Autor: |
Coutinho DS; Laboratório de Inflamação, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil., Anjos-Valotta EA; Universidade Estadual da Zona Oeste, Rio de Janeiro, Brazil., do Nascimento CVMF; Laboratório de Inflamação, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil., Pires ALA; Laboratório de Inflamação, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil., Napimoga MH; Laboratory of Immunology and Molecular Biology, São Leopoldo Mandic Institute and Research Center, Campinas, Brazil., Carvalho VF; Laboratório de Inflamação, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil., Torres RC; Laboratório de Inflamação, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil., E Silva PMR; Laboratório de Inflamação, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil., Martins MA; Laboratório de Inflamação, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. |
Abstrakt: |
15-deoxy-Δ-12,14-prostaglandin J 2 (15d-PGJ 2 ) 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-PGJ 2 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-PGJ 2 were assessed. 15d-PGJ 2 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-PGJ 2 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-PGJ 2 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-PGJ 2 was found effective in inhibiting NF-κB phosphorylation upon HDM challenge as measured by Western blotting. In conclusion, our findings suggest that 15d-PGJ 2 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. |