Taurodeoxycholate, a GPCR19 agonist, ameliorates atopic dermatitis in Balb/c mice.
Eur J Immunol
; 53(5): e2250048, 2023 05.
Article
em En
| MEDLINE
| ID: mdl-36815313
ABSTRACT
Keratinocytes are pivotal cells in the pathogenesis of atopic dermatitis (AD) as much as Th2 cells. In this sense, regulation of pro-inflammatory features of keratinocytes might be useful for AD patients. P2X7R-mediated activation of NLRP3 inflammasome (N3I) in keratinocytes and myeloid cells plays crucial roles in AD. Nonetheless, inhibition of P2X7R has not been feasible because of polymorphisms and ubiquitous expression of P2X7R. Here, we report that GPCR19 colocalizes with P2X7R, and a GPCR19 agonist (taurodeoxycholate [TDCA]) inhibits the activation of P2X7R. Noncistronically, TDCA inhibits NF-kB activation via the adenylate cyclase-PKA pathway and BzATP-mediated Ca++ mobilization. Cistronically, TDCA suppresses the expression of P2X7R and N3I components in keratinocytes. NLRP3 oligomerization and the production of mature IL-1ß and IL-18 was suppressed by TDCA treatment in keratinocytes. Topical TDCA treatment ameliorates proinflammatory features of AD in mice induced by DNCB, MC903, or oxazolone. Taken together, a GPCR19 agonist such as TDCA might inhibit P2X7R-mediated N3I activation of keratinocytes, which is crucial for the pathogenesis of AD.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Dermatite Atópica
Limite:
Animals
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article