title: Influence of interleukin-1alpha 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-1alpha (IL-1alpha) is prominent in skin wounding and inflammatory responses although regarded as a negative hair growth regulator. We studied the effect of IL-1alpha and the potent androgen 5alpha-dihydrotestosterone (DHT) on the expression of the androgen receptor (AR) and various factors secreted by cultured human temporal scalp DPC. IL-1alpha triggered cellular changes consistent with nuclear factor-kappaB 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-1alpha did not influence DPC supernatant levels of transforming growth factor-beta1, a negative hair growth regulator. The stimulatory effect of IL-1alpha on DPC VEGF, GM-CSF, KGF, and IL-8 expression was also evident at the mRNA level for these cytokines. IL-1alpha 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-1alpha. In consideration of its in vitro activity profile, IL-1alpha may be an important modifier of dermal papilla activity as well as potentially influence androgen-regulated gene expression in DPC.
authors.affiliation: Scientific Affairs: Dermatology, QLT Inc., 887 Great Northern Way, Vancouver, British Columbia, Canada.
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Boivin
authors.forename: Huijun
authors.initials: H
authors.lastname: Jiang
authors.forename: Oliver B
authors.initials: OB
authors.lastname: Utting
authors.forename: David W C
authors.initials: DW
authors.lastname: Hunt
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D013196:Dihydrotestosterone / Q000494:pharmacology; D051523:Fibroblast Growth Factor 7 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D006197:Hair / Q000254:growth & development; D018859:Hair Follicle / Q000378:metabolism; D006801:Humans; D053582:Interleukin-1alpha / Q000502:physiology*; D008297:Male; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D058255:Protease Nexins; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D058258:Serpin E2; D012867:Skin / Q000166:cytology / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D016207:Cytokines; D053582:Interleukin-1alpha; D016328:NF-kappa B; D058255:Protease Nexins; D012333:RNA, Messenger; D011944:Receptors, Androgen; D011956:Receptors, Cell Surface; C545486:SERPINE2 protein, human; D058258:Serpin E2; D042461:Vascular Endothelial Growth Factor A; D013196:Dihydrotestosterone; D051523:Fibroblast Growth Factor 7; D016178:Granulocyte-Macrophage Colony-Stimulating Factor