Increased expression of epidermal IL-8 receptor in psoriasis. Down-regulation by FK-506 in vitro.
Increased expression of epidermal IL-8 receptor in psoriasis. Down-regulation by FK-506 in vitro.
复制标题
牛皮癣中表皮 IL-8 受体的表达增加。
作者：
Barbara S. Schulz;G. Michel;S. Wagner;R. Süss;A. Beetz;R. Peter;L. Kemény;T. Ruzicka
IL-8是一种具有促炎和促生长活性的趋化细胞因子。最近，它已被证明影响角质形成细胞的几个功能，包括HLA-DR表达，趋化性，并通过结合到一个特定的受体增殖。由于寻常型银屑病的特点是表皮过度增殖和炎性细胞浸润，我们研究了IL-8及其受体的表达在正常和银屑病表皮半定量逆转录-聚合酶链反应。此外，原癌基因c-ras、c-raf、c-myc和HER-2的mRNA水平也被研究作为银屑病表皮中潜在的生长促进刺激。IL-8 mRNA仅在银屑病皮损中表达，而IL-8 R特异性mRNA在银屑病皮损中表达增加10倍。原癌基因mRNA水平无显著差异。为了检测银屑病表皮中大量增加的IL-8 R水平的相关性，我们研究了抗银屑病药物FK-506对特异性IL-8和IL-8 R mRNA表达的影响。FK-506剂量依赖性地抑制IL-8 R表达和功能。我们的数据表明，在银屑病皮肤中，升高的IL-8水平和显著增加的IL-8 R表达可能共同诱导银屑病的主要体征-表皮过度增殖和白细胞浸润。IL-8 R可能被证明是FK-506等抗银屑病药物的分子靶点。
IL-8 is a chemotactic cytokine with proinflammatory and growth-promoting activities. Recently it has been shown to influence several functions of keratinocytes, including HLA-DR expression, chemotaxis, and proliferation by binding to a specific receptor. Because psoriasis vulgaris is characterized by epidermal hyperproliferation and infiltration of inflammatory cells, we investigated the expression of IL-8 and its receptor in normal and psoriatic epidermis using semiquantitative reverse-transcriptase-polymerase chain reaction. In addition the mRNA levels of the proto-oncogenes c-ras, c-raf, c-myc, and HER-2 were also investigated as potential growth-promoting stimuli in psoriatic epidermis. IL-8 mRNA was only detected in lesional psoriatic epidermis, and IL-8R-specific mRNA was found to be 10 times increased in lesional psoriatic epidermis. There was no significant difference in the protooncogene mRNA levels. In order to test the relevance of the massively increased IL-8R levels in psoriatic epidermis, we investigated the effect of the antipsoriatic drug FK-506 on specific IL-8 and IL-8R mRNA expression. FK-506 dose dependently inhibited IL-8R expression and function. Our data suggest that in psoriatic skin, elevated IL-8 levels and markedly increased IL-8R expression may act in concert to induce the cardinal signs of psoriasis--epidermal hyperproliferation and leukocyte infiltration. IL-8R may prove a molecular target for antipsoriatic drugs such as FK-506.