Vitamin D inhibits palmitate-induced macrophage pro-inflammatory cytokine production by targeting the MAPK pathway

Vitamin D insufficiency is associated with chronic inflammatory diseases. However, the mechanism by which vitamin D reduces obesity-related inflammation remains poorly understood. In this study, we investigated the inhibitory effects of vitamin D on palmitate-induced inflammatory response in macrophages and explored the potential mechanisms of vitamin D action. The effect of vitamin D on the expression of inflammatory factors induced by palmitate, a saturated fatty acid, was investigated using human THP-1 macrophages and murine RAW 264.7 cells. To elucidate the mechanism by which vitamin D affects palmitate-induced inflammatory cytokine production, we investigated the activity of stress kinase-related proteins. Palmitate significantly increased TNF-α and IL-6 expression and secretion in THP-1 and RAW 264.7 macrophages. Treatment with the active form of vitamin D inhibited palmitate-induced TNF-α and IL-6 production in macrophages. Furthermore, vitamin D significantly reduced palmitate-stimulated activation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase 1/2 (ERK1/2). The mitogen-activated protein kinase signaling pathway partly accounts for the induction of pro-inflammatory cytokines by palmitate. Our data suggest that the attenuation of palmitate-induced TNF-α and IL-6 gene expression and protein secretion by vitamin D are associated with reduced activation of JNK and ERK1/2.