Lipid body mobilization in the ExoU-induced release of inflammatory mediators by airway epithelial cells

• Published in: Microbial pathogenesis Vol. 45; no. 1; pp. 30 - 37
• Main Authors: Plotkowski, Maria-Cristina, Brandão, Bruno A., de Assis, Maria-Cristina, Feliciano, Luis-Filipe P., Raymond, Benoit, Freitas, Carla, Saliba, Alessandra M., Zahm, Jean Marie, Touqui, Lhousseine, Bozza, Patrícia T.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier India Pvt Ltd 01.07.2008; Elsevier
• Subjects: Arachidonic Acid; Arachidonic Acid - metabolism; Arachidonic Acids; Arachidonic Acids - pharmacology; Bacterial Proteins; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Bacteriology; Biological and medical sciences; Bronchi; Bronchi - cytology; Bronchi - drug effects; Bronchi - metabolism; Bronchi - microbiology; Cell Line; Cytokines; Cytokines - metabolism; Enzyme Inhibitors; Enzyme Inhibitors - pharmacology; Epithelial Cells; Epithelial Cells - cytology; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Epithelial Cells - microbiology; ExoU; Fundamental and applied biological sciences. Psychology; Human health and pathology; Humans; Inclusion Bodies; Inclusion Bodies - metabolism; Inflammation Mediators; Inflammation Mediators - metabolism; Inflammatory response; Life Sciences; Lipid body; Lipid Metabolism; Microbiology; Miscellaneous; Organophosphonates - pharmacology; PGE2; Phosphonic Acids; Prostaglandins E; Prostaglandins E - metabolism; Pseudomonas aeruginosa; Pseudomonas aeruginosa - drug effects; Pseudomonas aeruginosa - metabolism; Pseudomonas Infections; Pseudomonas Infections - metabolism; Pulmonology and respiratory tract; ExoU; PGE2; Pseudomonas aeruginosa; Inflammatory response; Lipid body; Arachidonic acid; Pseudomonadales; Microbiology; Lipids; Inflammation; Respiratory system; Pseudomonas aeruginosa,ExoU,Lipid body,Inflammatory response,Arachidonic acid,PGE2; Respiratory tract; Bacteria; Pseudomonadaceae; Epithelial cell; Inflammatory cell; Release
• ISSN: 0882-4010; 1096-1208
• DOI: 10.1016/j.micpath.2008.01.008

This report addressed the question whether ExoU stimulation of airway epithelial cells may contribute to the inflammatory response detected in the course of Pseudomonas aeruginosa respiratory infections. Infection with PA103 P. aeruginosa elicited a potent release of IL-6 and IL-8, as well as of arachidonic acid (AA) and PGE 2 that was reduced by the bacterial treatment with MAFP, a cPLA 2 inhibitor. Airway cells from the BEAS-2B line and in primary culture were shown to be enriched in lipid bodies (LBs), that are cytoplasmic domains implicated in AA transformation into eicosanoids. However, cells infected with PA103 and with a mutant deficient in exoU but complemented with a functional gene exhibited reduced contents of LBs, and this reduction was inhibited by MAFP. FACS analysis showed that the decrease in the LB content correlated with the presence of intracellular PGE 2. Also, in PA103-infected cells, PGE 2 was immunolocalized in LBs, suggesting that the reduction in the cell content of the organelles was due to consumption of their glycerolipids, resulting in local synthesis of the prostanoid. In conclusion, we showed the ExoU ability to induce airway epithelial cells to overproduce PGE 2 and we speculate that LB may represent intracellular loci involved in ExoU-induced eicosanoid synthesis.