Phorbol-myristate-acetate, but not interleukin-1 beta or insulin-like growth factor-I, regulates protein kinase C isoenzymes in human dermal papilla cells.

Abstract

The in vitro growth of human hair follicles is inhibited by interleukin (IL)-1 beta and phorbol esters, such as phorbol-myristate-acetate (PMA), but enhanced by insulin-like growth factor (IGF)-I. Although this process is only incompletely understood, the dermal papilla as a pivotal part of the hair follicle is almost certainly involved. Since protein kinase C (PKC) isoenzymes are activated by phorbol esters and are key enzymes in signalling pathways of several hormones, neurotransmitters, and growth factors, we addressed the question whether the action of the above-mentioned hair growth-modulating substances may affect PKC isoenzymes in cultured dermal papilla cells (DPC). By Western blot analysis, protein kinase C alpha, -epsilon, -gamma, -iota, -lambda, and the RACK1 receptor protein were detected in dermal papilla cell cultures, whereas the isoenzymes delta and mu were expressed only at low levels and protein kinase C-beta, -theta, and -zeta, were not present. After PMA stimulation, the PKC alpha, -epsilon, and -gamma were translocated from the cytosol to the membrane fraction and subsequently down-regulated. PKC iota was down-regulated but not translocated, and PKC lambda and RACK1 were not affected by PMA. Neither, IL-1 beta nor IGF had an effect on PKC or RACK1 expression. We conclude that cultured DPC express a distinct PKC isoenzyme pattern and that the PMA-induced growth arrest in cultivated hair follicles may be transmitted via protein kinases, whereas the effects of IL-1 beta or IGF may be transduced via other signal transduction pathways or other cell types.