Isatin down-regulates expression of atrial natriuretic peptide receptor A and inhibits airway inflammation in a mouse model of allergic asthma.
Int Immunopharmacol
; 10(2): 218-25, 2010 Feb.
Article
em En
| MEDLINE
| ID: mdl-19900583
ABSTRACT
Isatin, an endogenous indole compound, prevents atrial natriuretic peptide (ANP) from signaling through its cell-surface receptor, NPRA. Allergic airway inflammation has been linked to natriuretic peptide signaling and blocking this signaling axis in the lung prevents allergen-induced pathology. In this study we encapsulated isatin in chitosan nanoparticles and tested them in a mouse model of allergic asthma by intranasal delivery to the lung. Isatin nanocapsules reduced lung pathology by blocking ANP signaling, but surprisingly also by reducing the expression of NPRA. Ovalbumin-allergic mice were treated intranasally with isatin-containing chitosan nanocapsules either before or after allergen challenge, and lung function, cytokine levels, histopathology and cellular infiltration were determined. ANP activity was quantitated by measuring changes in intracellular cyclic GMP and changes in NPRA levels were determined. For comparison with isatin's effects, the expression of the receptor was inhibited with small interfering RNA against NPRA mRNA. Isatin nanocapsules administered locally to the lung reduced cGMP production and NPRA expression and protected allergic mice from airway hyperreactivity and lung inflammation when given either before or after allergen challenge. Leukocyte infiltration was reduced and lung cytokine profiles showed a repolarization from a Th2-like to a Th1-like phenotype. Isatin nanocapsules administered locally to the lung inhibit NPRA signaling but also are capable of lowering the expression of NPRA, thus effectively reducing inflammation in a mouse model of allergic asthma. Pharmacological intervention to reduce NPRA activity through the inflammatory natriuretic peptide axis in the lung may be a useful adjunct therapy for treating lung disease.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Asma
/
Receptores do Fator Natriurético Atrial
/
Isatina
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Int Immunopharmacol
Ano de publicação:
2010
Tipo de documento:
Article