miR-98 Modulates Cytokine Production from Human PBMCs in Systemic Lupus Erythematosus by Targeting IL-6 mRNA

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-1β, 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-1β, 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.

Prediction and analysis of microRNAs involved in COVID-19 inflammatory processes associated with the NF-kB and JAK/STAT signaling pathways

“…The results of a study on the peripheral blood mononuclear cells (PBMCs) samples of systemic lupus erythematosus (SLE) patients showed that miR-98-5p directly targeted IL-6 and inhibited the production of inflammatory cytokines and cell proliferation through IL-6/STAT3 pathway [97] . Moreover, the results of a dual luciferase reporter assay in human adipose stem cells indicated that miR-223-3p regulated the expression of inflammatory cytokines IL-6 and STAT3 (J.…”

Immunological Involvement of MicroRNAs in the Key Events of Systemic Lupus Erythematosus

“…This summary of the current research results has shown that various, ubiquitous and functional miRNAs are involved in most immunological events leading to SLE. The upregulation of let-7c contributes to proinflammatory features of DCs in SLE ( 23 ); MiR-7 is associated with the overactivation of B cells and subsequent autoantibody production ( 37 ); MiR-21 up-regulation contributes to T cell hyperactivity ( 51 ); MiR-34a is associated with defection of Tregs and immune tolerance breakdown ( 65 ); Transfection of miR-98 alleviates the increased production of inflammatory cytokines ( 96 ). Different miRNAs can target the same mRNA, and one miRNA can target multiple mRNAs.…”

Exploring the Role of Non-Coding RNAs in the Pathophysiology of Systemic Lupus Erythematosus

“…MiR-98 modulates STAT3 phosphorylation through the regulation of IL-6 expression. Thus, miR-98 can amend STAT3-associated cell proliferation and the release of pro-inflammatory cytokines in patients with SLE [ 40 ]. The downregulation of miR-98 has also been reported in SLE CD4+ T cells, while Fas levels were enhanced [ 41 ].…”