The pro-inflammatory cytokine IL-22 up-regulates keratin 17 expression in keratinocytes via STAT3 and ERK1/2.

The pro-inflammatory cytokine IL-22 up-regulates keratin 17 expression in keratinocytes via STAT3 and ERK1/2.
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促炎细胞因子 IL-22 通过 STAT3 和 ERK1/2 上调角质形成细胞中角蛋白 17 的表达

DOI:
10.1371/journal.pone.0040797
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Wang G
Wang G
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Zhang W;Dang E;Shi X;Jin L;Feng Z;Hu L;Wu Y;Wang G

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研究促炎细胞因子IL-22对角质形成细胞中K17表达的调节及其在银屑病“K17/T细胞/细胞因子自身免疫环”中的重要作用。通过实时定量PCR、ELISA、Western blot和免疫荧光检测IL-22处理的角质形成细胞中K17的表达。此外,还利用相关抑制剂和siRNA研究了参与K17调控的信号通路。此外,在注射IL-22的小鼠皮肤的表皮中检查K17表达。IL-22诱导的K17表达在角质形成细胞和IL-22注射小鼠皮肤的表皮中在mRNA和蛋白质水平上得到证实,这是对自身免疫环的重要补充。我们进一步研究了其调控机制,发现STAT 3和ERK 1/2都参与了IL-22诱导的K17表达上调。IL-22通过STAT 3和ERK 1/2依赖性机制以剂量依赖性方式上调角质形成细胞中K17的表达。这些结果表明,IL-22也参与了K17/T细胞/细胞因子自身免疫环路,并可能在银屑病的进展中发挥重要作用。
To investigate the regulation of K17 expression by the pro-inflammatory cytokine IL-22 in keratinocytes and its important role in our previously hypothesized “K17/T cell/cytokine autoimmune loop” in psoriasis. K17 expression was examined in the IL-22-treated keratinocytes by real-time quantitative PCR, ELISA, Western blot and Immunofluorescence. In addition, the signaling pathways involved in K17 regulation were investigated with related inhibitors and siRNAs. In addition, K17 expression was examined in the epidermis of IL-22-injected mouse skin. IL-22-induced K17 expression was confirmed in keratinocytes and the epidermis of IL-22-injected mouse skin at both mRNA and protein levels, which is an important complement to the autoimmune loop. We further investigated the regulatory mechanisms and found that both STAT3 and ERK1/2 were involved in the up-regulation of K17 expression induced by IL-22. IL-22 up-regulates K17 expression in keratinocytes in a dose-dependent manner through STAT3- and ERK1/2-dependent mechanisms. These findings indicated that IL-22 was also involved in the K17/T cell/cytokine autoimmune loop and may play an important role in the progression of psoriasis.
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改变的角蛋白 17 肽配体可抑制从银屑病患者分离的角质形成细胞和 T 细胞的体外增殖。
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