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Cyclosporine in Psoriasis TreatmentInhibition of Keratinocyte Cell-Cycle Progression in G1 Independent of Effects on Transforming Growth Factor /Epidermal Growth Factor Receptor Pathways
Lakshmi Khandke, PhD;
Jeffrey F. Krane, MS;
Robin Ashinoff, MD;
Lisa Staiano-Coico, PhD;
Angela Granelli-Piperno, PhD;
Andrew D. Luster, MD, PhD;
D. Martin Carter, MD, PhD;
James G. Krueger, MD, PhD;
Alice B. Gottlieb, MD, PhD
Arch Dermatol. 1991;127(8):1172-1179.
Abstract
Cyclosporine, an immunosuppressive drug, is effective in the treatment of recalcitrant psoriasis. Previous work suggested that keratinocyte hyperproliferation and inflammation are linked in psoriasis and that immune mechanisms participate in the pathogenesis of psoriasis. Transforming growth factor (TGF) may be an important regulatory factor of epidermal growth as overproduction of TGF- is associated with epidermal hyperplasia in psoriatic plaques and epidermal growth factor receptors are overexpressed in psoriatic epithelium. In this study, the effects of cyclosporine on cultured human keratinocytes were examined. Cyclosporine specifically inhibited keratinocyte cell-cycle progression in the G1 phase without causing keratinocytes to terminally differentiate. Cyclosporine did not decrease the expression of TGF- or epidermal growth factor receptors. These results suggest that the effects of cyclosporine on psoriatic skin are unrelated to direct effects on autocrine growth regulation of keratinocytes via TGF- production or of epidermal growth factor receptor modulation.
(Arch Dermatol. 1991;127:1172-1179)
Author Affiliations
From the Laboratory for Investigative Dermatology (Drs Khandke, Ashinoff, Carter, Krueger, and Gottlieb, and Mr Krane), the Laboratory for Cellular Immunology and Physiology (Drs Granelli-Piperno and Luster), Rockefeller University, and the Department of Surgery (Dr Staiano-Coico), The Cornell University Medical College, New York, NY.
Footnotes
Accepted for publication March 27, 1991.
Reprint requests to Laboratory for Investigative Dermatology, Rockefeller University, 1230 York Ave, New York, NY 10021 (Dr Gottlieb).
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