Potential Involvement of the IL-6/JAK/STAT3 Pathway in the Pathogenesis of Intervertebral Disc Degeneration.
SPINE(2017)
摘要
Study Design. Laboratory study. Objective. To elucidate the potential involvement of the interleukin- 6 (IL-6)/ Janus kinase (JAK)/ signal transducers and activator of transcription (STAT3) pathway in the development of intervertebral disc (IVD) degeneration. Summary of Background Data. IL-6 plays a crucial role in IVD degeneration; however, the downstream intracellular signaling of IL-6 in the IVD is not fully understood. Methods. The expression levels of IL-6 and suppressors of cytokine signaling 3 (SOCS3), a target gene of the IL-6/JAK/ STAT3 pathway, were evaluated in rat and human degenerated IVD samples. The effects of IL-6 on primary rat annulus fibrosus (AF) cells were analyzed using quantitative PCR, immunocytochemistry, and Western blotting. The potential efficacy of a JAK inhibitor, CP690,550, in neutralizing the effect of IL-6 was evaluated in vitro. Results. A high expression of IL-6 and SOCS3 was observed in both rat and human degenerated IVD samples. In rat AF cells, IL-6 markedly induced the phosphorylation of STAT3 and the expression of cyclooxygenase-2 and matrix metalloprotease-13. CP690,550 significantly suppressed the phosphorylation of STAT3 and offset the catabolic effect of IL-6 in rat AF cells. Conclusion. Our results suggest that the IL-6/ JAK/ STAT3 pathway is involved in the pathogenesis of IVD degeneration and that CP690,550 suppresses the catabolic effect of the IL-6 in the IVD.
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关键词
cytokine signaling,interleukin-6,intervertebral disc degeneration,Janus kinase,pathogenesis,signal transducers
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