• Turk J Med Sci · Aug 2021

    The inhibition of Src kinase suppresses the production of matrix metalloproteinases in from synovial fibroblasts and inhibits MAPK and STATs pathways

    • Demet Yalçın Kehribar, Metin Özgen, Servet Yolbaş, Ahmet Yıldırım, Ebru Önalan Etem, Osman Çiftçi, İbrahim Hanifi Özercan, and Süleyman Serdar Koca.
    • Department of Internal Medicine, Faculty of Medicine, Ondokuz Mayıs University, Samsun, Turkey
    • Turk J Med Sci. 2021 Aug 30; 51 (4): 2142-2149.

    Background/AimThe purpose of this study was to investigate the antiarthritic potentials of the inhibition of Src kinase in vivo and in vitro settings.Materials And MethodsArthritis was induced by intradermal injection of chicken type II collagen combined with incomplete Freund’s adjuvant (collagen induced arthritis [CIA] model) in Wistar albino rats. One day after the onset of arthritis, dasatinib, a potent Src kinase inhibitor, (5 mg/kg/day) was given via oral gavage. Tissue Src, Fyn, MAPK and STAT mRNA expressions were determined by real-time polymerase chain reaction. On the other hand, fibroblast like synoviocytes (FLSs) were harvested patients with rheumatoid arthritis (RA) undergoing surgical knee joint replacement. FLSs were stimulated with cytokines and dasatinib was added in different concentrations. MMP –1, –3, and –13 levels in FLSs culture were determined by ELISA.ResultsThe tissue mRNA expressions of Src, Fyn, MAPK and STATs were increased in the arthritis CIA group compared to the control group. Their mRNA expressions in the CIA + dasatinib group were decreased and similar in the control group. In in vitro setting, MMP –1, –3, and –13 expressions from FLSs induced by IL-1β and TNF-α were increased, while dasatinib suppressed their productions from FLSs.ConclusionThe present study shows that the inhibition of Src kinase has antiarthritic potentials in both in vivo and in vitro settings. Src kinase inhibition may be candidate to further research in human RA.This work is licensed under a Creative Commons Attribution 4.0 International License.

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