Serum level of hemokinin-1 is significantly lower in patients with chronic spontaneous urticaria than in healthy subjects.
Allergol Int
; 70(4): 480-488, 2021 Oct.
Article
em En
| MEDLINE
| ID: mdl-34090787
ABSTRACT
BACKGROUND:
We previously reported upregulation of expression of Mas-related G protein-coupled receptor X2 (MRGPRX2) on mast cells (MCs) in the skin of patients with severe chronic spontaneous urticaria (CSU). Serum levels of substance P (SP) were reportedly significantly elevated, in correlation with the severity of CSU. Hemokinin-1 (HK-1) reportedly induced histamine release from LAD2 cells via MRGPRX2. We aimed to investigate HK-1's role in CSU.METHODS:
The concentrations of HK-1 and SP were measured using ELISAs. Skin- and synovium-derived cultured MCs were generated by culturing dispersed skin and synovial cells, respectively, with stem cell factor. MRGPRX2 expression in the MCs was reduced using a lentiviral shRNA silencing technique.RESULTS:
Anti-SP Ab used in the SP ELISA showed 100% cross-reactivity to HK-1, but anti-HK-1 Ab showed 0% cross-reactivity to SP. The serum level of HK-1 was significantly lower in patients with CSU (n = 151) than in non-atopic healthy control (NC) subjects (n = 114). The EC50 of histamine release from MCs induced by HK-1 (5056 nM) was 12-fold higher than by SP (426 nM). Brief pretreatment of MCs with HK-1 at concentrations of 3.0-10 µM significantly reduced histamine release by 0.1 µM SP. However, brief incubation of MCs with HK-1 did not elicit rapid MRGPRX2 internalization.CONCLUSIONS:
In NC subjects, high HK-1 concentrations may desensitize MGRPRX2-mediated MC activation, thereby preventing MC degranulation by SP.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Taquicininas
/
Urticária Crônica
Limite:
Adolescent
/
Adult
/
Aged
/
Aged80
/
Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Allergol Int
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Japão