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Topical all-trans retinoic acid (RA) induces an early, coordinated increase in RA-inducible skin-specific gene/psoriasin and cellular RA-binding protein II mRNA levels which precedes skin erythema

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Abstract

Separation of specific and nonspecific “irritant” effects of topical all-trans retinoic acid (RA) is a key to understanding the mechanism of retinoid action in skin. Cellular RA-binding protein (CRABP) II has been found to be a marker of RA activity in human skin. We have also previously identified a skin-specific gene (RIS-1/psoriasin) which is rapidly induced in human skin treated with RA. Here we compared the kinetics and time-course of RIS-1 and CRABP II gene activation by RA, sodium lauryl sulfate (SLS), a classical irritant, and their vehicle (VH), using a quantitative reverse transcription polymerase chain reaction. RIS-1 and CRABP II were both expressed at very low levels in untreated normal human skin, and in RA-treated skin the kinetics and time course of RIS-1 and CRABP II mRNA induction were similar. Relative to VH-treated skin, RA induced RIS-1 mRNA levels within 6 h, which further increased to 6.4-fold by 24 h (n=4). Similarly, CRABP II mRNA levels increased from 2.6-fold at 6 h to 7.8-fold after 24 h. At 48 h the relative mRNA levels for both genes decreased towards the steady-state levels. Relative to SLS-treated skin, RIS-1 mRNA increased by 3.2-fold after 6 h and by 5.1-fold after 12 h (n=3). Also, a 2.6-fold higher CRABP II mRNA observed after 6 h increased to 6-fold after 12 h. After 24 and 48 h RA treatment the relative mRNA levels for both genes decreased towards the steady-state levels. RA-induced skin erythema was not obvious until 24 to 48 h. We conclude, therefore, that induction of RIS-1 and CRABP II mRNA levels by topical RA in human skin are early, coordinated molecular events which precede the clinical cutaneous erythematous response to RA.

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Authors and Affiliations

  1. Department of Dermatology, University Medical Center Benjamin Franklin, The Free University of Berlin, Hindenburgdamm 30, D-12200, Berlin, Germany

    Christos C. Zouboulis & Constantin E. Orfanos

  2. Department of Dermatology, University of Michigan Medical Center, 1910 A. Alfred Taubman Health Care Center, 48109-0314, Ann Arbor, MI, USA

    John J. Voorhees

  3. Skin Clinical Investigations Group, Colgate-Palmolive Company, 909 River Road, 08855-1343, Piscataway, NJ, USA

    Amir Tavakkol

Authors
  1. Christos C. Zouboulis
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  2. John J. Voorhees
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  3. Constantin E. Orfanos
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  4. Amir Tavakkol
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Correspondence to Christos C. Zouboulis.

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Zouboulis, C.C., Voorhees, J.J., Orfanos, C.E. et al. Topical all-trans retinoic acid (RA) induces an early, coordinated increase in RA-inducible skin-specific gene/psoriasin and cellular RA-binding protein II mRNA levels which precedes skin erythema. Arch Dermatol Res 288, 664–669 (1996). https://doi.org/10.1007/BF02505275

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  • DOI: https://doi.org/10.1007/BF02505275

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