Cyclosporin a promotes hair epithelial cell proliferation and modulates protein kinase C expression and translocation in hair epithelial cells.
Cyclosporin A is an immunosuppressive agent known to cause hirsutism. The mechanisms of action that cause hirsutism have not been fully elucidated, however. We have previously reported that several selective protein kinase C inhibitors promote the growth of murine hair epithelial cells and stimulate anagen induction. In this paper, we report on an investigation of the mechanisms of action of hair-growing activity possessed by cyclosporin A from the viewpoint of whether it promotes hair epithelial cell growth or whether it modulates the expression or translocation of protein kinase C isozymes in hair epithelial cells. Our results indicate that cyclosporin A (over a wide dosage range of 1-1000 ng per ml) stimulates cultured murine hair epithelial cell growth to about 150%-160% relative to controls. We also observed growth-promoting effects on murine epidermal keratinocytes (about 140%) at the dose range of 1-100 ng per ml. At high dose ranges above 3 microg per ml, the growth of both cells was inhibited. On the other hand, we found that cyclosporin A reduces the overall expression of protein kinase C alpha, betaI, and betaII in cultured murine hair epithelial cells, and reduces the levels of protein kinase C alpha, betaI, betaII, and eta in the particulate fraction from cultured murine hair epithelial cells. From these results, we speculate that the hair-growing activity of cyclosporin A is at least partially attributable to its growth-promoting influence on hair epithelial cells sequential to its downregulation of some protein kinase C isozymes in hair epithelial cells or inhibition of translocation of some protein kinase C isozymes to the membrane or cytoskeleton of hair epithelial cells.
Takahashi
T
T
Tsukuba Research Laboratories, Kyowa Hakko Kogyo Co., Tsukuba, Ibaraki, Japan. tomoya.takahashi@kyowa.co.jp
Kamimura
A
A
D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D016572:Cyclosporine / Q000494:pharmacology*; D003879:Dermatologic Agents / Q000494:pharmacology*; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology; D006197:Hair / Q000166:cytology* / Q000502:physiology; D051379:Mice; D011493:Protein Kinase C / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects
D003879:Dermatologic Agents; D016572:Cyclosporine; D011493:Protein Kinase C