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皮肤源性抗白细胞蛋白酶(SKALP)和表皮脂肪酸结合蛋白(E-FABP):银屑病表型的两种新型标志物,对局部类固醇有不同反应。

Skin-derived antileukoproteinase (SKALP) and epidermal fatty acid-binding protein (E-FABP): two novel markers of the psoriatic phenotype that respond differentially to topical steroid.

作者信息

Kuijpers A L, Bergers M, Siegenthaler G, Zeeuwen P L, van de Kerkhof P C, Schalkwijk J

机构信息

Department of Dermatology, University Hospital Nijmegen, The Netherlands.

出版信息

Acta Derm Venereol. 1997 Jan;77(1):14-9. doi: 10.2340/0001555577014019.

Abstract

Recently we have described two novel markers for disturbed epidermal differentiation, which are strongly upregulated in psoriatic epidermis: skin-derived antileukoproteinase (SKALP) and epidermal fatty acid-binding protein (E-FABP). No data are available on the kinetics of SKALP and E-FABP expression in vivo and the relation with epidermal growth and differentiation. We used treatment of lesional psoriatic skin with topical steroid as a model to correlate the expression pattern of SKALP and E-FABP with known cell biological events during regression of the psoriatic lesion. Expression of these markers was studied using immunohistochemistry and Northern blot analysis. After 4 weeks of treatment a substantial clinical improvement was induced by the topical steroid, whereas no significant improvement had occurred at the placebo-treated sides. The expression of SKALP following treatment with steroid was nearly undetectable both at the protein and mRNA level. Mitotic activity, as measured by Ki-67 staining, and cytokeratin 16 expression were downregulated to normal levels in the steroid-treated epidermis. In contrast, although there was a marked decrease of E-FABP mRNA, the staining pattern for E-FABP at the protein level was not affected. After 4 weeks of treatment with steroid the complete suprabasal compartment remained positive, even after considerable clinical improvement of the lesion. We conclude that SKALP and cytokeratin 16 are markers that are downregulated even before complete macroscopic clearance of the lesion. The kinetics of E-FABP expression is distinct from the other molecules and lags behind the clinical signs of psoriasis.

摘要

最近,我们描述了两种用于表征表皮分化紊乱的新型标志物,它们在银屑病表皮中强烈上调:皮肤源性抗白细胞蛋白酶(SKALP)和表皮脂肪酸结合蛋白(E-FABP)。目前尚无关于SKALP和E-FABP在体内表达动力学以及与表皮生长和分化关系的数据。我们以局部类固醇治疗银屑病皮损为模型,将SKALP和E-FABP的表达模式与银屑病皮损消退过程中已知的细胞生物学事件相关联。使用免疫组织化学和Northern印迹分析研究这些标志物的表达。治疗4周后,局部类固醇诱导了显著的临床改善,而安慰剂治疗侧未出现显著改善。类固醇治疗后,SKALP在蛋白质和mRNA水平的表达几乎无法检测到。通过Ki-67染色测量的有丝分裂活性和细胞角蛋白16表达在类固醇治疗的表皮中下调至正常水平。相比之下,虽然E-FABP mRNA有明显下降,但E-FABP在蛋白质水平的染色模式未受影响。类固醇治疗4周后,即使皮损有明显的临床改善,整个基底上层仍呈阳性。我们得出结论,SKALP和细胞角蛋白16是在皮损完全宏观清除之前就下调的标志物。E-FABP表达的动力学与其他分子不同,且落后于银屑病的临床症状。

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