Efeito de ExoU e papel de PAFR na expressão de citocinas relacionadas à inflamação em modelo murino de pneumonia aguda por Pseudomonas aeruginosa

• Autor(a) principal: Flores, Vinícius Ribeiro
• Data de Publicação: 2014
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da UERJ
• Texto Completo: http://www.bdtd.uerj.br/handle/1/14378
• topic: Pseudomonas aeruginosa; ExoU; Cytokines; PAF; Pseudomonas aeruginosa; ExoU; Citocinas; PAF; Pseudomonasaeruginosa; Pulmões Infecções; Toxinas bacterianas Citocinas . 5. Fator de Ativação de Plaquetas Fisiologia. 6. Infecção hospitalar .; Citocinas; Fator de Ativação de Plaquetas Fisiologia; Infecção hospitalar; CNPQ::CIENCIAS BIOLOGICAS::IMUNOLOGIA

The opportunistic Gram-negative bacteria Pseudomonas aeruginosa is an important pathogen in hospital acquired airways infections. ExoU is a bacterial protein injected into host cell cytosol by the type three secretion system that correlates with acute infection severity. The effect of ExoU relies on its phospholipase A2-like activity, which leads to host cell membrane lysis and consequent release of arachidonic acid and lysophospholipids, as well as synthesis of proinflammatory mediators, such as eicosanoids and platelet-activating factor (PAF). ExoU also activates NF-kB, a transcriptional factor that regulates the synthesis of a number of proinflammatory molecules. In the present study, the expression of cytokines involved in inflammatory responses was studied in a murine model of acute pneumonia in which C57/BL6 mice were intratracheally infected with an ExoU-producing P. aeruginosa strain (PA103) or its isogenic mutant ExoU-defective strain (PA103ΔexoU). To assess the role of PAF, mice were treated with the PAF antagonist WEB 2086, or with vehicle, and inoculated with PA103 suspension or saline. After 24 hours, total lung RNA was purified and converted to cDNA for analysis of the expression of same cytokines. Our results showed that mRNA levels of the proinflammatory cytokines IL-1-β, TNFα and IL-6, the antiinflamatory cytokine IL-10 and the recently described cytokine IL-27 were significantly higher in lungs of mice infected with the ExoU-producing strain than in lungs of mice infected with the ExoU-defective mutant. Furthermore, the evaluation of C57/BL6 mice treated with the PAF antagonist WEB 2086 before P. aeruginosa infection revealed that induction of cytokines by ExoU depends on PAFR signaling. These data contributes to the comprehension of the role of ExoU in pathogenesis and confirm the importance of PAF as an important regulator of inflammatory response during pneumonia by ExoU-producing P. aeruginosa strains