrophages through activation of NLRP3 inflammasome
摘要
Abstract
We preliminarily investigated the role of NLRP3 inflammasome in Helicobacter pylori (H.pylori) Tipa-induced pro-inflammatory cytokines secretion in PMA-differentiated human acute monocytic leukemia cell line THP-1.PMA-differentiated THP-1 cells were treated with pure recombinant Tips protein.The secretion levels of TNF-α,IL-1β and IL-18 in supernatant of culture medium were detected by ELISA.Then we blocked MyD88/NF-κB and NLRP3/Caspase-1 pathways by PDTC or the general ROS scavenger,NAC,respectively,and determined the secretion levels of proinflammatory cytokines and the expression levels of NLRP3 and Caspase-1.The results showed that Tips protein can significantly induced the secretion of TNF-α,IL-1β and IL-18 in THP-1 cells in a time and dose-dependent manner.Levels of TNF-α,IL-1β and IL-18 approached their peaks at 6 h post-treatment by 40 μg/mL of Tipα protein (P＜0.05).Moreover,the blockade of NF-κB signaling pathway by PDTC can inhibit the secretion of proinflammatory cytokines and the expression of NLRP3 and Caspase-1.When THP-1 cells were pre-treated with ROS scavenger NAC,the Tipα-induced increased IL-1β and IL-18 secretion was obviously eliminated (P＜0.05),while TNF-α level had no significant difference,and the expression levels of Caspase-1 and NLRP3 also have a significant decrease.Our results demonstrated that Tipα can promote THP-1-drived macrophages to secrete proinflammatory cytokines TNF-α,IL-1β and IL-18,and the NLRP3/Caspase-1 pathway may be involved in the Tipα protein-induced IL-1β and IL-18 secretion.关键词
幽门螺杆菌/Tipα/NLRP3炎性小体/IL-1β/IL-18Key words
Helicobacter pylori/Tipα/NLRP3 inflammasome/IL-1β/IL-18分类
医药卫生引用本文复制引用
肖玲巧,张艳,王超,谢成元,刘硕,陈国栋,李杰,余敏君,赵兰华,韩亮..幽门螺杆菌Tipα蛋白激活NLRP3炎性小体诱导THP-1细胞分泌IL-1β和IL-18[J].中国人兽共患病学报,2017,33(12):1071-1076,6.基金项目
湖南省高校创新平台开放基金项目(No.16K078) （No.16K078）
湖南省科教联合基金项目(No.2017JJ5049) （No.2017JJ5049）
“特殊病原体防控”湖南省科技厅重点实验室资助项目[No.湘科计字(2014)5号]和湖南省分子靶标新药研究协同创新中心资助项目[湘教通(2014)405号、(2015)351号]联合资助 Supported by the Research Project of Hunan Provincial Education Department (No.16K078),the Joint Funds for Science and Education of Hunan Provincial Natural Science Foundation (No.2017JJ5049),the Hunan Provincial Key Laboratory for Special Pathogen Prevention and Control Foundation (No.2014-5),and the Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study (Nos.2014-405,2015-351) （2014）
