CARMA3 Mediates Allergic Lung Inflammation in Response to Alternaria alternata.
Am J Respir Cell Mol Biol
; 59(6): 684-694, 2018 12.
Article
em En
| MEDLINE
| ID: mdl-29958012
ABSTRACT
The airway epithelial cell (AEC) response to allergens helps initiate and propagate allergic inflammation in asthma. CARMA3 is a scaffold protein that mediates G protein-coupled receptor-induced NF-κB activation in airway epithelium. In this study, we demonstrate that mice with CARMA3-deficient AECs have reduced airway inflammation, as well as reduced type 2 cytokine levels in response to Alternaria alternata. These mice also have reduced production of IL-33 and IL-25, and reduced numbers of innate lymphoid cells in the lung. We also show that CARMA3-deficient human AECs have decreased production of proasthmatic mediators in response to A. alternata. Finally, we show that CARMA3 interacts with inositol 1,4,5-trisphosphate receptors in AECs, and that inhibition of CARMA3 signaling reduces A. alternata-induced intracellular calcium release. In conclusion, we show that CARMA3 signaling in AECs helps mediate A. alternata-induced allergic airway inflammation, and that CARMA3 is an important signaling molecule for type 2 immune responses in the lung.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pneumonia
/
Asma
/
Alérgenos
/
Proteínas Adaptadoras de Sinalização CARD
/
Alternaria
/
Alternariose
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article