Brucine inhibits TNF‑α‑induced HFLS‑RA cell proliferation by activating the JNK signaling pathway

Tang,Min; Zhu,Wei‑Ji; Yang,Zu‑Cheng; He,Cheng‑Song

doi:10.3892/etm.2019.7582

Brucine inhibits TNF‑α‑induced HFLS‑RA cell proliferation by activating the JNK signaling pathway

Authors:
- Min Tang
- Wei‑Ji Zhu
- Zu‑Cheng Yang
- Cheng‑Song He
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Affiliations: Department of Rheumatology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China, The Health Center Hospital of Tongtan, Luzhou, Sichuan 646000, P.R. China
Published online on: May 15, 2019 https://doi.org/10.3892/etm.2019.7582
Pages: 735-740

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Abstract

Rheumatoid arthritis (RA) is a diffuse connective tissue disease. Brucine selectively inhibits cell immunity, immune hypersensitivity and induces apoptosis. The current study aimed to investigate effects of brucine on human fibroblast‑like synoviocytes (HFLS) of RA and to clarify associated molecular mechanisms. HFLS‑RA were treated with tumor necrosis factor (TNF)‑α prior to treatment with brucine at carrying concentrations. Cell Counting Kit‑8 assays were performed to evaluate HFLS‑RA proliferation. Western blot assays were employed to examine c‑Jun N‑terminal kinase (JNK) expression and phosphorylation in TNF‑α‑induced HFLS‑RA. An association between brucine treatment and JNK phosphorylation was assessed by employing a linear regression analysis. The results suggested that low doses of brucine (0.125 and 0.25 mg/ml) significantly reversed proliferation effects induced by TNF‑α, however, final cell viabilities were increased compared with the untreated control (P>0.05 and P<0.05, respectively). High brucine doses (≥0.5 mg/ml) significantly reversed TNF‑α‑induced proliferation and further inhibited viability compared with the untreated control (P<0.05). Regarding JNK expression, there were no significant differences among the brucine treatment, and between the Control and the TNF‑α groups (P>0.05). Brucine treatment significantly decreased JNK phosphorylation compared with the TNF‑α group (P<0.05). JNK specific inhibitor, SP600125, significantly inhibited brucine‑induced cell viability enhancement compared with the brucine‑treated groups without inhibitor (P<0.05). A linear regression analysis suggested that brucine was associated with JNK phosphorylation in TNF‑α‑treated HFLS‑RA. In conclusion, brucine significantly inhibited TNF‑α‑induced HFLS‑RA proliferation by activating the JNK signaling pathway. Therefore, brucine may have potential clinical applications in the treatment of RA.

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