MicroRNA-125b mediates Interferon-γ-induced downregulation of the vitamin D receptor in systemic lupus erythematosus.

ABSTRACT

BACKGROUND: The inflammatory factor interferon (IFN)-γ is related to the occurrence and development of systemic lupus erythematosus (SLE). The vitamin D receptor (VDR) has an anti-inflammatory effect and its downregulation is involved in the onset of SLE. Our previous studies have confirmed that the expression of VDR in SLE peripheral blood mononuclear cells (PBMCs) is downregulated, which is negatively correlated with disease activity and inflammation. However, the mechanism underlying VDR downregulation in SLE is unknown. METHODS: Based on the results of computer simulation analysis, the expression of VDR and four microRNAs (miR-17-3p, miR-34a, miR-346, and miR-125b) in SLE PBMC cells was analyzed under proinflammatory cytokine IFN­Î³ treatment, and miR-125b was identified as the target miRNA. The relationship between IFN­Î³, miR-125b, and VDR was further assessed in THP­1 cells. RESULTS: We showed that IFN­Î³ inhibited the expression of VDR and miR-125b. Further study revealed that VDR mRNA was positively correlated with miR-125b in THP­1 cells after IFN­Î³ intervention. After transfection of miR-125b mimic or inhibitor, the expression of VDR in the miR-125b inhibitor group was lower than in the control group and miR-125b mimic group, while expression in the control group was lower than in miR-125b mimic group. Transfection of miR-125b inhibitor into THP­1 cells could further promote the ability of IFN­Î³ to inhibit VDR. CONCLUSION: The decrease in VDR expression promotes development of inflammation and SLE. These data suggest that miR-125b may mediate inflammatory factor IFN-γ-induced downregulation of VDR in the pathogenesis of SLE.