Eckhart Leopold, Schmidt Martina, Mildner Michael, Mlitz Veronika, Abtin Arby, Ballaun Claudia, Fischer Heinz, Mrass Paul, Tschachler Erwin
Department of Dermatology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
J Dermatol Sci. 2008 Jun;50(3):209-15. doi: 10.1016/j.jdermsci.2007.12.009. Epub 2008 Feb 15.
Histidase (histidine ammonia lyase) converts histidine into urocanic acid, the main ultraviolet (UV) light absorption factor of the stratum corneum. It is unknown if and how histidase is regulated in the epidermis.
We have investigated the transcriptional regulation of histidase expression in epidermal keratinocytes.
Human epidermal keratinocytes were cultured in vitro and exposed to UV irradiation, a number of cytokines and all-trans retinoic acid (ATRA) (1 microM). Keratinocyte differentiation was triggered by maintaining confluent cells in monolayer culture and by establishing three-dimensional skin equivalents. The mRNA expression level of histidase in keratinoytes as well as in the epidermis and other tissues was determined by quantitative real-time PCR. Protein expression was determined by Western blot analysis.
Human epidermis contained higher levels of histidase transcripts than all other tissues investigated. Expression of histidase strongly increased at the mRNA and protein levels during differentiation of primary keratinocytes in vitro. Treatment of keratinocytes with UVA and UVB did not significantly change the expression level of histidase. By contrast, ATRA suppressed histidase expression almost completely.
Our results show that histidase is upregulated during keratinocyte differentiation and that ATRA but not UV irradiation modulates the expression level of histidase. Suppression of histidase-mediated production of urocanic acid may contribute to the increase in UV sensitivity that is caused by treatment with retinoids.
组氨酸酶（组氨酸解氨酶）将组氨酸转化为尿刊酸，尿刊酸是角质层主要的紫外线吸收因子。目前尚不清楚组氨酸酶在表皮中是否以及如何受到调控。
我们研究了表皮角质形成细胞中组氨酸酶表达的转录调控。
体外培养人表皮角质形成细胞，并使其暴露于紫外线照射、多种细胞因子及全反式维甲酸（ATRA，1微摩尔）。通过将汇合的细胞维持在单层培养以及构建三维皮肤等效物来诱导角质形成细胞分化。采用定量实时聚合酶链反应测定角质形成细胞以及表皮和其他组织中组氨酸酶的信使核糖核酸表达水平。通过蛋白质印迹分析测定蛋白质表达。
人表皮中组氨酸酶转录本水平高于所研究的所有其他组织。在原代角质形成细胞体外分化过程中，组氨酸酶的表达在信使核糖核酸和蛋白质水平均显著增加。用UVA和UVB处理角质形成细胞并未显著改变组氨酸酶的表达水平。相比之下，ATRA几乎完全抑制了组氨酸酶的表达。
我们的结果表明，组氨酸酶在角质形成细胞分化过程中上调，并且ATRA而非紫外线照射调节组氨酸酶的表达水平。抑制组氨酸酶介导的尿刊酸生成可能有助于解释维甲酸治疗所导致的紫外线敏感性增加。
