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,LX-2.METHODS The supernatant from lipopolysaccharide(LPS)-stimulated RAW264.7 mouse macrophages was supplemented to LX-2 cells for 24 h.LX-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 ATP.RESULTS Directly treated with LPS on LX-2 cells,mRNA expressions of IL-1β,IL-18 and IL-6 were increased,as well as P2X7 r.And caspase-1,ASC and NLRP3 mRNA expressions were increased with LPS stimulation.LPS stimulation also increasedα-SMA and collagenⅠ mRNA expressions.Interestingly 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 LPS.Pretreatment of directly or indirectly LPS-stimulated LX-2 cells with A438079 both suppressed IL-1βmRNA expression.In 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-SMA.CONCLUSION 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 cells.This study demonstrated that repression of the P2X7 rrepresents a novel potential therapeutic approach to control liver fibrosis. OBJECTIVE To investigate the effect of P2X7 receptor (P2X7r) inhibition, using a specific inhibitor (A438079) to prevent the development of liver fibrosis on human hepatic stellate cells, LX-2.METHODS The supernatant from lipopolysaccharide (LPS) -stimulated RAW 264.7 mouse macrophages were supplemented to LX-2 cells for 24 h.LX-2 cells were primed with LPS for 4 h and followed stimulated for 30 min with 3 mmol·L-1 of adenosine 5’-triphosphate (ATP). A438079 (10 μmol·L -1 ) were supplemented to LX-2 cells 10 min prior to ATP.RESULTS Directly treated with LPS on LX-2 cells, mRNA expressions of IL-1β, IL-18 and IL-6 were increased, as well as P2X7 r.And caspase -1, ASC and NLRP3 mRNA expressions were increased with LPS stimulation. LPS stimulation also increased α-SMA and collagen I mRNA expressions .restressed treatment of LX-2 cells with mediums from LPS-primed RAW264.7 mouse macrophages extracted greater increase of mRNA expressions of genes than those in LX-2 directly treated with LPS.Pretreatme NTP directly or indirectly in LPS-stimulated LX-2 cells with A438079 both suppressed IL-1β mRNA expression. In addition treatment of LPS-primed LX-2 cells with 3 mmol·L-1 ATP induced the significant increase of IL-1β, IL- 6, caspase-1, pannexin-1, α-SMA and collagenⅠ mRNA expression, the increasing of α-SMA protein expression and cleavage of IL-1β. Thesese events were significantly suppressed by pretreatment with P2X7 rantagonist A438079.P2X7 rblockade also significantly reduced the Protein expression of α-SMA. CONCLUSION 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 cells. This study represents that repression of the P2X7 rrepresents a novel potential therapeutic approach to control liver fibrosis