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Research Article| Volume 50, ISSUE 3, P209-215, June 2008

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

  • Author Footnotes
    1 These authors contributed equally to this work.
    Leopold Eckhart
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Department of Dermatology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria
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  • Author Footnotes
    1 These authors contributed equally to this work.
    Martina Schmidt
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Department of Dermatology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria
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  • Michael Mildner
    Affiliations
    Department of Dermatology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria
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  • Veronika Mlitz
    Affiliations
    Department of Dermatology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria
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  • Arby Abtin
    Affiliations
    Department of Dermatology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria
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  • Claudia Ballaun
    Affiliations
    Department of Dermatology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria
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  • Heinz Fischer
    Affiliations
    Department of Dermatology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria
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  • Author Footnotes
    2 Present address: Immunology Program, The Wistar Institute, Philadelphia, PA 19104, United States.
    Paul Mrass
    Footnotes
    2 Present address: Immunology Program, The Wistar Institute, Philadelphia, PA 19104, United States.
    Affiliations
    Department of Dermatology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria
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  • Erwin Tschachler
    Correspondence
    Corresponding author at: Department of Dermatology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria. Tel.: +43 1 4081271; fax: +43 1 4034922.
    Affiliations
    Department of Dermatology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria

    Centre de Recherches et d’ Investigations Epidermiques et Sensorielles (CE.R.I.E.S.), Neuilly 92521, France
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  • Author Footnotes
    1 These authors contributed equally to this work.
    2 Present address: Immunology Program, The Wistar Institute, Philadelphia, PA 19104, United States.

      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.

      Keywords

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