Astragalus polysaccharides inhibits cell growth and pro-inflammatory response in IL-1 β-stimulated fibroblast-like synoviocytes by enhancement of autophagy via PI3K/AKT/mTOR inhibition

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-1 β-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 expres sion 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 conc luded 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.
Source: Apoptosis - Category: Molecular Biology Source Type: research