P2X7 receptor inhibitor suppressed extracellular ATP/LPS-primed human hepatic stellate cells activation via downregulating NLRP3 inflammasome

作     者：ShuangJIANG QuanJIN Yan-lingWU You-liYAO Ji-xingNAN Li-huaLIAN 

作者机构：Key Laboratory for Natural Resource of Changbai Mountain &Functional Molecules Ministry of Education College of Pharmacy Yanbian University Yanji 133022 China 

出 版 物：《中国药理学与毒理学杂志》 (Chinese Journal of Pharmacology and Toxicology)

年 卷 期：2015年第29卷第S1期

页      面：67-68页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学] 

基　　金：The project supported by National Natural Science Foundation of China(81260664 81160538) 

主　　题：liver fibrosis hepatic stellate cells P2X7receptor 

摘      要：OBJECTIVE To investigate the effect of P2X7receptor(P2X7r)inhibition,using a specific inhibitor(A438079)to prevent the development of liver fibrosis on human hepatic stellate cells,*** The supernatant from lipopolysaccharide(LPS)-stimulated RAW264.7 mouse macrophages was supplemented to LX-2 cells for 24 ***-2cells were primed with LPS for 4h and subsequently stimulated for 30 min with 3mmol·L-1 of adenosine 5′-triphosphate(ATP).A438079(10μmol·L-1)was supplemented to LX-2 cells 10 min prior to *** Directly treated with LPS on LX-2 cells,mRNA expressions of IL-1β,IL-18 and IL-6 were increased,as well as P2X7 *** caspase-1,ASC and NLRP3 mRNA expressions were increased with LPS *** stimulation also increasedα-SMA and collagenⅠ mRNA *** treatment of LX-2cells with mediums from LPS-primed RAW264.7mouse macrophages exhibited greater increase of mRNA expressions of above genes than those in LX-2directly treated with *** of directly or indirectly LPS-stimulated LX-2 cells with A438079 both suppressed IL-1βmRNA *** addition treatment of LPS-primed LX-2 cells with 3mmol·L-1 ATP induced the significant increase of IL-1β,IL-6,caspase-1,pannexin-1,α-SMA and collagenⅠ mRNA expression,the increasing ofα-SMA protein expression and cleavage of IL-1β.These events were significantly suppressed by pretreatment with P2X7 rantagonist A438079.P2X7 rblockade also significantly reduced the protein expression ofα-*** Our results suggest that the involvement of the P2X7r-NLRP3 inflammasome pathway in the secretion of IL-1βfrom extracellular ATP/LPS-stimulated human hepatic stellate *** study demonstrated that repression of the P2X7 rrepresents a novel potential therapeutic approach to control liver fibrosis.