Nonimmunosuppressive ciclosporin H inhibits the growth and DNA synthesis of cultured normal human epidermal keratinocytes.
Ciclosporin H (CsH) is an epimer (11-D-N-methyl-L-valine) of ciclosporin A (CsA) devoid of immunosuppressive properties. The known antiproliferative effect of CsA on epidermal keratinocytes (EK) grown in vitro prompted us to study the effect of CsH (at the doses of 0.5, 1, 3.5 and 5 micrograms/ml) on the growth and DNA synthesis (5-bromo-2'-deoxyuridine incorporation). CsH was observed to reduce both the number and DNA synthesis of EK in a statistically significant manner at the dosage of 5 micrograms/ml after 24, 48 and 72 h in culture. These results show that the immunosuppressive properties of the ciclosporins (Cs) are dissociated from the antiproliferative ones on EK and highlight the interest of further in vivo studies that may lead to therapeutic applications of Cs in hyperproliferative epidermal diseases requiring no immunosuppression.
Ramirez-Bosca
A
A
INSERM U209, CNRS DO 601, Department of Dermatology, Edouard Herriot Hospital, Lyon, France.
Kanitakis
J
J
Haftek
M
M
Faure
M
M
Castells-Rodellas
A
A
Thivolet
J
J
D001973:Bromodeoxyuridine / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D016572:Cyclosporine; D003524:Cyclosporins / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis*; D003864:Depression, Chemical; D006801:Humans; D066298:In Vitro Techniques; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism*; D012867:Skin / Q000166:cytology
D003524:Cyclosporins; D016572:Cyclosporine; D004247:DNA; C050025:cyclosporin H; D001973:Bromodeoxyuridine