Ligand-specific and non-specific in vivo modulation of human epidermal cellular retinoic acid binding protein (CRABP).
Retinoic acid (RA) is bound intracellularly by a specific, low molecular weight protein (CRABP), that is unrelated to its nuclear receptor and whose function and regulation are still unknown. In the present study we were able to obtain an in vivo modulation of CRABP by different stimuli in one of the major target organs of RA: the human skin. We found increased CRABP after daily application during 4 days of natural or synthetic retinoids (RA, acitretin, isotretinoin, Ro137410, retinol), that have either a high affinity to CRABP or can be transformed into RA. Only Ro150778 with no affinity and no reported transformation had no effect. No macro- or microscopical changes could be observed with any of the tested compounds. Induction of inflammatory and hyperproliferative changes in the skin by topical dithranol treatment, UVB irradiation or scotch tape stripping also induced a significant increase of CRABP 3 days after exposure. Topical diflucortolone showed not only a tendancy to decrease intrinsic CRABP levels, but significantly reduced the retinoid stimulated rise of CRABP. Thus we conclude that the increase of CRABP in a fully differentiated adult tissue seems to be a biological phenomenon following processes of inflammation and proliferation with a lag of several days, while retinoids seem to be able to induce such a rise independently of, or before, the appearance of such processes. Corticosteroids seem to be inhibitors of this reaction. We discuss the hypothesis that CRABP might function as an intracellular 'buffer' in the case of RA overload.
Hirschel-Scholz
S
S
Clinique de Dermatologie, Hôpital Cantonal Universitaire, Genève, Switzerland.
Siegenthaler
G
G
Saurat
J H
JH
D017255:Acitretin; D000293:Adolescent; D000328:Adult; D000875:Anthralin / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism* / Q000528:radiation effects; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018168:Receptors, Retinoic Acid; D012176:Retinoids / Q000494:pharmacology; D013256:Steroids / Q000494:pharmacology; D014212:Tretinoin / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D014466:Ultraviolet Rays; D014801:Vitamin A / Q000378:metabolism
D002352:Carrier Proteins; D018168:Receptors, Retinoic Acid; D012176:Retinoids; D013256:Steroids; D014801:Vitamin A; D014212:Tretinoin; D017255:Acitretin; D000875:Anthralin