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.
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.
Xiong
Y
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Preclinical Dermatology Research, Hoffmann-La Roche, Nutley, NJ 07110, USA.
Harmon
C S
CS
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*
D004791:Enzyme Inhibitors; D006131:Growth Inhibitors; D007211:Indoles; D007375:Interleukin-1; D008301:Maleimides; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; C064755:Ro 31-7549