Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/327315
Type: Artigo
Title: The Soluble Guanylyl Cyclase Activator Bay 60-2770 Inhibits Murine Allergic Airways Inflammation And Human Eosinophil Chemotaxis
Author: Baldissera
Lineu
Jr.; Squebola-Cola
Dalize M.; Calixto
Marina C.; Lima-Barbosa
Ana P.; Renno
Andre L.; Anhe
Gabriel F.; Condino-Neto
Antonio; De Nucci
Gilberto; Antunes
Edson
Abstract: Activators of soluble guanylyl cyclase (sGC) act preferentially in conditions of enzyme oxidation or haem group removal. This study was designed to investigate the effects of the sGC activator BAY 60-2770 in murine airways inflammation and human eosinophil chemotaxis. Methods: C57BI/6 mice treated or not with BAY 60-2770 (1 mg/kg/day, 14 days) were intranasally challenged with ovalbumin (OVA). At 48 h, bronchoalveolar lavage fluid (BALF) was performed, and circulating blood, bone marrow and lungs were obtained. Human eosinophils purified from peripheral blood were used to evaluate the cell chemotaxis. Results: OVA-challenge promoted marked increases in eosinophil number in BAL, lung tissue, circulating blood and bone marrow, all of which were significantly reduced by BAY 60-2770. The IL-4 and IL-5 levels in BALF were significantly reduced by BAY 60-2770. Increased protein expression of iNOS, along with decreases of expression of sGC (alpha 1 and beta 1 subunits) and cGMP levels were detected in lung tissue of OVA-challenged mice. BAY 60-2770 fully restored to baseline the iNOS and sGC subunit expressions, and cGMP levels. In human isolated eosinophils, BAY 60-2770 (1-5 mu M) had no effects on the cGMP levels and eotaxin-induced chemotaxis; however, prior incubation with ODQ (10 mu M) markedly elevated the BAY 60-2770-induced cyclic GMP production, further inhibiting the eosinophil chemotaxis. Conclusions: BAY 60-2770 reduces airway eosinophilic inflammation and rescue the sGC levels. In human eosinophils under oxidized conditions, BAY 60-2770 elevates the cGMP levels causing cell chemotaxis inhibition. BAY 60-2770 may reveal a novel therapeutic target for asthma treatment. (C) 2016 Elsevier Ltd. All rights reserved.
Subject: Th2 Cytokines
Bone Marrow
Eotaxin
Cyclic Gmp
Inducible Nitric Oxide Synthase
Editor: Academic Press Ltd- Elsevier Science Ltd
London
Rights: fechado
Identifier DOI: 10.1016/j.pupt.2016.11.001
Address: http://www-sciencedirect-com.ez88.periodicos.capes.gov.br/science/article/pii/S1094553916301456?via%3Dihub
Date Issue: 2016
Appears in Collections:Unicamp - Artigos e Outros Documentos

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