Effect of IL-1β on apoptosis of synovial cells in rheumatoid arthritis rats via the NF-κB pathway.

Abstract

The aim of this study was to investigate the role of interleukin-1β (IL-1β) in the apoptosis of synovial cells in rheumatoid arthritis (RA) rats, and to explore the underlying mechanism. The apoptosis of the synovial cells in RA rats in the IL-1β group and the control group was analyzed by scoring under an electron microscope. The expressions of cleaved-poly (ADP-ribose) polymerase (PARP), PARP and anti-apoptosis gene products in synovial cells of IL-1β treated RA rats were explored as well. Meanwhile, the expressions of B-cell lymphoma 2 (Bcl-2), Bcl-xL, and Active-Caspase3 in the synovial cells of RA rats with IL-1β treatment were evaluated by the Western blotting. To further clarify the relationship between IL-1β and the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway in the synovial cells of RA rats, the expressions of NF-κB regulated the gene products of matrix metalloproteinase-3 (MMP-3), MMP-9, cyclooxygenase-2 (Cox-2), and vascular endothelial growth factor (VEGF) in synovial cells of RA rats after that we investigated the treatment with IL-1β (was investigated). In addition, the expression of NF-κB in the synovial cells of RA rats treated with IL-1β was determined. The results showed that, compared with the control group, IL-1β treatment significantly increased the number of apoptotic cells. This meant that IL-1β treatment could promote the apoptosis of the synovial cells (p<0.05). IL-1β treatment significantly promoted the expression level of cleaved-PARP (p<0.05). However, it remarkably reduced the expressions of Bcl-2 and Bcl-xL (p<0.05). Meanwhile, the level of the active-Caspase3 in the synovial cells of RA rats treated with IL-1β was significantly enhanced (p<0.01). In comparison with the control group, the IL-1β group exhibited significantly elevated expressions of NF-κB-regulated gene products in the synovial cells of RA rats (p<0.01). Besides, the positive markers of the activated NF-κB were detected in the synovial cells of RA rats in the IL-1β group and the control group. The results demonstrated that they were mainly located in the nucleus of the IL-1β group. IL-1β can promote the apoptosis of the synovial cells in RA rats via the NF-κB pathway.