miR-101-3p negatively regulates inflammation in systemic lupus erythematosus via MAPK1 targeting and inhibition of the NF-κB pathway

Systemic lupus erythematosus (SLE) is an autoimmune disease often used as a model in genomics research. The downregulation of microRNA-101-3p (miR-101-3p) participates in the progression of SLE, although the underlying mechanisms remain to be elucidated. The present study aimed to evaluate the specific roles of miR-101-3p in the SLE inflammatory response and its potential mechanisms. Reverse transcription-quantitative (RT-q) PCR was used to profile miR-101-3p expression in the peripheral blood mononuclear cells (PBMCs) from 40 female patients with SLE and 20 female healthy volunteers. The interactions between miR-101-3p and MAPK1 were identified and evaluated using dual-luciferase reporter and RNA pull-down assays. The levels of IL-10 and IFN-gamma were evaluated by enzyme-linked immunosorbent assay. The expression of NF-kappa B p65 and phosphorylated I kappa B alpha were evaluated using western blotting. miR-101-3p expression was demonstrated to be downregulated in SLE PBMCs. miR-101-3p negatively regulated IL-10 and IFN-gamma expression in SLE samples and was demonstrated to target MAPK1. Increases in MAPK1 expression eliminated miR-101-3p inhibition of IL-10 and IFN-gamma. MAPK1 activated the NF-kappa B pathway in SLE PBMCs and this activation was inhibited when miR-101-3p was overexpressed. In addition, treatment with BAY11-7085 (NF-kappa B activator) was demonstrated to reverse the inhibitory effects of miR-101-3p expression on both IL-10 and IFN-gamma in SLE PBMCs. BAY11-7082 also markedly reduced MAPK1-induced increases in IL-10 and IFN-gamma in SLE PBMCs. miR-101-3p overexpression attenuated the inflammatory response in SLE PBMCs by inhibiting the expression of MAPK1 and blocking the NF-kappa B pathway. The results revealed a novel regulatory mechanism in SLE inflammation and offer a new direction for the development of SLE treatments.