The Study Of OxLDL Induced Functional Changes Of Human Macrophage And Related Regulation Mechanism

Objective:By studying the oxLDL induced functional changes of human macrophage including inflammasome priming,activation,pyroptosis,lipid-phagocytosis and efferocytosis,to investigate the role and mechanisms of macrophage functions in the development of atherosclerosisMethods:THP1 cells were treated with oxLDL,followed by testing functional changes including inflammasome priming,activation,pyroptosis,lipid-phagocytosis and efferocytosis.THP1 cells were pretreated with PTL which can inhibit nuclear factor-KB(NF-κB)pathway,followed by testing oxLDL induced functional changes to clarify interaction between NF-κB and oxLDL-treated macrophages.Further,THP1 cells were pretreated with clinical effective drugs for ischemic stroke patients Butylphthalide(NBP)or Ginkgo Diterpene Lactone(GDL),followed by testing oxLDL induced functional changes to clarify the potential mechanisms of these drugsResults:1.Compared with the control group,the expression of the inflammasome priming marker pro-IL1β in THP1 cells significantly increased in oxLDL group、PTL group、PTL-oxLDL group.oxLDL induced the inflammasome priming by upregulating the NF-κB pathway while PTL induced the inflammasome priming by some other pathways instead of NF-κB pathway2.Compared with the control group,no alteration was observed in the expression of the inflammasome activation markers NLRP3,ASC,caspasel(p45,p20),pro-IL1β in THP1 cells in oxLDL group、PTL group、PTL-oxLDL group3.Compared with the control group,there was no obvious pyroptosis in THP1 cells in oxLDL group、PTL group、PTL-oxLDL group.4.Compared with the control group,the amount of lipid phagocytized by THP1 cells significantly increased in oxLDL group.oxLDL induced the lipid-phagocytosis by upregulating the NF-κB pathway.Pretreatment with NBP enhanced oxLDL induced lipid-phagocytosis while GDL had no effect on oxLDL induced lipid-phagocytosis.5.Compared with the control group,the ability of THP1 cells to ’bury dead cells’significantly increased in oxLDL group.oxLDL induced the efferocytosis by upregulating the NF-κB pathway.Pretreatment with NBP enhanced oxLDL induced efferocytosis while GDL had no effect on oxLDL induced efferocytosis.Conclusion:1.oxLDL can induce inflammasome priming,lipid-phagocytosis and efferocytosis of THP1 cells.2.NF-κB pathway regulates the oxLDL induced functional changes of THP1 cells including inflammasome priming,lipid-phagocytosis and efferocytosis.3.NBP enhances the oxLDL induced functional changes of THP1 cells including lipid-phagocytosis and efferocytosis while GDL had no effect on these functional changes.