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

الملخص EN

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.