Role of Substance P in Regulating Micro-Milieu of Inflammation in Alopecia Areata

Abstract

Background Alopecia areata (AA) is an autoimmune disease characterized by chronic inflammation, the pathogenesis of which is unknown. Stress is believed to play a role; however, evidence remains insufficient. A recent study showed that substance P (SP) damaged hair follicles by causing neurogenic inflammation, activating perifollicular mast cells, and inducing keratinocyte apoptosis. Objective We aimed at studying the role of SP in AA pathogenesis. We investigated the SP levels in the lesional scalp tissues and serum. We also studied the effect of SP on the inflammatory response and hair growth in the outer root sheath (ORS) cells. Methods We compared the serum levels of SP in 58 AA patients and 28 healthy subjects. Then, we checked the expression of SP and SP receptor, neurokinin-1 receptor (NK-1R) in the scalps of AA patients and healthy controls using immunohistochemical staining. Finally, we analyzed the mRNA expression of inflammatory cytokines and hair growth-related factors in ORS cells. Results SP and NK-1R expression were markedly higher in the hair follicles and interfollicular epidermis of the scalp lesions of AA patients. However, there was no statistically significant difference in serum SP levels between controls and patients, regardless of the type of alopecia. SP significantly increased the mRNA expression of inflammatory cytokines and decreased hair growth-related growth factors in ORS cells, but the results were not dramatic. Conclusion SP triggered a localized micro-inflammation in lesional hair follicles, provoked an inflammatory response, and inhibited hair growth, thereby confirming the pathogenic role of SP in AA.

Role of neurogenic inflammation in the pathogenesis of alopecia areata

“…The levels of SP and neurokinin‐1 receptor (NK‐1R) expression were observably upper in scalp lesion's HFs and interfollicular epidermis of AA patients. In contrast, there was no notable disparity observed in serum SP levels between AA patients and individuals in the control group 41 . CGRP levels of lesional AA skin 42 and plasma CGRP levels in AA patients were decreased 43 .…”

“…In contrast, there was no notable disparity observed in serum SP levels between AA patients and individuals in the control group. 41 CGRP levels of lesional AA skin 42 and plasma CGRP levels in AA patients were decreased. 43 At the same time, studies have shown that HPA axis modification, characterized by CRH/CRH receptor (CRH-R) enhancement and glucocorticoid deficiency, takes part in the pathological process of AA.…”

“…Previous research suggested that the effects of SP on AA patients are likely localized rather than systemic 41 . Studies in mouse models found an increase in the count of SP immunoreactive nerves in the skin early in AA disease.…”

“…48 Previous research suggested that the effects of SP on AA patients are likely localized rather than systemic. 41 Studies in mouse models found an increase in the count of SP immunoreactive nerves in the skin early in AA disease. In the advanced stage of AA, there was a decrease in the count of nerves expressing SP immunopositivity and a reduction in the level of SP protein present in the skin.…”

Psychological Stress-Induced Pathogenesis of Alopecia Areata: Autoimmune and Apoptotic Pathways

“…Neuropeptides, which are secreted in response to psychological stress, such as SP and CRH, participate in the induction of AA [21,22]. SP is a tachykinin neuropeptide composed of 11 amino acids [23].…”