Effect of Vitamin D3 on Monocyte Chemoattractant Protein 1 Production in Monocytes and Macrophages.

ABSTRACT

BACKGROUND: Chemokine is important in the initiation and progression of atherosclerosis, the clinically manifest stages of atherosclerosis and acute coronary syndrome. Vitamin D deficiency has been reportedly linked with hypertension and myocardial infarction, as well as other cardiovascular-related diseases, such as congestive heart failure, peripheral vascular disease and atherosclerosis. Monocyte chemoattractant protein 1 (MCP-1) mediates atherosclerosis and other cardiovascular diseases. However, there have been few studies conducted about the role of 1α,25-(OH)2D3 on MCP-1 expression in human monocytes. METHODS: We investigated the effects of vitamin A, C and 1α,25-(OH)2D3, three common vitamins, to better ascertain MCP-1 expression in human monocyte and also the associated intracellular mechanism. Human monocyte cell line (THP-1 cell) and THP-1 cell-induced macrophage were treated with varying doses of vitamin A, C and 1α,25-(OH)2D3 for 2 hours before LPS stimulation. Supernatants were harvested to measure MCP-1 levels by the enzyme-linked immunosorbent assay (ELISA). The intracellular mechanism about the effects of vitamin A, C and 1α,25-(OH)2D3 on the expression of MCP-1 expression in human monocytes was assessed by western blot. RESULTS: We found that Lipopolysaccharides (LPS)-induced MCP-1 production was suppressed by 1α,25-(OH)2D3 in THP-1 cells and THP-1-induced macrophage. Only high concentration of vitamin A and C could reduce LPS-induced MCP-1 production in THP-1-induced macrophage, but not in THP-1 cells. LPS-induced p38 expression in THP-1 cells was suppressed by 1α,25-(OH)2D3. A selective p38 pathway inhibitor SB203580 could also suppress LPS-induced MCP-1 production. However, vitamin D receptor blocking antibody could reverse the suppressive effect of 1α,25-(OH)2D3 on MCP-1 expression. CONCLUSIONS: These data demonstrate that 1α,25-(OH)2D3 is effective in down-regulating LPS-induced MCP-1. The suppressive effect on MCP-1 may, at least in part, involve the vitamin D receptor and down-regulation of LPS - induced p38 expression. KEY WORDS Chemokine; Monocyte chemoattractant protein 1 (MCP-1); Monocyte; p38; Vitamin D.