MicroRNA-146a inhibits NF-[kappa]B activation and pro-inflammatory cytokine production by regulating IRAKI expression in THP-1 cells

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 TH...

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Published in:Experimental and therapeutic medicine 2019-10, Vol.18 (4), p.3078
Main Authors: Zhou, Chunlei, Zhao, Lan, Wang, Kai, Qi, Qianru, Wang, Meng, Yang, Lei, Sun, Ping, Mu, Hong
Format: Article
Language:English
Subjects:
Analysis
Cytokines
Enzyme-linked immunosorbent assay
Inflammation
Interleukins
Luciferase
Lupus
Lupus erythematosus
MicroRNA
Mitogens
Necrosis
Pharmaceutical industry
Polymerase chain reaction
Scientific equipment industry
Systemic lupus erythematosus
Tumors
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Summary: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-[kappa]B 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-[alpha] (TNF-[alpha]) 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-[alpha] levels in the supernatant of the cell culture medium of THP-1 cells following LPS treatment. Luciferase assays confirmed IRAKI 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. Key words: microRNA-146a, interleukin-1 receptor-associated kinase 1, nuclear factor-KB, interleukin-6, tumor necrosis factor-[alpha], systemic lupus erythematosus
ISSN:1792-0981
DOI:10.3892/etm.2019.7881