Influence of interleukin‐1α on androgen receptor expression and cytokine secretion by cultured human dermal papilla cells

Abstract: Dermal papilla cells (DPC) control the growth character of the hair follicle through their elaboration of mitogenic factors and extracellular matrix components. Further, the dermal papilla is a primary site of androgen action in the hair follicle. Interleukin‐1 α (IL‐1 α ) is prominent in skin wounding and inflammatory responses although regarded as a negative hair growth regulator. We studied the effect of IL‐1 α and the potent androgen 5 α ‐dihydrotestosterone (DHT) on the expression of the androgen receptor (AR) and various factors secreted by cultured human temporal scalp DPC. IL‐1 α triggered cellular changes consistent with nuclear factor‐ κ B pathway activation as well as reduced AR mRNA and protein expression levels for DHT‐stimulated DPC. This cytokine also increased DPC supernatant keratinocyte growth factor (KGF), vascular endothelial growth factor (VEGF), IL‐8 and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) concentrations. IL‐1 α did not influence DPC supernatant levels of transforming growth factor‐ β 1, a negative hair growth regulator. The stimulatory effect of IL‐1 α on DPC VEGF, GM‐CSF, KGF, and IL‐8 expression was also evident at the mRNA level for these cytokines. IL‐1 α also increased mRNA transcript levels of protease‐nexin‐1, a secreted serine protease inhibitor expressed in the dermal papilla of anagen‐stage hair follicles. Although DHT did not affect supernatant cytokine concentrations, the androgen altered mRNA transcript levels of several factors for DPC co‐stimulated with IL‐1 α . In consideration of its in vitro activity profile, IL‐1 α may be an important modifier of dermal papilla activity as well as potentially influence androgen‐regulated gene expression in DPC.