Slominski A T, Roloff B, Zbytek B, Wei E T, Fechner K, Curry J, Wortsman J
Department of Pathology, Medical Center, Loyola University, Maywood, Illinois 60153, USA.
In Vitro Cell Dev Biol Anim. 2000 Mar;36(3):211-6. doi: 10.1290/1071-2690(2000)036<0211:CRHARP>2.0.CO;2.
Following previous findings in human skin of the functional expression of genes for the corticotropin releasing hormone (CRH) receptor type 1 (CRH-R1) and CRH itself, we searched for local phenotypic effects for peptides related to CRH. We now report that CRH, sauvagine, and urocortin inhibit proliferation of human HaCaT keratinocytes in a dose-dependent manner. The peptides produced variable cyclic adenosine 3':5'-monophosphate stimulation, with CRH having the highest potency. Binding of iodine 125 CRH to intact keratinocytes was inhibited by increasing doses of CRH, sauvagine, or urocortin, all showing equal inhibitory potency. Immunocytochemistry identified CRH-R1 immunoreactivity in HaCaT keratinocytes. In conclusion, CRH (exogenous or produced locally) and the related urocortin and sauvagine peptides can modify human keratinocyte phenotype through a receptor-mediated pathway.
根据先前在人类皮肤中发现的促肾上腺皮质激素释放激素(CRH)1型受体(CRH-R1)和CRH本身基因的功能表达,我们寻找了与CRH相关肽的局部表型效应。我们现在报告,CRH、蛙皮素和尿皮质素以剂量依赖的方式抑制人HaCaT角质形成细胞的增殖。这些肽产生了不同程度的环磷酸腺苷刺激,其中CRH的效力最高。随着CRH、蛙皮素或尿皮质素剂量的增加,125碘CRH与完整角质形成细胞的结合受到抑制,三者均显示出同等的抑制效力。免疫细胞化学鉴定出HaCaT角质形成细胞中有CRH-R1免疫反应性。总之,CRH(外源性或局部产生)以及相关的尿皮质素和蛙皮素肽可通过受体介导的途径改变人类角质形成细胞表型。