当前位置： SCI文献检索 > INTERNATIONAL IMMUNOPHARMACOLOGY期刊下所有文献 > 1,25‑Dihydroxyvitamin D regulates macrophage polarization and ameliorates experimental inflammatory bowel disease by suppressing miR-125b.

1,25‑Dihydroxyvitamin D regulates macrophage polarization and ameliorates experimental inflammatory bowel disease by suppressing miR-125b.

Abstract：

:Macrophages are highly plastic cells. Depending on stimulation, macrophages rapidly polarize to functionally distinct phenotypes that are involved in the pathogenesis of inflammatory bowel disease (IBD). 1,25‑Dihydroxyvitamin D (1,25(OH)2D3) has immunomodulatory activity, and 1,25(OH)2D3 deficiency is correlated with autoimmune diseases, especially IBD. This study aimed to explore whether 1,25(OH)2D3 modulates macrophage polarization in inflammation. Peripheral blood mononuclear cells and colitis mice were treated with 1,25(OH)2D3. Macrophages were transfected with siRNA-vitamin D receptor (VDR) or miR-125b mimic or inhibitor, and 1,25(OH)2D3-pretreated colitis mice were injected with a miR-125b agomir. The distribution of macrophage subsets and macrophage subtype characteristics was analyzed. As expected, 1,25(OH)2D3 transformed lipopolysaccharide-induced M1 macrophages to the M2 subset, downregulated tumor necrosis factor-α and interleukin (IL)-6 expression and interferon regulatory factor 5 (IRF5) phosphorylation, and upregulated IL-10, arginase-1, VDR, and IRF4 expression. SiRNA-VDR and miR-125b mimic significantly impaired 1,25(OH)2D3 activity. In colitis mice, 1,25(OH)2D3 pretreatment ameliorated disease activity, converted M1 macrophages to the M2 subtype, suppressed IRF5 phosphorylation, and increased IRF4 expression in lamina propria mononuclear cells (LPMC). miR-125b agomir injections reversed 1,25(OH)2D3 action. Collectively, the results demonstrate that 1,25(OH)2D3 downregulates miR-125b expression and promotes M1 macrophage polarization to the M2 subtype. 1,25(OH)2D3 pretreatment ameliorated colitis by restoring the LPMC macrophage subtype balance.

journal_name

Int Immunopharmacol

journal_title

International immunopharmacology

authors

Zhu X,Zhu Y,Li C,Yu J,Ren D,Qiu S,Nie Y,Yu X,Xu X,Zhu W

doi

10.1016/j.intimp.2018.12.015

subject

Has Abstract

pub_date

2019-02-01 00:00:00

pages

106-118

eissn

1567-5769

issn

1878-1705

pii

S1567-5769(18)30706-9

journal_volume

67

pub_type

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