Bessis D, Molès J P, Basset-Séguin N, Tesniere A, Arpin C, Guilhou J J
Laboratoire de Dermatologie Moléculaire, Université Montpellier, Institut Universitaire de Recherche Clinique, 641 Avenue du Doyen Gaston Giraud, 34093 Montpellier cedex 5, France.
Br J Dermatol. 2004 Oct;151(4):737-45. doi: 10.1111/j.1365-2133.2004.06116.x.
Psoriasis is a common inflammatory skin disease characterized by uncontrolled proliferation of keratinocytes and recruitment of T lymphocytes into the skin. The possible role of human endogenous retroviruses (HERVs) in the induction of psoriasis has been suggested, based upon the previous observations of retrovirus-like particles in psoriasis from skin lesional plaques, urine and stimulated lymphocytes.
To investigate the expression of HERV-E transmembrane envelope glycoprotein (HERV-E env) in normal, psoriatic and atopic human skin, and to examine the influence of ultraviolet (UV) B irradiation on HERV-E env expression in normal human epidermal keratinocytes.
The analysis was performed on both skin biopsies and organotypic skin cultures using immunofluorescence and Western immunoblotting. UVB irradiation (312 nm) of cultured normal human keratinocytes was performed using a dose of 30 mJ cm(-2).
Positive staining was observed in most of the psoriatic and atopic skin samples, whereas only 15% of the normal skin samples were faintly positive. In addition, the pattern of expression of HERV-E env differed markedly in psoriasis vs. atopy. By Western blotting analysis, two main proteins of 54 and 57 kDa were detected in extracts of normal skin, normal keratinocyte cultures and reconstructed epidermis from psoriatic and normal punch biopsies. An increased level of expression of these proteins was noted in extracts from psoriatic vs. normal reconstructed epidermis. The overexpression of the 57-kDa protein in normal human cultured keratinocytes was dramatically reduced by UVB irradiation.
These data suggest for the first time that HERV-E env is expressed in normal and pathological human skin. Further studies are now required to elucidate the role of such viral proteins in the pathogenesis of psoriasis.
银屑病是一种常见的炎症性皮肤病,其特征为角质形成细胞的不受控制增殖以及T淋巴细胞向皮肤的募集。基于先前在银屑病皮肤病变斑块、尿液和刺激淋巴细胞中观察到的逆转录病毒样颗粒,有人提出人类内源性逆转录病毒(HERVs)在银屑病诱导中可能发挥的作用。
研究HERV-E跨膜包膜糖蛋白(HERV-E env)在正常、银屑病和特应性人类皮肤中的表达,并检测紫外线(UV)B照射对正常人表皮角质形成细胞中HERV-E env表达的影响。
使用免疫荧光和蛋白质免疫印迹法对皮肤活检组织和器官型皮肤培养物进行分析。使用30 mJ/cm²的剂量对培养的正常人角质形成细胞进行UVB照射(312 nm)。
在大多数银屑病和特应性皮肤样本中观察到阳性染色,而只有15%的正常皮肤样本呈弱阳性。此外,HERV-E env的表达模式在银屑病和特应性皮炎中明显不同。通过蛋白质免疫印迹分析,在正常皮肤、正常角质形成细胞培养物以及银屑病和正常打孔活检组织的重建表皮提取物中检测到54 kDa和57 kDa的两种主要蛋白质。与正常重建表皮提取物相比,银屑病重建表皮提取物中这些蛋白质的表达水平升高。UVB照射显著降低了正常人培养角质形成细胞中57 kDa蛋白质的过表达。
这些数据首次表明HERV-E env在正常和病理性人类皮肤中表达。现在需要进一步研究以阐明此类病毒蛋白在银屑病发病机制中的作用。