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 D3 has immunoregulatory effects and adipose tissue could be a target for vitamin D3 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 D3 (1,25(OH)2D3) 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)2D3 (10 nM) markedly reduced the release of MCP-1, IL-6 and IL-8 by preadipocytes. The involvement of NFκB signalling was shown by the upregulation of IκBα protein abundance by 1,25(OH)2D3 in preadipocytes. In addition, 1,25(OH)2D3 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)2D3 (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)2D3 decreases the production of MCP-1 and other proinflammatory mediators by preadipocytes and reduces monocyte migration. Thus, vitamin D3 may protect against adipose tissue inflammation by disrupting the deleterious cycle of macrophage recruitment.