Influence of interleukin-1α on androgen receptor expression and cytokine secretion by cultured human dermal papilla cells
Influence of interleukin-1α on androgen receptor expression and cytokine secretion by cultured human dermal papilla cells
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DOI：
10.1111/j.1600-0625.2006.00462.x
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发表时间：
2006-10-01
影响因子：
3.6
通讯作者：
Hunt, David W. C.
中科院分区：
文献类型：
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作者：
Boivin, Wendy A.;Jiang, Huijun;Hunt, David W. C.
毛乳头细胞（DPC）通过分泌促有丝分裂因子和细胞外基质成分控制毛囊的生长。此外，毛乳头是毛囊中雄激素作用的主要部位。白细胞介素-1 α（IL-1 α）在皮肤创伤和炎症反应中是突出的，尽管被认为是负性毛发生长调节剂。我们研究了IL-1 α和强效雄激素5 α-二氢睾酮（DHT）对培养的人颞部头皮DPC分泌的雄激素受体（AR）和各种因子表达的影响。IL-1 α引发的细胞变化与核因子-κ B通路活化以及DHT刺激的DPC的AR mRNA和蛋白表达水平降低一致。该细胞因子还增加DPC上清液角质形成细胞生长因子（KGF）、血管内皮生长因子（VEGF）、IL-8和粒细胞-巨噬细胞集落刺激因子（GM-CSF）的浓度。IL-1 α不影响DPC上清液中转化生长因子-β 1（一种负性毛发生长调节因子）的水平。IL-1 α对DPC VEGF、GM-CSF、KGF和IL-8表达的刺激作用在这些细胞因子的mRNA水平上也是明显的。IL-1 α还增加了蛋白酶-连接蛋白-1的mRNA转录水平，这是一种分泌型丝氨酸蛋白酶抑制剂，在生长期毛囊的毛乳头中表达。虽然DHT不影响上清液中细胞因子的浓度，雄激素改变了DPC与IL-1 α共刺激的几个因子的mRNA转录水平。考虑到其体外活性特征，IL-1 α可能是毛乳头活性的重要修饰剂，并可能影响DPC中雄激素调节的基因表达。
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 alpha (IL-1 alpha) is prominent in skin wounding and inflammatory responses although regarded as a negative hair growth regulator. We studied the effect of IL-1 alpha and the potent androgen 5 alpha-dihydrotestosterone (DHT) on the expression of the androgen receptor (AR) and various factors secreted by cultured human temporal scalp DPC. IL-1 alpha triggered cellular changes consistent with nuclear factor-kappa 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 alpha did not influence DPC supernatant levels of transforming growth factor-beta 1, a negative hair growth regulator. The stimulatory effect of IL-1 alpha on DPC VEGF, GM-CSF, KGF, and IL-8 expression was also evident at the mRNA level for these cytokines. IL-1 alpha 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 alpha. In consideration of its in vitro activity profile, IL-1 alpha may be an important modifier of dermal papilla activity as well as potentially influence androgen-regulated gene expression in DPC.