Glucagon-like peptide-1 receptor agonist inhibits aeroallergen-induced activation of ILC2 and neutrophilic airway inflammation in obese mice.
Allergy
; 76(11): 3433-3445, 2021 11.
Article
em En
| MEDLINE
| ID: mdl-33955007
ABSTRACT
BACKGROUND:
Obesity is a risk factor for the development of asthma. However, pharmacologic therapeutic strategies that specifically target obese asthmatics have not been identified. We hypothesize that glucagon-like peptide-1 receptor agonist (GLP-1RA) treatment inhibits aeroallergen-induced early innate airway inflammation in a mouse model of asthma in the setting of obesity.METHODS:
SWR (lean) and TALLYHO (obese) mice were challenged intranasally with Alternaria alternata extract (Alt-Ext) or PBS for 4 consecutive days concurrent with GLP-1RA or vehicle treatment.RESULTS:
TALLYHO mice had greater Alt-Ext-induced airway neutrophilia and lung protein expression of IL-5, IL-13, CCL11, CXCL1, and CXCL5, in addition to ICAM-1 expression on lung epithelial cells compared with SWR mice, and all endpoints were reduced by GLP-1RA treatment. Alt-Ext significantly increased BALF IL-33 in both TALLYHO and SWR mice compared to PBS challenge, but there was no difference in the BALF IL-33 levels between these two strains. However, TALLYHO, but not SWR, mice had significantly higher airway TSLP in BALF following Alt-Ext challenge compared to PBS, and BALF TSLP was significantly greater in TALLYHO mice compared to SWR mice following airway Alt-Ext challenge. GLP-1RA treatment significantly decreased the Alt-Ext-induced TSLP and IL-33 release in TALLYHO mice. While TSLP or ST2 inhibition with a neutralizing antibody decreased airway eosinophils, they did not reduce airway neutrophils in TALLYHO mice.CONCLUSIONS:
These results suggest that GLP-1RA treatment may be a novel pharmacologic therapeutic strategy for obese persons with asthma by inhibiting aeroallergen-induced neutrophilia, a feature not seen with either TSLP or ST2 inhibition.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Receptor do Peptídeo Semelhante ao Glucagon 1
/
Imunidade Inata
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article