IL-6 modulates alpha-smooth muscle actin expression in dermal fibroblasts from IL-6-deficient mice
IL-6 modulates alpha-smooth muscle actin expression in dermal fibroblasts from IL-6-deficient mice
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DOI：
10.1038/sj.jid.5700109
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发表时间：
2006-03-01
影响因子：
6.5
通讯作者：
Tomasek, James J.
中科院分区：
文献类型：
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作者：
Gallucci, Randle M.;Lee, Eric G.;Tomasek, James J.
IL-6缺陷（IL-6 KO）小鼠显示皮肤伤口闭合显着延迟。肌成纤维细胞是伤口闭合的主要介质，α-平滑肌肌动蛋白（α-SMA）是成纤维细胞分化为肌成纤维细胞表型的标志物。收集来自IL-6KO和野生型小鼠的伤口，直至受伤后6天。发现在IL-6KO小鼠的伤口中，α-SMA mRNA的表达增加至创伤后48小时，但在72小时时降低至野生型水平以下。IL-6KO真皮成纤维细胞的重组IL-6处理显示α-SMA mRNA和蛋白的诱导在1 ng/ml细胞因子时达到峰值，但在较高浓度时下降。放线菌素D处理的成纤维细胞培养物表明，重组小鼠IL-6（rmIL-6）诱导的α-SMA mRNA似乎主要是转录调节，细胞外信号调节激酶1/2激酶，但不是信号转导和转录激活因子3容易磷酸化rmIL-6处理的IL-6KO成纤维细胞。在rmIL-6处理的IL-6KO成纤维细胞中也观察到IL-6R信号传导抑制剂细胞因子信号传导抑制蛋白（SOCS）3 mRNA表达的剂量反应性增加。这些数据表明α-SMA表达在IL-6KO小鼠中失调。在IL-6KO小鼠的成纤维细胞中，rmIL-6诱导的α-SMA表达似乎是转录调节的，依赖于JAK1激酶，并且可能由于SOCS3表达增加而下调。
IL-6 deficient (IL-6KO) mice display significantly delayed cutaneous wound closure. Myofibroblasts are the primary mediators of wound closure, and alpha-smooth muscle actin (alpha-SMA) is a marker of fibroblast differentiation to the myofibroblast phenotype. Wounds from IL-6KO, and wild-type mice were collected up to 6 days following wounding. Expression of alpha-SMA mRNA was found to be increased in wounds of IL-6KO mice up to 48 hours post wounding, but decreased below wild-type levels by 72 hours. Recombinant IL-6 treatment of IL-6KO dermal fibroblasts showed an induction of alpha-SMA mRNA and protein peaking at 1 ng/ml cytokine, but declining at higher concentrations. Actinomycin-D treatment of fibroblast cultures indicated that recombinant mouse IL-6 (rmIL-6) induction of alpha-SMA mRNA appeared to be primarily transcriptionally regulated, and extracellular signal-regulated kinase 1/2 kinase, but not signal transducers and activators of transcription 3 was readily phosphorylated in rmIL-6 treated IL-6KO fibroblasts. A dose-response increase in the mRNA expression of the IL-6R signaling inhibitor protein suppressors of cytokine signaling (SOCS) 3 was also noted in rmIL-6-treated IL-6KO fibroblasts. These data indicate that a-SMA expression is dysregulated in IL-6KO mice. The expression of alpha-SMA induced by rmIL-6 in fibroblasts from IL-6KO mice appears to be transcriptionally modulated, dependent on JAK1 kinase, and possibly downregulated as a result of increased SOCS3 expression.