Vascular Endothelial Growth Factor Receptor 1 Contributes to<i>Escherichia coli</i>K1 Invasion of Human Brain Microvascular Endothelial Cells through the Phosphatidylinositol 3-Kinase/Akt Signaling Pathway

Zhao, Wei; Liu, Wei; Fang, Wen; Kim, Kwang Sik; Chen, Yu Hua

doi:10.1128/iai.00377-10

Cited by 26 publications

(22 citation statements)

References 41 publications

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“…The involvement of VEGFR‐1 has already been shown by Zhao et al . (), which showed the colocalization of VEGFR‐1 with E. coli during bacterial invasion of endothelial cells. In addition, they have shown the association of VEGFR‐1 with the p85 subunit of phosphatidylinositol 3‐kinase (PI3K) in brain microvascular endothelial cells (HBMEC) infected with E. coli and that E. coli ‐triggered PI3K activation in HBMEC was blocked by VEGFR‐1 si RNA and by VEGFR inhibitors.…”

Section: Discussionmentioning

confidence: 95%

“…VEGF‐A, the prototype VEGF ligand, binds and activates two tyrosine kinase receptors: VEGFR‐1 (Flt‐1) and VEGFR‐2 (KDR/Flk‐1). The transmembrane VEGFR‐1 acts as a positive regulator of angiogenesis, inflammatory responses and permeability in several human diseases such as rheumatoid arthritis (Kong et al ., ), cancer (Subramanian et al ., ) and bacterial meningitis with E. coli playing a role in the promotion of the physical association between phosphorylated VEGFR‐1 and p85 subunit of PI3K, highlighting the involvement of VEGFR‐1 in E. coli K1 invasion of microvascular ECs (Zhao et al ., ).…”

Section: Introductionmentioning

confidence: 97%

“…VEGF-A, the prototype VEGF ligand, binds and activates two tyrosine kinase receptors: VEGFR-1 (Flt-1) and VEGFR-2 (KDR/Flk-1). The transmembrane VEGFR-1 acts as a positive regulator of angiogenesis, inflammatory responses and permeability in several human diseases such as rheumatoid arthritis (Kong et al, 2011), cancer (Subramanian et al, 2010) and bacterial meningitis with E. coli playing a role in the promotion of the physical association between phosphorylated VEGFR-1 and p85 subunit of PI3K, highlighting the involvement of VEGFR-1 in E. coli K1 invasion of microvascular ECs (Zhao et al, 2010). High VEGF levels have been measured in the cerebrospinal fluid (CSF) of patients with bacterial meningitis who show severe BBB disruption, and VEGF immunoreactivity was found in endothelium and smooth-muscle cells from brain specimens of patients who died of bacterial meningitis (van der Flier et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

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VEGF receptor-1 involvement in pericyte loss induced byEscherichia coliin anin vitromodel of blood brain barrier

et al. 2013

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SummaryThe key aspect of neonatal meningitis is related to the ability of pathogens to invade the blood-brain barrier (BBB) and to penetrate the central nervous system. In the present study we show that, in an in vitro model of BBB, on the basis of co-culturing primary bovine brain endothelial cells (BBEC) and primary bovine retinal pericytes (BRPC), Escherichia coli infection determines changes of transendothelial electrical resistance (TEER) and permeability (Pe) to sodium fluorescein. In the co-culture model, within BBEC, bacteria are able to stimulate cytosolic and Ca 2+-independent phospholipase A2 (cPLA2 and iPLA2) enzyme activities. In supernatants of E. coli-stimulated co-cultures, an increase in prostaglandins (PGE2) and VEGF production in comparison with untreated cocultures were found. Incubation with E. coli in presence of AACOCF3 or BEL caused a decrease of PGE2 and VEGF release. SEM and TEM images of BBEC and BRPC showed E. coli adhesion to BBEC and BRPC but only in BBEC the invasion occurs. VEGFR-1 but not VEGFR-2 blockade by the specific antibody reduced E. coli invasion in BBEC. In our model of BBB infection, a significant loss of BRPC was observed. Following VEGFR-1, but not VEGFR-2 blockade, or in presence of AACOCF3 or BEL, elevated TEER values, reduced permeability and BRPC loss were found. These data suggest that VEGFR-1 negatively regulates BRPC survival and its blockade protects the barrier integrity. PGs and VEGF could exert a biological effect on BBB, probably by BRPC coverage ablation, thus increasing BBB permeability. Our results show the role played by the BBEC as well as BRPC during a bacterial attack on BBB. A better understanding of the mechanisms by which E. coli enter the nervous system and how bacteria alter the communication between endothelial cells and pericytes may provide exciting new insight for clinical intervention.

