Effects of vitamin D on maturation and fatty acid metabolism in bone marrow-derived dendritic cells from atherosclerotic mice.

OBJECTIVE

Dendritic cells (DCs) play a pivotal role in the progression of atherosclerosis by modifying cell surface markers and cytokine secretion. While vitamin D is recognized for its ability to suppress the maturation of DCs, its effects on fatty acid metabolism in DCs remain unclear. This study investigated the effects of vitamin D on fatty acid metabolism and maturation in bone marrow-derived dendritic cells (BMDCs) from control (CON) and Ldlr-/- (ATH) mice.

MATERIALS AND

METHODS

Six-week-old male C57BL/6J mice were fed a control diet containing 1000 or 10,000 International Units (IU) of vitamin D3/kg diet (CON-vDC or CON-vDS), while Ldlr-/- mice were fed a Western diet containing 1000 or 10,000 IU of vitamin D3/kg diet (ATH-vDC or ATH-vDS) for 16 weeks. BMDCs were differentiated from bone marrow cells for 7 days and treated with 1α,25-Dihydroxyvitamin D3 (1,25(OH)2D3) (0 or 10 nM) during the culture period. On day 6, BMDCs were stimulated with lipopolysaccharide (LPS) for 24 h to induce maturation.

RESULTS

In vitro 1,25(OH)2D3 treatment reduced surface marker expression including major histocompatibility complex class II (MHC II), cluster of differentiation (CD)80, CD86, CD40, and interleukin (IL)-12p70 production. AMP-activated protein kinase (AMPK) expression was higher in the vitamin D supplemented group. Moreover, in vitro 1,25(OH)2D3 treatment downregulated expression of fatty acid synthesis-related genes (Srebp1c, Acaca, and Fasn) in immature BMDCs. Fatty acid oxidation-related gene expression (Cpt1α and Pparg) increased in the CON group but decreased in the ATH group with in vitro 1,25(OH)2D3 treatment.

CONCLUSION

These findings suggest that vitamin D may inhibit the mature BMDC phenotype by regulating fatty acid metabolism in BMDCs.