DISEASE-ACTIVATED TRANSCRIPTION FACTOR - ALLERGIC REACTIONS IN HUMAN SKIN CAUSE NUCLEAR TRANSLOCATION OF STAT-91 AND INDUCE SYNTHESIS OF KERATIN K17
DISEASE-ACTIVATED TRANSCRIPTION FACTOR - ALLERGIC REACTIONS IN HUMAN SKIN CAUSE NUCLEAR TRANSLOCATION OF STAT-91 AND INDUCE SYNTHESIS OF KERATIN K17
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DOI：
10.1128/mcb.14.7.4759
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发表时间：
1994-07-01
影响因子：
5.3
通讯作者：
BLUMENBERG, M
中科院分区：
文献类型：
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作者：
JIANG, CK;FLANAGAN, S;BLUMENBERG, M
表皮角质形成细胞具有重要的免疫功能，这在伤口愈合、牛皮癣、过敏和炎症反应中都很明显。在这些过程中，角质形成细胞不仅产生吸引和影响淋巴细胞的细胞因子和生长因子，而且还对淋巴细胞产生的多肽因子作出反应。γ干扰素（IFN-I）就是这样一种信号多肽。其主要的分子效应是激活调控靶细胞基因表达的特定转录因子。在这项工作中，我们提出了表皮中淋巴细胞-角质形成细胞信号传导的分子机制。我们已经诱导皮肤延迟型超敏反应，与淋巴细胞的积累有关。这些导致体内角质形成细胞中ifn - γ激活的转录因子STAT-91的激活和核易位，并随后诱导角蛋白K17的转录。在K17角蛋白基因的启动子中，我们已经确定并表征了一个位点，该位点赋予对ifn - γ的响应性，并结合转录因子STAT-91。其他测试的角蛋白基因启动子不受ifn - γ诱导。这些结果在分子水平上表征了由皮肤淋巴细胞浸润产生的信号通路，并导致角化细胞基因表达的特异性改变。
Epidermal keratinocytes have important immunologic functions, which is apparent during wound healing, in psoriasis, and in allergic and inflammatory reactions. In these processes, keratinocytes not only produce cytokines and growth factors that attract and affect lymphocytes but also respond to the polypeptide factors produced by the lymphocytes. Gamma interferon (IFN-I) is one such signaling polypeptide. Its primary molecular effect is activation of specific transcription factors that regulate gene expression in target cells. In this work, we present a molecular mechanism of lymphocyte-keratinocyte signaling in the epidermis. We have induced cutaneous delayed-type hypersensitivity reactions that are associated with an accumulation of lymphocytes. These resulted in activation and nuclear translocation of STAT-91, the IFN-gamma-activated transcription factor, in keratinocytes in vivo and subsequent induction of transcription of keratin K17. Within the promoter of the K17 keratin gene, we have identified and characterized a site that confers the responsiveness to IFN-gamma and that binds the transcription factor STAT-91. Other keratin gene promoters tested were not induced by IFN-gamma. These results characterize at the molecular level a signaling pathway produced by the infiltration of lymphocytes in skin and resulting in the specific alteration of gene expression in keratinocytes.