Total glucosides of paeony protects THP-1 macrophages against monosodium urate-induced inflammation via MALAT1/miR-876-5p/NLRP3 signaling cascade in gouty arthritis

• Published in: Biomedicine & pharmacotherapy 2021-06, Vol.138, p.111413-111413, Article 111413
• Main Authors: Meng, Qingliang, Meng, Wanting, Bian, Hua, Zheng, Fuzeng, Gu, Huimin, Zuo, Ruiting, Miao, Xiyun, Zhou, Zipeng, Wang, Liying, Wen, Zhike, Ma, Junfu, Su, Xiao
• Format: Article
• Language: English
• Subjects: Gouty arthritis; MALAT1; MiR-876-5p; Monosodium urate; NLRP3; Total glucosides of paeony
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2021.111413

Monosodium urate (MSU)-mediated inflammatory response is a crucial inducing factor in gouty arthritis. Here, we explored the underlying mechanism of total glucosides of paeony (TGP) in MSU-induced inflammation of THP-1 macrophages in gouty arthritis. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to detect cell viability. Enzyme-linked immunosorbent assay (ELISA) was utilized to measure the production of interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α). Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot assay were conducted to determine RNA and protein expression. Dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay and RNA pull down assay were used to confirm the interaction between miR-876-5p and MALAT1 or NLR family pyrin domain containing 3 (NLRP3). MSU-induced damage and inflammatory response in THP-1 macrophages were alleviated by the treatment of TGP in a dose-dependent manner. Overexpression of NLRP3 or MALAT1 reversed the protective effects of TGP in MSU-induced THP-1 macrophages. The binding relation between miR-876-5p and MALAT1 or NLRP3 was identified in THP-1 macrophages. MALAT1 up-regulated the expression of NLRP3 by sponging miR-876-5p in THP-1 macrophages. TGP suppressed MSU-induced inflammation in THP-1 macrophages through regulating MALAT1/miR-876-5p/NLRP3 axis. TGP suppressed MSU-induced activation of TLR4/MyD88/NF-κB pathway through regulating MALAT1/miR-876-5p/NLRP3 axis. In conclusion, TGP suppressed MSU-induced inflammation in THP-1 macrophages through regulating MALAT1/miR-876-5p/NLRP3 axis and TLR4/MyD88/NF-κB pathway, suggesting that TGP was a promising active ingredient for gouty arthritis treatment.