Vitamin D inhibits the Staphylococcal enterotoxin B-induced expression of tumor necrosis factor in microglial cells.

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Microglial cells play a crucial role in inflammatory responses in neural tissue. Vitamin D (VitD3) deficiency is associated with the pathogenesis of inflammation. Staphylococcal enterotoxin B (SEB) is a superantigen and can initiate inflammation. This study tests a hypothesis that VitD3 deficiency upregulates the expression of tumor necrosis factor (TNF) in microglial cells. Microglial cells were isolated from the mouse brain. The microglial cells were cultured in the presence or absence of VitD3 or/and SEB. The expression of TNF in the microglial cells was assessed by RT-qPCR and Western blotting. We observed that SEB increased the expression of TNF in microglial cells. The presence of calcitriol (an active form of VitD3) inhibited the SEB-induced TNF production by microglial cells in a dose-dependent manner. Exposure to SEB increased the binding of vitamin D receptor (VDR) to the TNF promoter, which was inhibited by the presence of calcitriol with the mechanism being the formation of a complex of VDR and LITAF (a transcription factor of TNF) in microglial cells; the complex prevented the binding of LITAF to the promoter of the TNF gene. Exposure to calcitriol also increased the expression of IL-10 in microglial cells; the inhibition of SEB-induced TNF expression was partially due to the IL-10 induced by calcitriol (Heine G, Niesner U, Chang HD, teinmeyer A, Zügel U, Zuberbier T, et al. 1,25-dihydroxyvitamin D(3) promotes IL-10 production in human B cells. Eur J Immunol. 2008;38(8):2210-8). Hormonal vitamin D [calcitriol] can inhibit the SEB-induced TNF expression in microglial cells.