Interferon-γ is a potent inducer of catagen-like changes in cultured human anagen hair follicles

T. Ito, N. Ito, M. Saathoff, A. Bettermann, M. Takigawa, Ralf Paus

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)623-631
Number of pages9
JournalBritish Journal of Dermatology
Volume152
Issue number4
DOIs
StatePublished - Apr 1 2005
Externally publishedYes

Fingerprint

Hair Follicle
Interferons
Hair
Interferon Receptors
Transforming Growth Factors
Scalp
Pigmentation
Growth
Apoptosis
In Situ Nick-End Labeling
Keratinocytes
Reverse Transcription
Fluorescent Antibody Technique
Intercellular Signaling Peptides and Proteins
Up-Regulation
Phosphates

Keywords

  • Anagen
  • Catagen
  • Interferon-γ
  • Interferon-γ receptor
  • Transforming growth factor-β2

ASJC Scopus subject areas

  • Dermatology

Cite this

Interferon-γ is a potent inducer of catagen-like changes in cultured human anagen hair follicles. / Ito, T.; Ito, N.; Saathoff, M.; Bettermann, A.; Takigawa, M.; Paus, Ralf.

In: British Journal of Dermatology, Vol. 152, No. 4, 01.04.2005, p. 623-631.

Research output: Contribution to journalArticle

Ito, T. ; Ito, N. ; Saathoff, M. ; Bettermann, A. ; Takigawa, M. ; Paus, Ralf. / Interferon-γ is a potent inducer of catagen-like changes in cultured human anagen hair follicles. In: British Journal of Dermatology. 2005 ; Vol. 152, No. 4. pp. 623-631.
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AU - Ito, N.

AU - Saathoff, M.

AU - Bettermann, A.

AU - Takigawa, M.

AU - Paus, Ralf

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N2 - 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.

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