IL-1 increases expression and activity of ACAT-1 in foam cells via protein kinase C/mitogen activated protein kinase pathway

Objective To investigate potential effect of interleukin-1(IL-1) of increasing Acyl-CoA;on cholesterol acyltransferase-1(ACAT-1) expression and activity in foam cells by protein kinase C(PKC)/mitogen-activated protein kinase(MAPK) signaling pathway.Methods Human monocytic leukemia cell line/(THP-1) was co-cultured with phorbol myristate acetate(PMA) and induced to differentiation into macrophages.The macrophages were cultured with oxidized low density lipoprotein(Ox-LDL) and induced to differentiate into foam cells.Oil red O staining was employed to examine cytoplasm lipid deposition.Activity of PKC was detected by Pep Tag assay for non-radioactive detection and MAPK activity was detected by Western blot in three different groups(the foam cells group,the foam cells IL-1 group,the foam cells IL-1/IL-1 monoclonal antibody group).PKC and MAPK inhibitors were separately added to the three different groups.Western blot and liquid phase scintillation counting were employed to examine the expression of ACAT-1 protein and ACAT-1 activity in different groups,respectively.ResultsTHP-1 cells presented a suspension growth pattern,and showed significant changes in adhensive growth and oval shape.The PKC and MAPK activities in the the foam cells IL-1 group were higher than those in the foam cells group(P0.05).The expression and activity of ACAT-1 in the the foam cells IL-1 group were higher than those in the foam cells group(P0.05).After added PKC and MAPK inhibitors,the up-regulation effects of IL-1 on the expression and activity of ACAT-1 were remarkably decreased(P0.05).Conclusion PKC/MAPK signaling pathway is involved in the IL-1 up-regulation effects on the ACAT-1 expression and activity in the the foam cells.