Interleukin-1β 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

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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-1β protein, but not IL-1α, with maximal levels achieved after 12 h. Rapid secretion of IL-1β into the medium occurred subsequent to increased intracellular cytokine levels, after which medium IL-1β protein levels were stable for 4 days. Northern blot analysis showed that TPA treatment elicited a transient induction of IL-1β mRNA expression, maximal after 12 h, indicating that TPA regulates dermal papilla cell IL-1β 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-1β protein production. In addition, we demonstrated that IL-1β 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 IL1β may act as a negative paracrine factor in the regulation of matrix cell proliferation.