关键词: IL-1, 泡沫细胞, 脂酰CoA胆固醇酯酰转移酶-1, 蛋白激酶C, 丝裂原激活蛋白激酶

Abstract: Abstract Objective Our current investigation attempts to study whether interleukin-1 (IL-1) increases foam cells acyl-CoA cholesterol ester acyltransferase-1 (ACAT-1) expression and activity by protein kinase C (PKC)/mitogen-activated protein kinase (MAPK) signaling pathway. Methods The mononuclear cells (THP-1) were co-cultured with phorbol myristate acetate (PMA) and induced into differentiation to macrophages. The macrophages were cultured with oxidized low density lipoprotein (Ox-LDL) and induced into differentiation to the foam cells. Oil red O staining was employed to examine cytoplasm lipid deposition. PKC and MAPK activity was detected in three different groups (the foam cells group, the foam cells plus IL-1 group, the foam cells plus IL-1/IL-1 monoclonal antibody group). PKC and MAPK inhibitors were separately added to the three different groups. Western blot assay and liquid phase scintillation counting were employed to examine the expression of ACAT-1 protein and ACAT-1 activity in different groups, respectively. Results THP-1 cells presented a suspension growth pattern, and showed significant changes including the adhensive growth, ovalisation shape after cultured in RPMI l640 media containing 200nM PMA for 48h. Some red stained substance could be found in the cytolymph after co-cultured with 100mg/L Ox-LDL for 24h. The PKC and MAPK activities in the the foam cells plus IL-1 group are higher than those in the foam cells group (P<0.05). The expression and activity of ACAT-1 in the the foam cells plus IL-1 group are higher than those in the foam cells group (P<0.05). After added PKC and MAPK inhibitors, the up-regulation effects of IL-1 on the expression and activity of ACAT-1 were remarkably decreased (P<0.05). Conclusions PKC/MAPK signaling pathway could be involved in the IL-1 up-regulation effects on the ACAT-1 expression and activity in the the foam cells.

Key words: IL-1, foam cells, Acyl-CoA:Cholesterol Acyltransferase-1, protein kinase C, Mitogen-activated protein kinase