The hyperplastic growth of rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLSs) and inflammatory response are pathological hallmarks of RA. It has been reported that Astragalus polysaccharides (APS) possess appreciable anti-inflammatory activity against adjuvant-induced arthritis. Nevertheless, little is known about the role and detailed mechanism underlying the therapeutic effects of APS in RA. This study demonstrated that administration of APS dose-dependently impaired cell viability, increased cell apoptosis by decreasing Bcl-2 expression, increasing Bax expression and Caspase3 activity in IL-1β-stimulated RSC-364 cells and RA-FLS. Simultaneously, IL-1β-induced production of pro-inflammatory cytokines IL-6 and TNF-α was significantly decreased after APS treatment. Furthermore, preconditioning with APS dramatically enhanced autophagy activity by increasing Beclin-1 and LC3II/LC3I expression coupled with decreasing p62 expression and augmenting the number of LC3 puncta in IL-1β-stimulated RSC-364 cells. More importantly, autophagy inhibitor 3-methyladenine (3-MA) partly abolished APS-triggered inhibitory effects on cell growth and production of pro-inflammatory cytokines. APS also repressed the activation of PI3K/Akt/mTOR signaling pathway in IL-1β-stimulated RSC-364 cells. Moreover, treatment with insulin-like growth factor-1 (IGF-1), an activator of PI3K/Akt signaling, partly reversed the therapeutic effects of APS in IL-1β-stimulated RSC-364 cells. Collectively, we concluded that APS might attenuate the pathological progression of RA by exerting the pro-apoptotic and anti-inflammatory effects in IL-1β-stimulated FLSs by regulating the PI3K/AKT/mTOR-autophagy pathway.
Apoptosis – Springer Journals
Published: Jun 28, 2017
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