Eicosanoid-mediated proinflammatory activity of Pseudomonas aeruginosa ExoU
As Pseudomonas aeruginosa ExoU possesses two functional blocks of homology to calcium-independent (iPLA(2)) and cytosolic phospholipase A(2) (cPLA(2)), we addressed the question whether it would exhibit a proinflammatory activity by enhancing the synthesis of eicosanoids by host organisms. Endothelial cells from the HMEC-1 line infected with the ExoU-producing PA103 strain exhibited a potent release of arachidonic acid (AA) that could be significantly inhibited by methyl arachidonyl fluorophosphonate (MAFP), a specific PLA(2) inhibitor, as well as significant amounts of the cyclooxygenase (COX)-derived prostaglandins PGE(2) and PGI(2). Cells infected with an isogenic mutant defective in ExoU synthesis did not differ from non-infected cells in the AA release and produced prostanoids in significantly lower concentrations. Infection by PA103 induced a marked inflammatory response in two different in vivo experimental models. Inoculation of the parental bacteria into mice footpads led to an early increase in the infected limb volume that could be significantly reduced by inhibitors of both COX and lipoxygenase (ibuprofen and NDGA respectively). In an experimental respiratory infection model, bronchoalveolar lavage (BAL) from mice instilled with 10(4) cfu of PA103 exhibited a marked influx of inflammatory cells and PGE(2) release that could be significantly reduced by indomethacin, a non-selective COX inhibitor. Our results suggest that ExoU may contribute to P. aeruginosa pathogenesis by inducing an eicosanoid-mediated inflammatory response of host organisms.
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2005 |
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| Erschienen: |
2005 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:7 |
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| Enthalten in: |
Cellular microbiology - 7(2005), 12 vom: 01. Dez., Seite 1811-22 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Saliba, A M [VerfasserIn] |
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| Anmerkungen: |
Date Completed 12.01.2006 Date Revised 24.11.2016 published: Print Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM159138523 |
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| 100 | 1 | |a Saliba, A M |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Eicosanoid-mediated proinflammatory activity of Pseudomonas aeruginosa ExoU |
| 264 | 1 | |c 2005 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
| 338 | |a Band |b nc |2 rdacarrier | ||
| 500 | |a Date Completed 12.01.2006 | ||
| 500 | |a Date Revised 24.11.2016 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a As Pseudomonas aeruginosa ExoU possesses two functional blocks of homology to calcium-independent (iPLA(2)) and cytosolic phospholipase A(2) (cPLA(2)), we addressed the question whether it would exhibit a proinflammatory activity by enhancing the synthesis of eicosanoids by host organisms. Endothelial cells from the HMEC-1 line infected with the ExoU-producing PA103 strain exhibited a potent release of arachidonic acid (AA) that could be significantly inhibited by methyl arachidonyl fluorophosphonate (MAFP), a specific PLA(2) inhibitor, as well as significant amounts of the cyclooxygenase (COX)-derived prostaglandins PGE(2) and PGI(2). Cells infected with an isogenic mutant defective in ExoU synthesis did not differ from non-infected cells in the AA release and produced prostanoids in significantly lower concentrations. Infection by PA103 induced a marked inflammatory response in two different in vivo experimental models. Inoculation of the parental bacteria into mice footpads led to an early increase in the infected limb volume that could be significantly reduced by inhibitors of both COX and lipoxygenase (ibuprofen and NDGA respectively). In an experimental respiratory infection model, bronchoalveolar lavage (BAL) from mice instilled with 10(4) cfu of PA103 exhibited a marked influx of inflammatory cells and PGE(2) release that could be significantly reduced by indomethacin, a non-selective COX inhibitor. Our results suggest that ExoU may contribute to P. aeruginosa pathogenesis by inducing an eicosanoid-mediated inflammatory response of host organisms | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Anti-Inflammatory Agents, Non-Steroidal |2 NLM | |
| 650 | 7 | |a Arachidonic Acids |2 NLM | |
| 650 | 7 | |a Bacterial Proteins |2 NLM | |
| 650 | 7 | |a Bacterial Toxins |2 NLM | |
| 650 | 7 | |a Eicosanoids |2 NLM | |
| 650 | 7 | |a Lipoxygenase Inhibitors |2 NLM | |
| 650 | 7 | |a Organophosphonates |2 NLM | |
| 650 | 7 | |a methyl arachidonylfluorophosphonate |2 NLM | |
| 650 | 7 | |a pseudomonas exoprotein A protein, Pseudomonas aeruginosa |2 NLM | |
| 650 | 7 | |a Arachidonic Acid |2 NLM | |
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| 650 | 7 | |a Masoprocol |2 NLM | |
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| 650 | 7 | |a Epoprostenol |2 NLM | |
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| 650 | 7 | |a Phospholipases A |2 NLM | |
| 650 | 7 | |a EC 3.1.1.32 |2 NLM | |
| 650 | 7 | |a Group IV Phospholipases A2 |2 NLM | |
| 650 | 7 | |a EC 3.1.1.4 |2 NLM | |
| 650 | 7 | |a Dinoprostone |2 NLM | |
| 650 | 7 | |a K7Q1JQR04M |2 NLM | |
| 650 | 7 | |a Ibuprofen |2 NLM | |
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| 650 | 7 | |a Indomethacin |2 NLM | |
| 650 | 7 | |a XXE1CET956 |2 NLM | |
| 700 | 1 | |a Nascimento, D O |e verfasserin |4 aut | |
| 700 | 1 | |a Silva, M C A |e verfasserin |4 aut | |
| 700 | 1 | |a Assis, M C |e verfasserin |4 aut | |
| 700 | 1 | |a Gayer, C R M |e verfasserin |4 aut | |
| 700 | 1 | |a Raymond, B |e verfasserin |4 aut | |
| 700 | 1 | |a Coelho, M G P |e verfasserin |4 aut | |
| 700 | 1 | |a Marques, E A |e verfasserin |4 aut | |
| 700 | 1 | |a Touqui, L |e verfasserin |4 aut | |
| 700 | 1 | |a Albano, R M |e verfasserin |4 aut | |
| 700 | 1 | |a Lopes, U G |e verfasserin |4 aut | |
| 700 | 1 | |a Paiva, D D |e verfasserin |4 aut | |
| 700 | 1 | |a Bozza, P T |e verfasserin |4 aut | |
| 700 | 1 | |a Plotkowski, M C |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Cellular microbiology |d 1999 |g 7(2005), 12 vom: 01. Dez., Seite 1811-22 |w (DE-627)NLM111193869 |x 1462-5822 |7 nnns |
| 773 | 1 | 8 | |g volume:7 |g year:2005 |g number:12 |g day:01 |g month:12 |g pages:1811-22 |
| 912 | |a GBV_USEFLAG_A | ||
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