Involvement of PKCα-MAPK/ERK-phospholipase A(2) pathway in the Escherichia coli invasion of brain microvascular endothelial cells.
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.
Dept. Scienze Bio-Mediche, University of Catania, Italy.
Mario
M
Salmeri
Carla
C
Motta
Silvana
S
Mastrojeni
Andrea
A
Amodeo
Carmelina Daniela
CD
Anfuso
Giovanni
G
Giurdanella
Angela
A
Morello
Mario
M
Alberghina
Maria Antonietta
MA
Toscano
Gabriella
G
Lupo
D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000098:blood supply*; D002417:Cattle; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism; D003600:Cytosol / Q000201:enzymology; D042783:Endothelial Cells / Q000382:microbiology* / Q000502:physiology; D004730:Endothelium, Vascular / Q000382:microbiology* / Q000502:physiology; D004789:Enzyme Activation; D004926:Escherichia coli / Q000472:pathogenicity*; D020935:MAP Kinase Signaling System; D008565:Membrane Proteins / Q000378:metabolism; D055806:Microvessels / Q000382:microbiology / Q000502:physiology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D054512:Phospholipases A2, Calcium-Independent / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D051571:Protein Kinase C-alpha / Q000378:metabolism*; D034622:RNA Interference
D008565:Membrane Proteins; D051546:Cyclooxygenase 2; D051571:Protein Kinase C-alpha; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D054512:Phospholipases A2, Calcium-Independent