1,25-dihydroxyvitamin D(3) 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 AND RESULTS: The secretion levels of 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 NFκB signaling was shown by the upregulation of IκBα protein abundance by 1,25(OH)(2)D(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, TNFα and IL-1β, 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, TNFα and IL-1β 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.