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Notes: Background  Interferon (IFN)-γ 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-γ 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-γ affects human hair growth in vivo. This was correlated with the hair follicle expression patterns of IFN-γ receptors α and β. 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-γ (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-γ receptors were also localized by immunofluorescence and EnVision technique. As transforming growth factor (TGF)-β2 is a recognized key inducer of catagen in human hair follicles, TGF-β2 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-γ.Results  IFN-γ 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-β2). Proliferation was inhibited, apoptosis was increased and follicular melanogenesis was switched off in hair bulb keratinocytes treated in situ with IFN-γ. Anagen hair follicles displayed strong IFN-γ receptor α-like immunoreactivity, while the immunoreactivity for IFN-γ receptor β in the hair matrix was only weak. TGF-β2 immunoreactivity and mRNA transcript levels were enhanced in hair follicles treated with IFN-γ.Conclusions  These data suggest that IFN-γ is a potent catagen inducer in normal human scalp hair follicles, which express cognate receptors, and show that IFN-γ 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-β2.

Notes: The functional role of VR1, which we and others have recently identified on several epithelial and mesenchymal human skin cell populations, was investigated in the human hair follicle (HF), as a prototypic epithelial–mesenchymal interaction system. VR1 immunoreactivity was confined to distinct epithelial compartments of HFs in anagen and catagen, while dermal papilla fibroblasts and HF melanocytes were VR1 negative. In organ culture, VR1 activation by capsaicin resulted in a dose-dependent and VR1-specific inhibition of hair shaft elongation, suppression of proliferation, promotion of apoptosis, and induction of catagen transformation, possibly due to upregulation of a potent hair growth inhibitor TGFβ2. Cultured outer root sheath (ORS), as well as HaCaT, keratinocytes also expressed functional VR1, whose stimulation inhibited proliferation, induced apoptosis, and elevated intracellular calcium concentration. Finally, VR1 stimulation of cultured ORS keratinocytes upregulated the expression of recognized endogenous hair growth inhibitors (IL-1β and TGFβ2) and downregulated the expression of stimulators (HGF, IGF-1, and SCF), while key differentiation markers (CK17, CK14, filaggrin, and involucrin) remained unaffected. In conclusion, VR1 is a significant novel player in human hair growth control underscoring that its physiological functions in human skin far extend beyond sensory neuron-coupled nociception.