Abstract
Escherichia coli K1 is the most common Gram-negative organism that causes neonatal meningitis following penetration of the blood-brain barrier. In the present study we demonstrated the involvement of cytosolic (cPLA(2)) and calcium-independent phospholipase A(2) (iPLA(2)) and the contribution of cyclooxygenase-2 products in E. coli invasion of microvascular endothelial cells. The traversal of bacteria did not determine trans-endothelial electrical resistance (TEER) and ZO-1 expression changes and was reduced by PLA(2)s siRNA. cPLA(2) and iPLA(2) enzyme activities and cPLA(2) phosphorylation were stimulated after E. coli incubation and were attenuated by PLA(2), PI3-K, ERK 1/2 inhibitors. Our results demonstrate the role of PKCα/ERK/MAPK signaling pathways in governing the E. coli penetration into the brain.
Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Blood-Brain Barrier
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Brain / blood supply*
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Cattle
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Cells, Cultured
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Cyclooxygenase 2 / metabolism
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Cytosol / enzymology
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Endothelial Cells / microbiology*
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Endothelial Cells / physiology
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Endothelium, Vascular / microbiology*
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Endothelium, Vascular / physiology
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Enzyme Activation
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Escherichia coli / pathogenicity*
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MAP Kinase Signaling System*
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Membrane Proteins / metabolism
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Microvessels / microbiology
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Microvessels / physiology
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3 / metabolism
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Phospholipases A2, Calcium-Independent / antagonists & inhibitors
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Phospholipases A2, Calcium-Independent / genetics
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Phospholipases A2, Calcium-Independent / metabolism*
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Phosphorylation
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Protein Kinase C-alpha / metabolism*
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RNA Interference
Substances
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Membrane Proteins
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Cyclooxygenase 2
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Protein Kinase C-alpha
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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Phospholipases A2, Calcium-Independent