Chen S H, Arany I, Apisarnthanarax N, Rajaraman S, Tyring S K, Horikoshi T, Brysk H, Brysk M M
Department of Dermatology, University of Texas Medical Branch, Galveston, Texas 77555, USA.
FASEB J. 2000 Mar;14(3):565-71. doi: 10.1096/fasebj.14.3.565.
Psoriasis is a T cell-mediated inflammatory disease characterized by hyperproliferation and by aberrant differentiation. We found cathepsin D and zinc-alpha(2)-glycoprotein, two catalytic enzymes associated with apoptosis and desquamation, to be present in the stratum corneum of the normal epidermis but absent from the psoriatic plaque. Psoriasis is characterized by an altered response to interferon-gamma (IFN-gamma), including the induction of apoptosis in normal but not in psoriatic keratinocytes, often with opposite effects on gene expression of suprabasal proteins. We found that IFN-gamma binding and signaling were attenuated in psoriasis: The IFN-gamma receptor, the signal transducer and activator of transcription STAT-1, and the interferon regulatory factor IRF-1 were strongly up-regulated by IFN-gamma in normal keratinocytes, but not in psoriatic ones. IFN-gamma strongly up-regulated the expression of the catalytic enzymes cathepsin D and zinc-alpha(2)-glycoprotein in normal keratinocytes but down-regulated them in psoriatic ones; the reverse was true of the apoptotic suppressor bcl-2. We believe that the aberrant response to IFN-gamma plays a central role in the pathophysiology of psoriasis, particularly the disruption of apoptosis and desquamation.
银屑病是一种由T细胞介导的炎症性疾病，其特征为过度增殖和异常分化。我们发现组织蛋白酶D和锌-α(2)-糖蛋白这两种与细胞凋亡和脱屑相关的催化酶存在于正常表皮的角质层中，但在银屑病斑块中却不存在。银屑病的特征是对γ干扰素（IFN-γ）的反应发生改变，包括在正常角质形成细胞中诱导细胞凋亡，而在银屑病角质形成细胞中则不然，这通常对基底上层蛋白的基因表达产生相反的影响。我们发现银屑病中IFN-γ的结合和信号传导减弱：在正常角质形成细胞中，IFN-γ可强烈上调IFN-γ受体、信号转导和转录激活因子STAT-1以及干扰素调节因子IRF-1的表达，但在银屑病角质形成细胞中则不然。IFN-γ在正常角质形成细胞中强烈上调组织蛋白酶D和锌-α(2)-糖蛋白这两种催化酶的表达，但在银屑病角质形成细胞中则下调；凋亡抑制因子bcl-2的情况则相反。我们认为，对IFN-γ的异常反应在银屑病的病理生理学中起着核心作用，尤其是在细胞凋亡和脱屑的破坏方面。
