MiR-98 Modulates Cytokine Production from Human PBMCs in Systemic Lupus Erythematosus by Targeting IL-6 mRNA. (1st December 2019)

• Record Type: Journal Article
• Authors: Yuan, Shiwen; Tang, Chun; Chen, Dongying; Li, Fangfei; Huang, Mingcheng; Ye, Jinghua; He, Zhixiang; Li, Weinian; Chen, Yi; Lin, Xiaojun; Wang, Xiaodong; Cai, Xiaoyan
• Other Names: Zhang Minggang Guest Editor.
• Is Part Of: Journal of immunology research. Volume 2019(2019)
• Publication Date: 2019-12-01
• Subjects: Immunology -- Periodicals; Immunology -- Research -- Periodicals; 616.07905
• DOI: 10.1155/2019/9827574
• Languages: English
• ISSNs: 2314-8861

Abstract

Abstract : Objective . There is evidence that interleukin-6 (IL-6) upregulation plays a critical role in immunopathology of systemic lupus erythematosus (SLE). MicroRNA- (miRNA-) 98 was predicted to bind with the 3 ′ -untranslated region (3 ′ -UTR) of IL-6 gene. We hypothesized miR-98 through its regulation of IL-6 gene expression to influence cytokine production from peripheral blood mononuclear cells (PBMCs) in SLE. Methods. The expression of miR-98 and IL-6 mRNA in the PBMCs of 41 SLE patients and 20 healthy controls (HC) was detected by quantitative reverse transcription PCR (qRT-PCR). The correlations between miR-98 expression and clinical features were evaluated. Luciferase reporter assay was performed to identify miR-98 targets. miR-98 mimics, miR-98 inhibitor, and IL-6 overexpression vector were generated. Cell viability of PBMCs was assessed using MTT assay. Gene expression and protein level were determined by qRT-PCR and Western blotting. TNF- α, IL-8, IL-1 β, and IL-10 levels in cultured supernatants were quantified using ELISA. Results. The expression of miR-98 was downregulated in PBMCs of SLE patients, and its expression is negatively associated with IL-6 levels. miR-98 expression was correlated with disease activity, lupus nephritis, and anti-dsDNA antibody. IL-6 mRNA was a target gene of miR-98. IL-6 overexpression promoted the proliferation of PBMCs and increased the levels of TNF- α, IL-8, IL-1 β, and IL-10. Those effects were further enhanced by miR-98 inhibitor, while were suppressed by miR-98 mimics. miR-98 regulated the levels of STAT3 phosphorylation via its target gene IL-6. Conclusion. The current study revealed that miR-98 could ameliorate STAT3-mediated cell proliferation and inflammatory cytokine production via its target gene IL-6 in patients with SLE. These results suggest that miR-98 might serve as a potential target for SLE treatment and other IL-6-mediated diseases.