Probing the effects of stress mediators on the human hair follicle: substance P holds central position.
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 beta2-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.
Department of Dermatology, University Hospital Schleswig-Holstein, University of Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany.
Eva M J
EM
Peters
Sofia
S
Liotiri
Eniko
E
Bodó
Evelin
E
Hagen
Tamás
T
Bíró
Petra C
PC
Arck
Ralf
R
Paus
D001681:Biological Assay; D015550:Cell Degranulation; D018859:Hair Follicle / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology; D020932:Nerve Growth Factor / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064729:Neurokinin-1 Receptor Antagonists; D020917:Receptor, trkA / Q000037:antagonists & inhibitors / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D012535:Scalp / Q000187:drug effects* / Q000378:metabolism; D013312:Stress, Physiological / Q000378:metabolism*; D013373:Substance P / Q000494:pharmacology*; D015854:Up-Regulation
D015395:Histocompatibility Antigens Class I; C484065:NGFR protein, human; D009419:Nerve Tissue Proteins; D064729:Neurokinin-1 Receptor Antagonists; D017475:Receptors, Nerve Growth Factor; D018040:Receptors, Neurokinin-1; D013373:Substance P; D020932:Nerve Growth Factor; D020917:Receptor, trkA