title: Interleukin-1beta is differentially expressed by human dermal papilla cells in response to PKC activation and is a potent inhibitor of human hair follicle growth in organ culture.
abstract: The dermal papilla plays an important role in the regulation of hair follicle matrix cell proliferation and hair fiber production, at least in part through mesenchymal-epithelial interactions. In the present study, we have investigated the regulation of interleukin-1 (IL-1) production by protein kinase C in cultured human dermal papilla cells. Treatment of dermal papilla cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) elicited the rapid and transient production of mature (17 kDa) cytosolic IL-1beta protein, but not IL-1alpha, with maximal levels achieved after 12 h. Rapid secretion of IL-1beta into the medium occurred subsequent to increased intracellular cytokine levels, after which medium IL-1beta protein levels were stable for 4 days. Northern blot analysis showed that TPA treatment elicited a transient induction of IL-1beta mRNA expression, maximal after 12 h, indicating that TPA regulates dermal papilla cell IL-1beta production at the transcriptional level. Pretreatment of dermal papilla cells with Ro 31-7549, a selective protein kinase C inhibitor, dose dependently and completely reversed phorbol-induced IL-1beta protein production. In addition, we demonstrated that IL-1beta is a highly potent inhibitor of the growth of human hair follicles in whole-organ culture, with an IC50 value of approximately 5 pg/ml. These findings, taken together with a previous report that follicular matrix cells express type I IL-1 receptors but dermal papilla cells do not, raise the possibility that dermal papilla cell-derived IL-1beta may act as a negative paracrine factor in the regulation of matrix cell proliferation.
authors.affiliation: Preclinical Dermatology Research, Hoffmann-La Roche, Nutley, NJ 07110, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Xiong
authors.forename: C S
authors.initials: CS
authors.lastname: Harmon
mesh_terms: D002478:Cells, Cultured; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006131:Growth Inhibitors / Q000096:biosynthesis* / Q000378:metabolism; D018859:Hair Follicle / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000378:metabolism; D008301:Maleimides / Q000494:pharmacology; D009924:Organ Culture Techniques; D011493:Protein Kinase C / Q000187:drug effects*; D012867:Skin / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D006131:Growth Inhibitors; D007211:Indoles; D007375:Interleukin-1; D008301:Maleimides; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; C064755:Ro 31-7549