ExoU-induced redox imbalance and oxidative stress in airway epithelial cells during Pseudomonas aeruginosa pneumosepsis.

Autor: da Cunha LG Jr; Departamento de Microbiologia, Imunologia e Parasitologia, Universidade do Estado do Rio de Janeiro, Av. 28 de Setembro, 87, Fundos, 3° andar, Vila Isabel, Rio de Janeiro, RJ, 20.551-030, Brazil., Ferreira MF; Departamento de Microbiologia, Imunologia e Parasitologia, Universidade do Estado do Rio de Janeiro, Av. 28 de Setembro, 87, Fundos, 3° andar, Vila Isabel, Rio de Janeiro, RJ, 20.551-030, Brazil., de Moraes JA; Laboratório de Farmacologia Celular e Molecular, Departamento de Biologia Celular, IBRAG, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brazil., Reis PA; Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil., Castro-Faria-Neto HC; Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil., Barja-Fidalgo C; Laboratório de Farmacologia Celular e Molecular, Departamento de Biologia Celular, IBRAG, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brazil., Plotkowski MC; Departamento de Microbiologia, Imunologia e Parasitologia, Universidade do Estado do Rio de Janeiro, Av. 28 de Setembro, 87, Fundos, 3° andar, Vila Isabel, Rio de Janeiro, RJ, 20.551-030, Brazil., Saliba AM; Departamento de Microbiologia, Imunologia e Parasitologia, Universidade do Estado do Rio de Janeiro, Av. 28 de Setembro, 87, Fundos, 3° andar, Vila Isabel, Rio de Janeiro, RJ, 20.551-030, Brazil. alessandrasaliba@hotmail.com.
Jazyk: angličtina
Zdroj: Medical microbiology and immunology [Med Microbiol Immunol] 2015 Dec; Vol. 204 (6), pp. 673-80. Date of Electronic Publication: 2015 Apr 23.
DOI: 10.1007/s00430-015-0418-x
Abstrakt: ExoU is a potent proinflammatory toxin produced by Pseudomonas aeruginosa, a major agent of severe lung infection and sepsis. Because inflammation is usually associated with oxidative stress, we investigated the effect of ExoU on free radical production and antioxidant defense mechanisms during the course of P. aeruginosa infection. In an experimental model of acute pneumonia, ExoU accounted for increased lipid peroxidation in mice lungs as soon as 3 h after intratracheal instillation of PA103 P. aeruginosa strain. The contribution of airway cells to the generation of a redox imbalance was assessed by in vitro tests carried out with A549 airway epithelial cells. Cultures infected with the ExoU-producing PA103 P. aeruginosa strain produced significantly increased concentrations of lipid hydroperoxides, 8-isoprostane, reactive oxygen intermediates, peroxynitrite and nitric oxide (NO), when compared to cells infected with exoU-deficient mutants. Overproduction of NO by PA103-infected cells likely resulted from overexpression of both inducible and endothelial NO synthase isoforms. PA103 infection was also associated with a significantly increased activity of superoxide dismutase (SOD) and decreased levels of reduced glutathione (GSH), a major antioxidant compound. Our findings unveil another potential mechanism of tissue damage during infection by ExoU-producing P. aeruginosa strains.
Databáze: MEDLINE
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