1,25‑Dihydroxy‑Vitamin D3 induces macrophage polarization to M2 by upregulating T‑cell Ig‑mucin‑3 expression.

Abstract

Macrophage polarization serves an important role in immune regulation that is regulated by T-cell immunoglobulin-mucin-3 (Tim-3). The objective of the present study was to explore the role of 1,25-dihydroxy-vitamin D3 [1,25(OH)2D3] in macrophage polarization. Plasmid transfection techniques were applied to prepare RAW264.7 cells with silenced or overexpressed Tim-3 gene. ELISAs were used to examine the level of inflammatory factors secreted by macrophages. Proteins levels were determined by western blot analysis. mRNAs expression levels were assessed using reverse transcription quantitative polymerase chain reaction. It was identified that 1,25(OH)2D3 upregulated Tim-3 levels and promoted the secretion of interleukin (IL)-10. 1,25(OH)2D3 was also observed to increase the level of transforming growth factor-β and to inhibit tumor necrosis factor-α and IL-6. The results also suggested that Tim-3 gene silencing induced macrophages polarization to classically activated macrophages (M1), and that overexpression of the Tim-3 gene induced macrophage polarization to alternatively activated macrophages (M2). 1,25(OH)2D3 treatment upregulated the expression level of Tim-3 in macrophages, which promoted cell polarization to M2 and inhibited polarization to M1. The data from the present study indicated that Tim-3 may induce macrophage polarization to M2, and that 1,25(OH)2D3 produced immunosuppressive effects by upregulating Tim-3.