Interferon-γ, a strong suppressor of cell proliferation, induces upregulation of keratin K6, one of the inflammatory- and proliferation-associated keratins
Interferon-γ, a strong suppressor of cell proliferation, induces upregulation of keratin K6, one of the inflammatory- and proliferation-associated keratins
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DOI：
10.1046/j.1523-1747.2002.01843.x
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发表时间：
2002-08-01
影响因子：
6.5
通讯作者：
Tamaki, K
中科院分区：
文献类型：
--
作者：
Hattori, N;Komine, M;Tamaki, K
角蛋白K6被称为炎性和过度增殖性角蛋白，并且由炎性和过度增殖剂诱导。在这项研究中，我们证明，干扰素-γ，抗增殖剂，也诱导角蛋白K6。我们使用正常人离体皮肤，正常人培养的角质形成细胞，HaCaT角质形成细胞，和DJM细胞来检查K6的诱导干扰素-γ，免疫组织化学染色，Western印迹分析，启动子氯霉素乙酰转移酶测定，和逆转录酶聚合酶链反应的mRNA。我们成功地证明了干扰素-γ在离体人皮肤和HaCaT角质形成细胞中在蛋白质和信息水平上，以及在培养的正常人角质形成细胞中在启动子水平上诱导角蛋白K6。通过显性负转移基因抑制信号转导转录激活因子1途径，导致干扰素γ抑制K6诱导，并且使用反义寡核苷酸阻断核因子κ B也抑制K6诱导。我们还通过中和抗体阻断了干扰素-γ刺激后角质形成细胞释放的白细胞介素-1 α，这表明K6诱导减少。我们的研究结果表明，少量的白细胞介素-1 α，它不能诱导K6本身，分泌后的刺激，干扰素-γ，并通过干扰素-γ/信号转导转录激活因子1和白细胞介素-1 α/核因子κ B途径的协同效应发生K6的诱导。这是第一份报告，以描述K6诱导表皮角质形成细胞的干扰素-γ，并指出一个可能的信号转导途径，并表明，K6是一个可能的合作伙伴K17在炎症过程中。
Keratin K6 is known as an inflammatory and hyperproliferative keratin, and is induced by an inflammatory and hyperproliferative agent. In this study, we demonstrated that interferon-gamma, an antiproliferative agent, also induces keratin K6. We used normal human ex vivo skin, normal human cultured keratinocytes, HaCaT keratinocytes, and DJM cells to examine the induction of K6 by interferon-gamma, by immunohistochemical staining, Western blot analysis, promoter chloramphenicol acetyl transferase assay, and reverse transcriptase polymerase chain reaction of mRNA. We succeeded in demonstrating the induction of keratin K6 by interferon-gamma in ex vivo human skin and HaCaT keratinocytes at the protein and message level, and in cultured normal human keratinocytes at the promoter level. The inhibition of the signal transducing activator of transcription 1 pathway by a dominant-negative transfer gene caused the inhibition of K6 induction by interferon-gamma, and the blocking of nuclear factor kappaB using antisense oligonucleotides also inhibited the K6 induction. We also blocked the released interleukin-1alpha from keratinocytes after stimulation with interferon-gamma by neutralizing antibodies, which showed a decrease in the K6 induction. Our results suggest that a small amount of interleukin-1alpha, which cannot induce K6 by itself, is secreted upon stimulation by interferon-gamma, and that the induction of K6 occurs through the synergistic effect of the interferon-gamma/signal transducing activator of transcription 1 and interleukin-1alpha/nuclear factor kappaB pathways. This is the first report to describe K6 induction in epidermal keratinocytes by interferon-gamma and indicate a probable signal transduction pathway, and demonstrates that K6 is a possible partner of K17 in the inflammatory process.