c-Jun氨基末端激酶信号通路抑制对白细胞介素-1诱导的大鼠椎间盘纤维环细胞基因表达的影响

Effect of c-Jun N-terminal Kinase Inhibition on Gene Expression Induced by Interleukin-1 in Annulus Fibrosus Cells in Rats

目的研究c-Jun氨基末端激酶(JNK)信号通路抑制对白细胞介素-1(IL-1)诱导的大鼠椎间盘纤维环细胞基因表达的影响,为阻止椎间盘退变提供新的治疗靶点。方法分离培养大鼠尾椎纤维环细胞,IL-1刺激纤维环细胞后,Western blot检测JNK信号通路的激活;传代的纤维环细胞培养48 h后,以IL-1(10 ng/ml)加或不加JNK通路抑制剂SP600125刺激24 h,Real-Time PCR检测JNK通路抑制对IL-1诱导的大鼠纤维环细胞基因表达的影响。结果 JNK通路抑制可显著抑制IL-1引起的诱导性一氧化氮合酶(iNOS)、白细胞介素-6(IL-6)、环氧合酶-2(Cox-2)和基质金属蛋白酶(MMP)-3、MMP-13表达上调,同时,可显著逆转IL-1引起的Ⅰ型胶原和胰岛素样生长因子-1(IGF-1)基因表达下调。结论 JNK通路抑制可作为阻断IL-1诱导的椎间盘退变的治疗靶点。

Objective To determine the role of c-Jun N-terminal kinase （JNK） signaling in annulus fibrosus cells response to interleukin （IL）-I. Methods Rat annulus fibrosus ceils cultured in monolayer were exposed to IL-1, with or without JNK inhibition by SP600125. RNA was isolated for Real-Time polymerase chain reaction （PCR） after 24 h stimulation. Results IL-1 upregulation of mRNA for inducible nitric oxide synthase （iNOS）, IL-6, cyclooxygenase （Cox）-2, matrix metalloproteinase （MMP）-3, MMP-13 were blunted by JNK inhibition, while downregulation of collagen I and insulin-like growth factor （IGF）-I were also reversed by JNK inhibition. Conclusion JNK signaling inhibi- tion can be a therapeutic target for blocking intervertebral disc degeneration induced by IL- 1.