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 m echanisms of action that cause hirsutism. have not been fully elucidated, h owever. We have previously reported that several selective protein kinase C inhibitors promote the growth of murine hair epithelial cells and stimulat e anagen induction. In this paper, we report on an investigation of the mec hanisms 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 epit helial cell growth to about 150%-160% relative to controls. We also observe d growth-promoting effects on murine epidermal keratinocytes (about 140%) a t the dose range of 1-100 ng per ml. At high dose ranges above 3 mug 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, bet aI, and PH in cultured murine hair epithelial cells, and reduces the levels of protein kinase C alpha, betaI, beta II, and il in the particulate fract ion from cultured murine hair epithelial cells. From these results, we spec ulate that the hair-growing activity of cyclosporin A is at least partially attributable to its growth-promoting influence on hair epithelial cells se quential to its downregulation of some protein kinase C isozymes. in hair e pithelial cells or inhibition of translocation of some protein kinase C iso zymes to the membrane or cytoskeleton of hair epithelial cells.