Efeito de ExoU na ativação de NF-κB e na secreção de IL-8 por células humanas infectadas por Pseudomonas aeruginosa

• Autor(a) principal: Lima, Carolina Diettrich Mallet de
• Data de Publicação: 2011
• 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/1/14398
• topic: Pseudomonas aeruginosa; ExoU; Type III Secretion System; Inflammation; NF-Κ; Interleukin 8; Pseudomonas aeruginosa; ExoU; Sistema de secreção do tipo III; Inflamação; NF-κ; Interleucina 8; CNPQ::CIENCIAS BIOLOGICAS::MICROBIOLOGIA::MICROBIOLOGIA APLICADA::MICROBIOLOGIA MEDICA

ExoU, a cytotoxin produced by the opportunistic pathogen Pseudomonas aeruginosa that is translocated into host cell cytosol by the type three secretory system, has been associated with severity of acute infections. We have previously described the potent ExoU proinflammatory activity, which accounts for a market recruitment of neutrophils to infected tissues. In this present study, the effect of ExoU on the activation of the transcriptional factor NF-B and on the regulation of the expression and secretion of the chemokine IL-8 was investigated in human epithelial respiratory and endothelial cell cultures infected with the ExoU-producing PA103 P. aeruginosa or with the bacterial mutant with the deletion of the exoU gene PA103exoU. By semi-quantitative RT-PCR, ExoU was shown to significantly increase the expression of IL-8 mRNA. By electrophoretic mobility shift assay (EMSA), supershift and reporter assay ExoU was shown to induce the nuclear translocation of the NF-κB p65/p50 transactivator heterodimer as well as the NF-κB-dependent transcriptional activity. In addition, treatment both the IL-8 mRNA expression and the protein secretion. Together, our results show that ExoU activates NF-B and stimulates IL-8 expression and secretion by P. aeruginosa-infected human epithelial respiratory and endothelial cells