Periplocin induces apoptosis and inhibits inflammation in rheumatoid arthritis fibroblast-like synoviocytes via nuclear factor kappa B pathway.

Abstract

Apoptotic resistance and excessive proliferation of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs) stimulated by inflammation could lead to distal joint destruction and bone damage. Periplocin could promote apoptosis, resist proliferation, and reduce inflammation. However, the effect and mechanism toward periplocin in proliferation and inflammation of RA-FLSs remain unclear. The role of tumor necrosis factor (TNF)-α induced proliferation and expression of inflammatory cytokines in RA-FLSs was established. Our studies noted that cell viability of TNF-α-induced RA-FLSs was inhibited in periplocin treatment via dose-response, whereas cell apoptosis of RA-FLSs was triggered by dose-dependent effect of periplocin. Bcl-2 protein, one of the apoptotic regulators, was downregulated, while other regulators of apoptosis, including BAX, cleaved caspase-3, and cleaved caspase-9, were upregulated in RA-FLSs under periplocin treatment. In addition, periplocin decreased the TNF-α-induced mRNA and protein expression levels of interleukin (IL)-1β and IL-6 in RA-FLSs in a dose-dependent way. Finally, the increased levels of phospho (p)-inhibitor of kappa B (IκBα)/IκBα and p-NF (nuclear factor)-κB/nuclear factor kappa B (NF-κB) ratio of RA-FLSs stimulated by TNF-α were decreased by periplocin treatment. Taken together, periplocin treatment decreased cell viability and cytokines expression and promoted cell apoptosis of TNF-α-induced RA-FLSs through inhibition of NF-κB signaling pathway, providing a potential therapeutic approach for RA.