25(OH)D 3 and 1.25(OH) 2 D 3 inhibits TNF-α expression in human monocyte derived macrophages

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Purpose We wanted to investigate effects of vitamin D 3 (25(OH)D 3 and 1.25(OH) 2 D 3 ) on inflammatory cytokine expression in both activated and non-activated Mφ. Materials and methods Mononuclear cells, isolated from healthy donor buffy coats were cultured for a 6-day differentiation-period. Fully differentiated Mφ were pre-treated with either 25(OH)D 3 or 1.25(OH) 2 D 3 for (4, 12 or 24 hours) +/-LPS challenge for 4 hours . Gene expression analyses of VDR, Cyp27b1 and pro-inflammatory markers TNF-α, IL-6, NF-κB, MCP-1, was performed using RT-quantitative PCR. TNF-α protein levels from Mφ culture media were analysed by ELISA. Results Both 25(OH)D 3 and 1.25(OH) 2 D 3 significantly inhibited TNF-α expression in both LPS-stimulated and unstimulated Mφ. Also, NF-κB, and to a lesser extend IL-6 and MCP-1 were inhibited. LPS up-regulated Cyp27b1 gene expression which was partly reverted by 1.25 (OH) 2 D 3 . Conclusion These data show anti-inflammatory effects of vitamin D 3 (25(OH)D 3 and 1.25(OH) 2 D 3 ) in human macrophages, and support, that means for targeting high dose vitamin D 3 to the immune system may have beneficial clinical effect in inflammatory conditions.

TidsskriftPLOS ONE
StatusUdgivet - 2019

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