Effects And Mechanisms Of Curcumin On THP-1 Cell-derived Macrophage Polarization

ObjectivesCurcumin, the active ingredient in curcuma rhizomes, has a wide range of therapeutic effects. However, its atheroprotective activity in human acute monocytic leukemia THP-1 cells remains unclear. We investigated the activity and molecular mechanism of action of curcumin in polarized macrophages. MethodsPhorbol myristate acetate(PMA)-treated THP-1 cells were differentiated to macrophages, which were further polarized to M1 cells by lipopolysaccharide(LPS; 1 ?g/ml) and interferon-?(IFN-?; 20 ng/ml) and treated with varying curcumin concentrations(0-30 ?mol/L). [3H]thymidine(3H-TdR) incorporation assays were utilized to measure curcumin-induced growth inhibition. The expression of tumor necrosis factor-?(TNF-?), interleukin(IL-6), and IL-12 were measured by quantitative real-time polymerase chain reaction(PCR) and enzyme-linked immunosorbent assay(ELISA). Macrophage polarization and its mechanism were evaluated by flow cytometry and western blot. Additionally, toll-like receptor 4(TLR4) small interfering RNA and mitogen-activated protein kinase(MAPK) inhibitors were used to further confirm the molecular mechanism of curcumin on macrophage polarization. ResultsCurcumin dose-dependently inhibited M1 macrophage polarization and the production of TNF-?, IL-6, and IL-12 compared with the control group. Curcumin also decreased TLR4 expression, which regulates M1 macrophage polarization. Furthermore, curcumin significantly inhibited the phosphorylation of ERK, JNK, p38, and nuclear factor(NF)-?B. In contrast, siTLR4 in combination with p-JNK, p-ERK, and p-p38 inhibition reduced the effect of curcumin on macrophage polarization. ConclusionsCurcumin can modulate macrophage polarization through TLR4-MAPK/NF-?B pathway inhibition, indicating that its effect on macrophage polarization is related to its anti-inflammatory and atheroprotective effects. Our data suggest that curcumin could be used as a therapeutic agent in atherosclerosis.