363 CRH is a stimulator for both connective tissue- and mucosal-type mast cells

Abstract

It is well-known that psychological stress exacerbates various types of diseases including atopic dermatitis and allergic rhinitis. One of crucial cells in immune responses, mast cell (MC)s, are activated in those diseases and play central roles in their pathogenesis. Hypothalamic-pituitary-adrenal (HPA) axis is an essential endocrine system of reaction to stress. However, the existence of local HPA axis is also reported within the human skin. Among the HPA axis-related hormone, corticotropin-releasing hormone (CRH) is regarded as a potent central stress mediator. We have previously shown that the locally secreted CRH activates connective tissue type MCs (CT-MC)s degranulation and differentiation by organ cultured human hair follicles (HF)s. Here, we focused on the effect of CRH on mucosal-type (M-)MCs biology compared to CT-MCs. Using the previously established human nasal polyp organ culture, CRH was detected both in gene and protein levels. CRH significantly enhanced the expression of both melanocortin 2 receptor and glucocorticoid receptor, while hydrocortisone decreased CRH receptor expression, suggesting the presence of positive and negative feedback system as seen in human HFs. Similar with CT-MCs, CRH significantly increased M-MCs number and stimulated degranulation. In contrast to CT-MCs, CRH enhanced M-MCs proliferation. Just seen in human HFs, CRH increased the expression of stem cell factor (SCF), a growth factor for MCs, suggesting that SCF is also involved in CRH-induced M-MCs activation. Finally, we checked M-MCs in nasal mucosa of chronic restraint stress model mouse. As a result, the number of degranulated MCs significantly increased in nasal mucosa. Current results suggest that the local HPA axis exists not only in human skin but also in nasal mucosa. Since CRH is a stimulator for both CT-MCs and M-MCs, controlling of HPA axis-related hormones may be a key target for establishing novel therapy for atopic dermatitis and allergic rhinitis.