Histidase expression in human epidermal keratinocytes: Regulation by differentiation status and all-trans retinoic acid

• Published in: Journal of dermatological science 2008-06, Vol.50 (3), p.209-215
• Main Authors: Eckhart, Leopold, Schmidt, Martina, Mildner, Michael, Mlitz, Veronika, Abtin, Arby, Ballaun, Claudia, Fischer, Heinz, Mrass, Paul, Tschachler, Erwin
• Format: Article
• Language: English
• Subjects: Cell Differentiation - drug effects; Cell Differentiation - physiology; Cells, Cultured; Dermatology; Epidermis - cytology; Epidermis - enzymology; Gene Expression Regulation, Enzymologic - drug effects; Gene Expression Regulation, Enzymologic - physiology; Gene Expression Regulation, Enzymologic - radiation effects; Histidase; Histidine Ammonia-Lyase - genetics; Histidine Ammonia-Lyase - metabolism; Humans; Keratinocyte differentiation; Keratinocytes - cytology; Keratinocytes - drug effects; Keratinocytes - enzymology; Keratolytic Agents - pharmacology; Retinoic acid; Transcription, Genetic - drug effects; Transcription, Genetic - physiology; Transcription, Genetic - radiation effects; Tretinoin - pharmacology; Ultraviolet irradiation; Ultraviolet Rays; Up-Regulation - drug effects; Up-Regulation - physiology; Up-Regulation - radiation effects; Urocanic acid
• ISSN: 0923-1811; 1873-569X
• DOI: 10.1016/j.jdermsci.2007.12.009

Summary Background 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. Objective We have investigated the transcriptional regulation of histidase expression in epidermal keratinocytes. Methods Human epidermal keratinocytes were cultured in vitro and exposed to UV irradiation, a number of cytokines and all-trans retinoic acid (ATRA) (1 μM). 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. Results 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. Conclusions 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.