Probing the effects of stress mediators on the human hair follicle: Substance P holds central position

Eva M.J. Peters, Sofia Liotiri, Eniko Bodó, Evelin Hagen, Tamás Bíró, Petra C. Arck, Ralf Paus

Research output: Contribution to journalArticle

114 Scopus citations

Abstract

Stress alters murine hair growth, depending on substance P-mediated neurogenic inflammation and nerve growth factor (NGF), a key modulator of hair growth termination (catagen induction). Whether this is of any relevance in human hair follicles (HFs) is completely unclear. Therefore, we have investigated the effects of substance P, the central cutaneous prototypic stress-associated neuropeptide, on normal, growing human scalp HFs in organ culture. We show that these prominently expressed substance P receptor (NK1) at the gene and protein level. Organ-cultured HFs responded to substance P by premature catagen development, down-regulation of NK1, and up-regulation of neutral endopeptidase (degrades substance P). This was accompanied by mast cell degranulation in the HF connective tissue sheath, indicating neurogenic inflammation. Substance P down-regulated immunoreactivity for the growth-promoting NGF receptor (TrkA), whereas it up-regulated NGF and its apoptosis- and catagen-promoting receptor (p75NTR). In addition, MHC class I and β2-microglobulin immunoreactivity were up-regulated and detected ectopically, Indicating collapse of the HF immune privilege. In conclusion, we present a simplistic, but instructive, organ culture assay to demonstrate sensitivity of the human HF to key skin stress mediators. The data obtained therewith allow one to sketch the first evidence-based biological explanation for how stress may trigger or aggravate telogen effluvium and alopecia areata.

Original languageEnglish (US)
Pages (from-to)1872-1886
Number of pages15
JournalAmerican Journal of Pathology
Volume171
Issue number6
DOIs
StatePublished - Dec 2007
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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