Mechanisms by which MicroRNA-146a (miR-146a) regulate the inflammatory response in SLE
Exp Ther Med. 2019 Oct;18(4):3078-3084
Authors: Zhou C, Zhao L, Wang K, Qi Q, Wang M, Yang L, Sun P, Mu H
MicroRNA (miR)-146a levels are reduced in peripheral blood mononuclear cells of patients with systemic lupus erythematosus (SLE); however, its function is not well understood. The present study investigated the role of miR-146a in the regulation of lipopolysaccharide (LPS)-induced inflammation in THP-1 cells. A miR-146a mimic and an inhibitor were used to overexpress and downregulate miR-146a expression, respectively. Reverse transcription-quantitative PCR and western blot analyses were performed to evaluate interleukin (IL)-1 receptor-associated kinase 1 (IRAK1) expression, and western blot analysis was applied to assess nuclear factor-κB activation by analyzing p65 subunit levels in the nucleus. To investigate the effects of miR-146a on LPS-induced inflammation, IL-6 and tumor necrosis factor-α (TNF-α) levels were also measured using ELISA. The results of the present study revealed thatmiR-146a overexpression significantly reduced IRAK1 expression, reduced p65 levels in the nucleus and reduced IL-6 and TNF-α levels in the supernatant of the cell culture medium of THP-1 cells following LPS treatment. Luciferase assays confirmed IRAK1 to be a direct target of miR-146a in THP-1 cells. In conclusion, miR-146a may regulate IRAK1 expression and inhibit the activation of inflammatory signals and secretion of pro-inflammatory cytokines. The present study revealed, at least in part, the mechanisms by which miR-146a regulate the inflammatory response in SLE.
PMID: 31572547 [PubMed]