Regulation of the skin immune system by retinoids during carcinogenesis.
One of the immunosuppressive effects of both ultraviolet (UV) light and chemical carcinogens is to deplete Langerhans cells (LC) from the epidermis, suggesting that these cells play an important role in inducing immune responses to developing tumors during the early phases of carcinogenesis. Retinoids such as all-trans-retinoic acid (RA) are natural or synthetic derivatives of vitamin A; RA binds to nuclear receptors in the skin, effecting transcription of a wide range of genes. Topical application of RA prevents the tumor promotor 12-O-tetradecanoylphorbol-13-acetate (TPA) from depleting the density of LC in murine epidermis. In contrast, topical RA did not itself alter the normal LC density. RA also inhibited the development of TPA-induced immunosuppression to a locally applied contact sensitizer. Topical RA also prevented UV light from reducing the density of both LC and Thy-1+ dendritic epidermal cells (Thy-1+ dEC). However, the RA treatment did not prevent local immunosuppression to the contact sensitizer from developing in response to UV irradiation. The reasons for this are unclear, however, it is possible that RA does not inhibit some other immunosuppressive effect of UV light. Temarotene, a recently developed synthetic retinoid also inhibited UV light from reducing the LC and Thy-1+ dEC density from murine epidermis. Thus part of the anti-carcinogenic activity of retinoids may be due to their ability to protect LC during the early stages of carcinogenesis.
Department of Dermatology, University of Sydney, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.
G M
GM
Halliday
K K
KK
Ho
R S
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Barnetson
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D007107:Immune System / Q000187:drug effects; D007801:Langerhans Cells / Q000276:immunology; D008562:Membrane Glycoproteins / Q000032:analysis; D051379:Mice; D012176:Retinoids / Q000494:pharmacology*; D012867:Skin / Q000276:immunology*; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000209:etiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018800:Thy-1 Antigens; D014466:Ultraviolet Rays / Q000009:adverse effects
D000954:Antigens, Surface; D008562:Membrane Glycoproteins; D012176:Retinoids; D018800:Thy-1 Antigens; D013755:Tetradecanoylphorbol Acetate