Ann Dermatol.  2022 Aug;34(4):270-277. 10.5021/ad.21.161.

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

• Kim C
• Shin JM
• Kim D
• Park S
• Hong D
• Jung KE
• Kim CD
• Seo YJ
• Lee Y

• KMID: 2531874
• DOI: http://doi.org/10.5021/ad.21.161

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 growthrelated 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 inf lammatory response, and inhibited hair growth, thereby confirming the pathogenic role of SP in AA.

Keyword

Alopecia areata; Pathogenesis; Substance P