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Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

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VEGF receptor-1 involvement in pericyte loss induced byEscherichia coliin anin vitromodel of blood brain barrier

et al. 2013

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“…These include focal adhesion kinase (FAK), paxillin, phosphatidylinositol 3-kinase (PI3K), Src kinase, signal transducers and activators of transcription 3 (STAT3), Rho GTPases (RhoA and Rac1), cytosolic phospholipase A 2 α (cPLA 2 α), 5-lipoxygenase and cysteinyl leukotrienes, epidermal growth factor receptor (EGFR) tyrosine kinase, vascular endothelial growth factor (VEGF) receptor-1, ezrin, radixin and moesin (ERM), calmodulin-dependent myosin light-chain kinase, and protein kinase C (PKC) (7, 21, 40, 41, 52, 55, 68, 86-89) (Figure 2). The host–microbial factors exploiting such host cell signaling molecules for E. coli invasion of the blood-brain barrier, however, remain incompletely elucidated.…”

Section: The Pathognesis Of E Coli Meningitis: Cellular Microbiologymentioning

confidence: 99%

Human Meningitis-Associated Escherichia coli

Kim

2016

EcoSal Plus

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E. coli is the most common Gram-negative bacillary organism causing meningitis and E. coli meningitis continues to be an important cause of mortality and morbidity throughout the world. Our incomplete knowledge of its pathogenesis contributes to such mortality and morbidity. Recent reports of E. coli strains producing CTX-M-type or TEM-type extended-spectrum β-lactamases create a challenge. Studies using in vitro and in vivo models of the blood-brain barrier have shown that E. coli meningitis follows a high-degree of bacteremia and invasion of the blood-brain barrier. E. coli invasion of the blood-brain barrier, the essentials step in the development of E. coli meningitis, requires specific microbial and host factors as well as microbe- and host-specific signaling molecules. Blockade of such microbial and host factors contributing to E. coli invasion of the blood-brain barrier is shown to be efficient in preventing E. coli penetration into the brain. The basis for requiring a high-degree of bacteremia for E. coli penetration of the blood-brain barrier, however, remains unclear. Continued investigation on the microbial and host factors contributing to a high-degree of bacteremia and E. coli invasion of the blood-brain barrier is likely to identify new targets for prevention and therapy of E. coli meningitis.

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“…Isolation of UNG1 complexes using a DNA oligo containing uracil was carried out based on the published protocol by Gerhard Mittler [27]. Briefly, the single-stranded oligonucleotide (5′-CAAAACTGCAGGATGAUTGTGATGAATUTAAGTTAAGU-TAGTTAAGTTAT-3′) was biotinylated at the 5′-end.…”

Section: Isolation Of Ung1 Complexes Using An Uracil-containing Dna Omentioning

confidence: 99%

Hydrogen peroxide mediated mitochondrial UNG1-PRDX3 interaction and UNG1 degradation

Liu

Gong

et al. 2016

Free Radical Biology and Medicine

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Vascular Endothelial Growth Factor Receptor 1 Contributes toEscherichia coliK1 Invasion of Human Brain Microvascular Endothelial Cells through the Phosphatidylinositol 3-Kinase/Akt Signaling Pathway

Cited by 26 publications

References 41 publications

VEGF receptor-1 involvement in pericyte loss induced byEscherichia coliin anin vitromodel of blood brain barrier

VEGF receptor-1 involvement in pericyte loss induced byEscherichia coliin anin vitromodel of blood brain barrier

Human Meningitis-Associated Escherichia coli

Hydrogen peroxide mediated mitochondrial UNG1-PRDX3 interaction and UNG1 degradation

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