Psoriatic keratinocytes show reduced IRF-1 and STAT-1α activation in response to γ-IFN
Psoriatic keratinocytes show reduced IRF-1 and STAT-1α activation in response to γ-IFN
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DOI：
10.1096/fasebj.13.3.495
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发表时间：
1999-03-01
期刊：
影响因子：
4.8
通讯作者：
McKenzie, RC
中科院分区：
文献类型：
--
作者：
Jackson, M;Howie, SEM;McKenzie, RC
银屑病是一种以角质形成细胞(MC)过度增殖为特征的慢性炎症性皮肤病，皮损中有T细胞浸润，分泌γ-干扰素(γ-干扰素)被认为是维持银屑病表型所必需的。在正常皮肤中，γ-干扰素是一种强有力的增殖抑制因子，但尽管有伽马-LFN的存在，银屑病斑块中KC的增殖仍持续存在。干扰素调节因子-1(IRF-1)免疫组织化学染色显示，IRF-1定位于正常和非皮损银屑病皮肤的表皮基底细胞，而在银屑病皮损中，IRF-1定位于基底层或完全缺失。这一发现导致了一种假设，即银屑病KC可能存在伽马-干扰素途径中的异常信号。为了验证这一假设，我们检测了γ-干扰素刺激后银屑病KC中IRF-1和信号转导及转录激活子(STAT)-1α转录因子的激活，并用伽玛-干扰素刺激原代培养的正常人和非皮损皮肤的KC，随后用凝胶迁移率改变分析检测转录因子的激活。银屑病患者KC在伽玛-干扰素刺激后IRF-1和STAT-1α的诱导激活明显减少，与正常KC相比，干扰素诱导的IRF-1和STAT活性降低，提示银屑病KC在缺乏其他细胞类型影响的情况下，其生长和分化调控存在根本性缺陷。
Psoriasis is a chronic inflammatory dermatosis characterized by hyperproliferative keratinocytes (MC), The skin lesions are infiltrated by T cells, which secrete gamma interferon (gamma-IFN) and are believed to be necessary to maintain the psoriatic phenotype, In normal KC, gamma-IFN is a potent inhibitor of proliferation, but proliferation of KC persists in psoriatic plaques despite the presence of gamma-lFN, Immunostaining of interferon regulatory factor-1 (IRF-1) revealed that IRF-1 was localized to the basal cells of the epidermis in normal and in nonlesional psoriatic skin, but was suprabasal or completely absent in lesional psoriatic skin. This finding led to the hypothesis that abnormal signaling in the gamma-IFN pathway may occur in psoriatic KC. To test this hypothesis, we measured activation of IRF-1 and signal transducer and activator of transcription (STAT)-1 alpha transcription factors in KC after stimulation with gamma-IFN, Primary cultures of KC from normal and nonlesional psoriatic skin were stimulated with gamma-IFN and subsequent transcription factor activation was measured by electrophoretic mobility shift assay, Psoriatic KC showed a reduced induction of IRF-1 and STAT-1 alpha activation after stimulation with gamma-IFN, compared with normal KC, Reduced activation of IRF-1 and STAT-lar in response to gamma-IFN indicates a fundamental defect in the growth and differentiation control of psoriatic KC in the absence of the influence of other cell types.