Bradykinin B(1) receptor antagonist R954 inhibits eosinophil activation/proliferation/migration and increases TGF-beta and VEGF in a murine model of asthma


Autoria(s): VASQUEZ-PINTO, Luciana M. C.; NANTEL, Francois; SIROIS, Pierre; JANCAR, Sonia
Contribuinte(s)

UNIVERSIDADE DE SÃO PAULO

Data(s)

20/10/2012

20/10/2012

2010

Resumo

In the present study the effects of bradykinin receptor antagonists were investigated in a murine model of asthma using BALB/c mice immunized with ovalbumin/alum and challenged twice with aerosolized ovalbumin. Twenty four hours later eosinophil proliferation in the bone marrow, activation (lipid bodies formation), migration to lung parenchyma and airways and the contents of the pro-angiogenic and pro-fibrotic cytokines TGF-beta and VEGF were determined. The antagonists of the constitutive B(2) (HOE 140) and inducible B(1) (R954) receptors were administered intraperitoneally 30 min before each challenge. In sensitized mice, the antigen challenge induced eosinophil proliferation in the bone marrow, their migration into the lungs and increased the number of lipid bodies in these cells. These events were reduced by treatment of the mice with the B(1) receptor antagonist. The B(2) antagonist increased the number of eosinophils and lipid bodies in the airways without affecting eosinophil counts in the other compartments. After challenge the airway levels of VEGF and TGF-beta significantly increased and the B(1) receptor antagonist caused a further increase. By immunohistochemistry techniques TGF-beta was found to be expressed in the muscular layer of small blood vessels and VEGF in bronchial epithelial cells. The B(1) receptors were expressed in the endothelial cells. These results showed that in a murine model of asthma the B(1) receptor antagonist has an inhibitory effect on eosinophils in selected compartments and increases the production of cytokines involved in tissue repair. It remains to be determined whether this effects of the B(1) antagonist would modify the progression of the allergic inflammation towards resolution or rather towards fibrosis. (C) 2009 Elsevier Ltd. All rights reserved.

Identificador

NEUROPEPTIDES, v.44, n.2, Special Issue, p.107-113, 2010

0143-4179

http://producao.usp.br/handle/BDPI/28274

10.1016/j.npep.2009.11.001

http://dx.doi.org/10.1016/j.npep.2009.11.001

Idioma(s)

eng

Publicador

CHURCHILL LIVINGSTONE

Relação

Neuropeptides

Direitos

restrictedAccess

Copyright CHURCHILL LIVINGSTONE

Palavras-Chave #TGF-beta #VEGF #Bradykinin #Eosinophils #Asthma #GROWTH-FACTOR-BETA #LUNG INFLAMMATION #GUINEA-PIGS #EXPRESSION #SENSITIZATION #ANGIOGENESIS #ACCUMULATION #MODULATION #RESPONSES #Endocrinology & Metabolism #Neurosciences
Tipo

article

proceedings paper

publishedVersion