Bradykinin inducible receptor is essential to lipopolysaccharide-induced acute lung injury in mice

Bradykinin inducible receptor is essential to lipopolysaccharide-induced acute lung injury in mice

Author Campanholle, Gabriela Google Scholar
Landgraf, Richardt G. Autor UNIFESP Google Scholar
Borducchi, Erica Google Scholar
Semedo, Patricia Autor UNIFESP Google Scholar
Wang, Pamela H. M. Autor UNIFESP Google Scholar
Amano, Mariane T. Google Scholar
Russo, Momtchilo Google Scholar
Pacheco-Silva, Alvaro Autor UNIFESP Google Scholar
Jancar, Sonia Google Scholar
Camara, Niels O. S. Autor UNIFESP Google Scholar
Institution Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
Abstract Lipopolysaccharides from gram-negative bacteria are amongst the most common causative agents of acute lung injury, which is characterized by an inflammatory response, with cellular infiltration and the release of mediators/cytokines. There is evidence that bradykinin plays a role in lung inflammation in asthma but in other types of lung inflammation its role is less clear. in the present study we evaluated the role of the bradykinin B(1) receptor in acute lung injury caused by lipopolysaccharide inhalation and the mechanisms behind bradykinin actions participating in the inflammatory response. We found that in C57BI/6 mice, the bradykinin B(1) receptor expression was up-regulated 24 h after lipopolysaccharide inhalation. At this time, the number of cells and protein concentration were significantly increased in the bronchoalveolar lavage fluid and the mice developed airway hyperreactivity to methacholine. in addition, there was an increased expression of tumor necrosis factor-alpha, interleukin-1 beta and interferon-gamma and chemokines (monocytes chemotactic protein-1 and KC) in the bronchoalveolar lavage fluid and in the lung tissue. We then treated the mice with a bradykinin B, receptor antagonist, R-954 (Ac-Orn-[Oic(2), alpha-MePhe(5), D-beta Nal(7), Ile(8)]desArg(9)-bradykinin), 30 min after lipopolysaccharide administration. We observed that this treatment prevented the airway hyperreactivity as well as the increased cellular infiltration and protein content in the bronchoalveolar lavage fluid. Moreover, R-954 inhibited the expression of cytokines/chemokines. These results implicate bradykinin, acting through B(1) receptor, in the development of acute lung injury caused by lipopolysaccharide inhalation. (C) 2010 Elsevier B.V. All rights reserved.
Keywords Lipopolysaccharide
Bradykinin B(1) receptor
Acute lung injury
Language English
Sponsor Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
INCT Complex Fluids
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Grant number FAPESP: 06/06236-2
FAPESP: 06/03982-5
FAPESP: 07/07139-3
Date 2010-05-25
Published in European Journal of Pharmacology. Amsterdam: Elsevier B.V., v. 634, n. 1-3, p. 132-137, 2010.
ISSN 0014-2999 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 132-137
Access rights Closed access
Type Article
Web of Science ID WOS:000277554900019

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