Interferon-gamma is a potent inducer of catagen-like changes in cultured human anagen hair follicles.
Interferon-gamma is a potent inducer of catagen-like changes in cultured human anagen hair follicles.
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发表时间：
2005
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通讯作者：
T. Ito;N. Ito;M. Saathoff;A. Bettermann;M. Takigawa;R. Paus
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作者：
T. Ito;N. Ito;M. Saathoff;A. Bettermann;M. Takigawa;R. Paus
干扰素（IFN）-γ似乎是小鼠中重要的毛发周期调节剂。目前还不清楚它是否在人类毛囊中具有类似的毛发生长调节功能。目的研究IFN-γ是否可用于调节器官培养的人毛发生长期头皮毛囊的生长、色素沉着和/或周期，作为IFN-γ如何影响体内人毛发生长的体外指示系统。这与IFN-γ受体α和β的毛囊表达模式相关。此外，我们希望建立一个新的，简单的工具，在体外快速实验诱导退行期。方法按照Philpott等人的方法培养处于毛发周期生长期VI阶段的正常人头皮毛囊，有或没有IFN-γ（50-1000 IU mL（-1））。测量毛干伸长和色素沉着变化，辅以定量组织形态计量学，以评估毛囊周期（毛发周期评分）、增殖（Ki-67）、黑素生成（Masson-Fontana）和凋亡（TUNEL）的变化。还通过免疫荧光和EnVision技术定位IFN-γ受体。由于转化生长因子（TGF）-β 2是公认的人毛囊退行期的关键诱导剂，因此通过酪胺信号放大和逆转录-聚合酶链反应研究了用溶剂（磷酸盐缓冲盐水）或IFN-γ处理的生长期毛囊中TGF-β 2的表达。结果IFN-γ在培养的人毛发生长期毛囊中迅速抑制毛发伸长，并且仅在培养4天后就诱导退行期转化的形态学迹象，即比其他报道的退行期诱导剂（例如TGF-β 2）更快。在用IFN-γ原位处理的毛球角质形成细胞中，增殖被抑制，凋亡增加，滤泡黑素生成被关闭。生长期毛囊显示出强烈的IFN-γ受体α样免疫反应性，而IFN-γ受体β在头发基质中的免疫反应性仅为弱。TGF-β 2免疫反应性和mRNA转录水平在IFN-γ处理的毛囊中增强。结论：这些数据表明，IFN-γ是一种有效的退行期诱导剂在正常人头皮毛囊，表达同源受体，并显示，IFN-γ管理提供了一个很好的工具，实验退行期诱导器官培养的人毛囊。这种退行期诱导可能至少部分通过上调公认的退行期刺激生长因子TGF-β 2而发生。
BACKGROUND Interferon (IFN)-gamma appears to be an important hair cycle modulator in mice. It is unclear whether it has similar hair growth modulatory functions in human hair follicles. OBJECTIVES To study whether IFN-gamma can be exploited to modulate the growth, pigmentation and/or cycling of organ-cultured human anagen scalp hair follicles, as an in vitro indicator system for how IFN-gamma affects human hair growth in vivo. This was correlated with the hair follicle expression patterns of IFN-gamma receptors alpha and beta. In addition, we wanted to establish a new, simple tool for the rapid experimental induction of catagen in vitro. METHODS Normal human scalp hair follicles in the anagen VI stage of the hair cycle were cultured according to the method of Philpott et al., with or without IFN-gamma (50-1000 IU mL(-1)). Hair shaft elongation and pigmentation changes were measured, complemented by quantitative histomorphometry to assess changes in hair follicle cycling (hair cycle score), proliferation (Ki-67), melanogenesis (Masson-Fontana) and apoptosis (TUNEL). IFN-gamma receptors were also localized by immunofluorescence and EnVision technique. As transforming growth factor (TGF)-beta2 is a recognized key inducer of catagen in human hair follicles, TGF-beta2 expression was investigated by tyramide signal amplification and reverse transcription-polymerase chain reaction in anagen hair follicles treated with vehicle (phosphate-buffered saline) or IFN-gamma. RESULTS IFN-gamma rapidly inhibited hair elongation in cultured human anagen hair follicles and induced morphological signs of catagen transformation after only 4 days of culture, i.e. faster than with other reported catagen-inducers (e.g. TGF-beta2). Proliferation was inhibited, apoptosis was increased and follicular melanogenesis was switched off in hair bulb keratinocytes treated in situ with IFN-gamma. Anagen hair follicles displayed strong IFN-gamma receptor alpha-like immunoreactivity, while the immunoreactivity for IFN-gamma receptor beta in the hair matrix was only weak. TGF-beta2 immunoreactivity and mRNA transcript levels were enhanced in hair follicles treated with IFN-gamma. CONCLUSIONS These data suggest that IFN-gamma is a potent catagen inducer in normal human scalp hair follicles, which express cognate receptors, and show that IFN-gamma administration offers an excellent tool for experimental catagen induction in organ-cultured human hair follicles. This catagen induction probably occurs at least in part via upregulation of the recognized catagen-stimulatory growth factor TGF-beta2.