Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/23111
Title: 15-Deoxy-Delta-12,14-Prostaglandin J2 Inhibits Lung Inflammation and Remodeling in Distinct Murine Models of Asthma
Authors: Coutinho, Diego S.
Anjos-Valotta, Edna A.
Nascimento, Caio V. M. F. do
Pires, Ana Lucia A.
Napimoga, Marcelo H.
Carvalho, Vinícius F.
Torres, Rafael C.
Silva, Patrícia M. R. e
Martins, Marco A.
Affilliation: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ. Brasil.
Universidade Estadual da Zona Oeste. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ. Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ. Brasil.
Instituto e Centro de Pesquisa São Leopoldo Mandic. Campinas, SP, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ. Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ. Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ. Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ. Brasil.
Abstract: 15-deoxy-Δ-12,14-prostaglandin J2 (15d-PGJ2) has been described as an anti-inflammatory lipid mediator in several in vitro and in vivo studies, but its effect on allergic pulmonary inflammation remains elusive. The aim of this study was to investigate the therapeutic potential of 15d-PGJ2 based on distinct murine models of allergic asthma triggered by either ovalbumin (OVA) or house dust mite extract (HDM). Characteristics of lung inflammation, airway hyper-reactivity (AHR), mucus exacerbation, and lung remodeling in sensitized A/J mice treated or not with 15d-PGJ2 were assessed. 15d-PGJ2 treatments were carried out systemically or topically given via subcutaneous injection or intranasal instillation, respectively. Analyses were carried out 24 h after the last allergen provocation. Irrespective of the route of administration, 15d-PGJ2 significantly inhibited the peribronchial accumulation of eosinophils and neutrophils, subepithelial fibrosis and also mucus exacerbation caused by either OVA or HDM challenge. The protective effect of 15d-PGJ2 occurred in parallel with inhibition of allergen-induced AHR and lung tissue production of pro-inflammatory cytokines, such as interleukin (IL)-5, IL-13, IL-17, and TNF-α. Finally, 15d-PGJ2 was found effective in inhibiting NF-κB phosphorylation upon HDM challenge as measured by Western blotting. In conclusion, our findings suggest that 15d-PGJ2 can reduce crucial features of asthma, including AHR, lung inflammation, and remodeling in distinct murine models of the disease. These effects are associated with a decrease in lung tissue generation of pro-inflammatory cytokines by a mechanism related to downregulation of NF-κB phosphorylation.
Keywords: asthma
house dust mite
allergen
15d-PGJ
lung inflammation
resolution
keywords: Asma
Inflamação pulmonar
Alérgenos
Pyroglyphidae
Negociação
Issue Date: 2017
Publisher: Frontiers Media
Citation: COUTINHO, Diego S. et al. 15-Deoxy-Delta-12,14-Prostaglandin J2 inhibits lung inflammation and remodeling in Distinct Murine Models of asthma. Frontiers in Immunology, v.8, Article 140, 13p, June 2017.
DOI: 10.3389/fimmu.2017.00740
ISSN: 1664-3224
Copyright: open access
Appears in Collections:IOC - Artigos de Periódicos

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