Objective To explore the role and possible mechanisms of bone marrow mesenchymal stem cell(BMSC)in the lipopolysaccharide(LPS)-induced inflammatory response involving alveolar macrophages through the inflammatory pathways.Methods ptges and ptges shRNA were transfected into BMSC by lentivirus,and stable ptges overexpression BMSC(BMSC-PGE2(+))and PTGEs silencing BMSC(BMSC-PGE2(-))were established.Macrophages were divided into control group,LPS group,LPS+BMSC group,LPS+BMSC-PGE2(+)group and LPS+BMSC-PGE2(-)group.The expression levels of nucleotide-bound oligomerized domain-like receptor 3(NLRP3),precursor cysteinyl aspartate specific proteinase 1(pro-caspase-1),caspase-1 and pro-IL-1β proteins were detected by Western blot.The mRNA expression levels of NLRP3 and caspase-1 were determined by RT-PCR.The expression levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),IL-10,IL-18 and prostaglandin E2(PGE2)in cell supernatant were detected by ELISA.Results The intervention of LPS significantly increased the expression of NLRP3,pro-caspase-1,caspase-1 and pro-IL-1β in macrophages.After co-culture with BMSC,the expression of each protein decreased significantly.After the overexpression of PGE2,the difference of protein expression further decreased.The expression of NLRP3 and caspase-1 mRNA in LPS group increased significantly,but decreased significantly after co-culture with BMSC.Overexpression of PGE2 could increase this difference,but there was no significant change in PGE2 silent group.The results of ELISA showed that the contents of TNF-α,IL-1 β and IL-18 in cell supernatant were the highest in LPS group.Adding BMSC and overexpressing PGE2 could decrease the related inflammatory factors.The levels of IL-10 and PGE2 in LPS group were higher than those in control group,and further increased in LPS+BMSC group and LPS+BMSC-PGE2(+)group with significant differences.Conclusions When inflammation is induced by LPS,BMSC can significantly mitigate the inflammatory response within macrophages.This process is likely mediated through the overexpression of PGE2,which inhibits the NLRP3-mediated pyroptosis pathway.
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