Interleukin-1β induces apoptosis in annulus fibrosus cells through the extracellular signal-regulated kinase pathway

Abstract

ABSTRACTPurpose: The loss of intervertebral disc (IVD) cells due to excessive apoptosis induced by inflammatory cytokines is a major cause of IVD degeneration. This study aims to explore the mechanism of interleukin-1β (IL-1β)-induced apoptosis of annulus fibrosus cells (AFCs). It's hypothesized that IL-1β induces apoptosis through the extracellular signal-regulated kinase (ERK) pathway in AFCs.Methods: The mRNA and protein expression levels of apoptosis-associated genes were analyzed by quantitative real-time PCR and Western blotting. The apoptotic rate was measured by flow cytometry. Three experimental groups were established, including Control, IL-1β, and IL-1β+U0126 groups, respectively.Results: Increase in the expression of apoptosis-associated genes including B-cell lymphoma-2 associated X (Bax), caspase-3, and caspase-9, and meanwhile, decrease in the expression of B-cell lymphoma-2 (Bcl-2) gene were found in patients with degenerative IVDs. In in vitro tests, both apoptosis and phosphorylated ERK expression in rat AFCs decreased in the IL-1β+U0126 group compared with the IL-1β group. The expression levels of Bax, caspase-3, and caspase-9 in AFCs decreased significantly in the IL-1β+U0126 group compared with those in the IL-1β group. The expression level of Bcl-2, on the other hand, significantly increased.Conclusions: Findings from this study suggest that IL-1β induces apoptosis in AFCs through the ERK pathway, and therefore, ERK inhibition may provide certain protection against the adverse effects of IL-1β.