ExoU modulates soluble and membrane-bound ICAM-1 in Pseudomonas aeruginosa-infected endothelial cells.
ExoU, a Pseudomonas aeruginosa cytotoxin injected via the type III secretion system into host cells, possesses eicosanoid-mediated proinflammatory properties due to its phospholipase A(2) (PLA(2)) activity. This report addressed the question whether ExoU may modulate the expression of adhesion molecules in host cells, therefore contributing to the recruitment of leukocyte into infected tissues. ExoU was shown to down-regulate membrane-bound ICAM-1 (mICAM-1) and up-regulate the release of soluble ICAM-1 (sICAM-1) from P. aeruginosa-infected endothelial cells. The modulation of ICAM-1 depended on the direct effect of the ExoU PLA(2) activity and involved the cyclooxygenase (COX) pathway. No differences in mICAM-1 and sICAM-1 mRNA levels were observed when cultures were infected with the ExoU-producing PA103 strain or the mutant PA103DeltaexoU, suggesting that ExoU may proteolytically cleave mICAM-1, producing sICAM-1 in a COX-dependent pathway.
Lins
Renata Ximenes
RX
Departamento de Microbiologia, Imunologia e Parasitologia - FCM/UERJ, Universidade do Estado do Rio de Janeiro, Av. 28 de Setembro, 87 fundos, 3 degrees andar. 20 551-030, Rio de Janeiro, RJ, Brazil.
de Assis
Maria Cristina
MC
Mallet de Lima
Carolina Diettrich
CD
Freitas
Carla
C
Maciel Plotkowski
Maria Cristina
MC
Saliba
Alessandra Mattos
AM
D001426:Bacterial Proteins / Q000378:metabolism*; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism / Q000382:microbiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism / Q000382:microbiology*; D005786:Gene Expression Regulation; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D007956:Leukocidins / Q000378:metabolism*; D008084:Lipoxygenase / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000378:metabolism / Q000472:pathogenicity*
D001426:Bacterial Proteins; D007956:Leukocidins; C510238:Pseudomonas aeruginosa Cytotoxins; C111749:pseudomonas exoprotein A protein, Pseudomonas aeruginosa; D018799:Intercellular Adhesion Molecule-1; D008084:Lipoxygenase; D051546:Cyclooxygenase 2