Cyclosporine in psoriasis treatment. Inhibition of keratinocyte cell-cycle progression in G1 independent of effects on transforming growth factor alpha/epidermal growth factor receptor pathways.
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) alpha may be an important regulatory factor of epidermal growth as overproduction of TGF-alpha 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-alpha 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-alpha production or of epidermal growth factor receptor modulation.
Laboratory for Investigative Dermatology, Rockefeller University, New York, NY 10021.
L
L
Khandke
J F
JF
Krane
R
R
Ashinoff
L
L
Staiano-Coico
A
A
Granelli-Piperno
A D
AD
Luster
D M
DM
Carter
J G
JG
Krueger
A B
AB
Gottlieb
D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D003524:Cyclosporins / Q000494:pharmacology* / Q000627:therapeutic use; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D066246:ErbB Receptors / Q000096:biosynthesis* / Q000187:drug effects; D016193:G1 Phase / Q000187:drug effects*; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011565:Psoriasis / Q000188:drug therapy; D014158:Transcription, Genetic / Q000187:drug effects; D016211:Transforming Growth Factor alpha / Q000096:biosynthesis* / Q000187:drug effects; D011503:Transglutaminases / Q000378:metabolism
D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D003524:Cyclosporins; D016207:Cytokines; D016211:Transforming Growth Factor alpha; D011503:Transglutaminases; D066246:ErbB Receptors