Heme oxygenase-1 induction attenuates imiquimod-induced psoriasiform inflammation by negative regulation of Stat3 signaling.
Heme oxygenase-1 induction attenuates imiquimod-induced psoriasiform inflammation by negative regulation of Stat3 signaling.
复制标题
血红素加氧酶 1 诱导通过 Stat3 信号传导的负调节减轻咪喹莫特诱导的银屑病炎症
DOI：
10.1038/srep21132
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发表时间：
2016-02-19
影响因子：
4.6
通讯作者：
Wang H
中科院分区：
文献类型：
--
作者：
Zhang B;Xie S;Su Z;Song S;Xu H;Chen G;Cao W;Yin S;Gao Q;Wang H
血红素氧合酶-1（HO-1）是一种应激诱导蛋白，具有潜在的抗炎作用，在皮肤损伤和伤口愈合中起重要作用。然而，HO-1在皮肤炎性疾病如银屑病中的功能仍然未知。Stat 3是一种已知的诱导炎症和调节细胞分化的转录因子，其异常激活直接参与银屑病的发病和发展。因此，靶向Stat 3在银屑病的治疗中是潜在有益的。在这项研究中，HO-1的激活显着减轻了疾病相关的发病机制异常。为了确定HO-1对Th 17相关细胞因子发挥免疫保护作用的机制，IL 6/IL 22诱导的Stat 3激活被显着抑制，同时伴有细胞增殖下降并逆转异常细胞增殖。重要的是，HO-1诱导的Stat 3抑制是通过激活蛋白酪氨酸磷酸酶SHP-1介导的。总的来说，我们的研究提供了直接的证据表明HO-1可能是银屑病的一个有用的治疗靶点。HO-1激活后SHP-1介导的Stat 3激活抑制是调节Stat 3激活的独特分子机制。
Heme oxygenase-1 (HO-1), a stress-inducible protein with a potential anti-inflammatory effect, plays an important role in skin injury and wound healing. However, the function of HO-1 in cutaneous inflammatory diseases, such as psoriasis, remains unknown. The abnormal activation of Stat3, a known transcription factor that induces inflammation and regulates cell differentiation, is directly involved in the pathogenesis and development of psoriasis. Hence, targeting Stat3 is potentially beneficial in the treatment of psoriasis. In this study, HO-1 activation significantly alleviated the disease-related pathogenesis abnormality. To determine the mechanism by which HO-1 exerts immune protection on Th17-related cytokines, IL6/IL22-induced Stat3 activation was significantly suppressed, accompanied by decreased cell proliferation and reversed abnormal cell proliferation. Importantly, HO-1-induced Stat3 suppression was mediated through the activation of protein tyrosine phosphatase SHP-1. Overall, our study provides direct evidence indicating that HO-1 might be a useful therapeutic target for psoriasis. SHP-1-mediated suppression of Stat3 activation after HO-1 activation is a unique molecular mechanism for the regulation of Stat3 activation.