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1,25-二羟维生素 D3 通过上调 T 细胞免疫球蛋白黏蛋白-3 的表达诱导巨噬细胞向 M2 极化。

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

机构信息

Department of Pediatrics, Tianjin First Center Hospital, Tianjin 300192, P.R. China.

Department of Transplantation Surgery, Tianjin First Center Hospital, Tianjin 300192, P.R. China.

出版信息

Mol Med Rep. 2019 May;19(5):3707-3713. doi: 10.3892/mmr.2019.10047. Epub 2019 Mar 15.

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.

摘要

巨噬细胞极化在免疫调节中起着重要作用,而 T 细胞免疫球蛋白黏蛋白 3(Tim-3)可调节其极化。本研究旨在探讨 1,25-二羟维生素 D3 [1,25(OH)2D3] 在巨噬细胞极化中的作用。采用质粒转染技术制备沉默或过表达 Tim-3 基因的 RAW264.7 细胞。ELISA 法检测巨噬细胞分泌的炎症因子水平。Western blot 分析检测蛋白水平。逆转录定量聚合酶链反应检测 mRNAs 表达水平。结果表明,1,25(OH)2D3 上调 Tim-3 水平并促进白细胞介素(IL)-10 的分泌。还观察到 1,25(OH)2D3 增加转化生长因子-β水平并抑制肿瘤坏死因子-α和 IL-6。结果还表明,Tim-3 基因沉默诱导巨噬细胞向经典激活型巨噬细胞(M1)极化,而过表达 Tim-3 基因则诱导巨噬细胞向替代激活型巨噬细胞(M2)极化。1,25(OH)2D3 处理可上调巨噬细胞中 Tim-3 的表达水平,从而促进细胞向 M2 极化并抑制向 M1 极化。本研究数据表明,Tim-3 可能诱导巨噬细胞向 M2 极化,而 1,25(OH)2D3 通过上调 Tim-3 产生免疫抑制作用。

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