PMID- 30542493 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200929 IS - 1792-0981 (Print) IS - 1792-1015 (Electronic) IS - 1792-0981 (Linking) VI - 16 IP - 6 DP - 2018 Dec TI - Protective effect of avicularin on rheumatoid arthritis and its associated mechanisms. PG - 5343-5349 LID - 10.3892/etm.2018.6872 [doi] AB - The present study aimed to investigate the effect of avicularin on rheumatoid arthritis (RA) in vitro, and additionally explore the molecular mechanism. To perform this investigation, an in vitro model of RA was established by treatment of the human RA synovial MH7A cell line with tumor necrosis factor-alpha (TNF-alpha). MH7A cells were then treated with various concentrations (10, 30, 100 and 300 microM) of avicularin. Then, the levels of inflammatory factors [interleukin (IL)-1beta, IL-6, IL-8, matrix metalloproteinase (MMP)-1 and MMP-13] were measured by ELISA. Cell viability and apoptosis were detected using an MTT assay and flow cytometry, respectively. In addition, the expression levels of genes and proteins were determined reverse transcription quantitative polymerase chain reaction and western blot analysis. The results of the present study indicated that avicularin significantly decreased the levels of inflammatory factors (IL-1beta, IL-6, IL-8, MMP-1 and MMP-13), previously increased by TNF-alpha, in a dose-dependent manner. Concurrently, avicularin inhibited the mRNA and protein expression levels of iNOS and COX-2 increased by TNF-alpha. It was also identified that TNF-alpha administration significantly promoted MH7A cell viability and inhibited cell apoptosis, and avicularin treatment dose-dependently inhibited MH7A cell viability and induced cell apoptosis. In addition, these data suggested that avicularin prevented the activation of the mitogen-activated protein kinase kinase (MEK)/nuclear factor kappa light-chain-enhancer of activated B-cells (NF-kappaB) pathway activated by TNF-alpha. Taken together, these results demonstrated that avicularin may inhibit the inflammatory response, prevent cell viability and induce apoptosis in human RA synovial cells through preventing the activation of the MEK/NF-kappaB pathway. FAU - Wang, Wei AU - Wang W AD - Department of Rheumatology and Nephrology, Hangzhou Red Cross Hospital, Hangzhou, Zhejiang 310003, P.R. China. FAU - Zheng, Hongxia AU - Zheng H AD - Department of Rheumatology and Nephrology, Hangzhou Red Cross Hospital, Hangzhou, Zhejiang 310003, P.R. China. FAU - Zheng, Minwei AU - Zheng M AD - Department of Rheumatology and Nephrology, Hangzhou Red Cross Hospital, Hangzhou, Zhejiang 310003, P.R. China. FAU - Liu, Xiaoxian AU - Liu X AD - Department of Rheumatology and Nephrology, Hangzhou Red Cross Hospital, Hangzhou, Zhejiang 310003, P.R. China. FAU - Yu, Jianning AU - Yu J AD - Department of Rheumatology and Nephrology, Hangzhou Red Cross Hospital, Hangzhou, Zhejiang 310003, P.R. China. LA - eng PT - Journal Article DEP - 20181017 PL - Greece TA - Exp Ther Med JT - Experimental and therapeutic medicine JID - 101531947 PMC - PMC6257287 OTO - NOTNLM OT - avicularin OT - inflammatory response OT - rheumatoid arthritis OT - synovial fibroblasts EDAT- 2018/12/14 06:00 MHDA- 2018/12/14 06:01 PMCR- 2018/10/17 CRDT- 2018/12/14 06:00 PHST- 2018/05/17 00:00 [received] PHST- 2018/08/31 00:00 [accepted] PHST- 2018/12/14 06:00 [entrez] PHST- 2018/12/14 06:00 [pubmed] PHST- 2018/12/14 06:01 [medline] PHST- 2018/10/17 00:00 [pmc-release] AID - ETM-0-0-6872 [pii] AID - 10.3892/etm.2018.6872 [doi] PST - ppublish SO - Exp Ther Med. 2018 Dec;16(6):5343-5349. doi: 10.3892/etm.2018.6872. Epub 2018 Oct 17.