1,25-Dihydroxyvitamin D3 inhibits the cytokine-induced secretion of MCP-1 and reduces monocyte recruitment by human preadipocytes

BACKGROUND: Adipose tissue expansion during obesity is associated with a state of low-grade inflammation and an increase in macrophage infiltration, which predisposes to insulin resistance and vascular malfunction. Growing evidence suggests that vitamin D-3 has immunoregulatory effects and adipose tissue could be a target for vitamin D-3 action. Preadipocytes, one of the major cell types in adipose tissue, are actively involved in inflammatory processes. OBJECTIVES: This study investigated whether the active form of vitamin D-3 (1,25(OH)(2)D-3) affects the production of proinflammatory chemokines/cytokines and the monocyte recruitment by human preadipocytes. METHODS/RESULTS: The secretion levels of monocyte chemoattractant proteint-1 (MCP-1), IL-8 and IL-6 were significantly higher in preadipocytes than in differentiated adipocytes, suggesting that preadipocytes could be a major source of proinflammatory mediators. Cytokine profile analysis revealed that 1,25(OH)(2)D-3 (10 nM) markedly reduced the release of MCP-1, IL-6 and IL-8 by preadipocytes. The involvement of NFkB signalling was shown by the upregulation of I kappa B alpha protein abundance by 1,25(OH) 2D(3) in preadipocytes. In addition, 1,25(OH)(2)D-3 was able to decrease the migration of THP-1 monocytes. Treatment with proinflammatory stimuli, including macrophage-conditioned (MC) medium, TNF alpha and IL-1 beta, led to a marked increase in protein release of MCP-1 and IL-6 by preadipocytes. Pretreatment with 1,25(OH)(2)D-3 (10 nM and 100 nM) significantly decreased the stimulatory effects of MC medium, TNF alpha and IL-1 beta on MCP-1 expression and protein release, although the effect on stimulated release of IL-6 was less potent. CONCLUSIONS: These results demonstrate that 1,25(OH)(2)D-3 decreases the production of MCP-1 and other proinflammatory mediators by preadipocytes and reduces monocyte migration. Thus, vitamin D-3 may protect against adipose tissue inflammation by disrupting the deleterious cycle of macrophage recruitment. International Journal of Obesity (2013) 37, 357-364; doi:10.1038/ijo.2012.53; published online 17 April 2012