Linked Life Data

12174085

Source:http://linkedlifedata.com/resource/pubmed/id/12174085

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2002-8-13
pubmed:abstractText
Although epidemiological studies have shown that exposure to tobacco smoking significantly increases the risk of bacterial meningitis, heretofore the pathogenic effects of smoking on this disease have been poorly understood. In order to dissect this issue, we have investigated the effects of nicotine, the major component of tobacco, on E. coli invasion of human brain microvascular endothelial cells (HBMEC). Our studies showed that E. coli invasion of HBMEC was significantly enhanced by nicotine in a dose-dependent manner. The nicotine-mediated enhancement was associated with actin cytoskeleton rearrangement and morphological changes in the eukaryotic host cell that are essential for bacterial entry. The recombinant IbeA protein and alpha-bungarotoxin (a nicotinic acetylcholine receptor antagonist) were able to efficiently block the nicotine-mediated cellular effects, suggesting the involvement of the IbeA and nicotinic receptors. Blocking of phosphatidylinositol 3-kinase (PI3K) by LY294002 abolished the entry of E. coli in HBMECs treated with nicotine in a dose-dependent manner. Inhibition of PI3K was associated with decreased phosphorylation of Akt and actin cytoskeletal rearrangement. In contrast to PI3K, blockage of Rho kinase (ROCK) by Y27632 upregulated both nicotine- and E. coli-mediated cellular responses. Thus, this study provides experimental evidence for the first time that the major component of tobacco, nicotine, enhances meningitic E. coli invasion of HBMEC through modulation of cytoskeleton.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Actin Depolymerizing Factors, http://linkedlifedata.com/resource/pubmed/chemical/Actins, http://linkedlifedata.com/resource/pubmed/chemical/Bungarotoxins, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Escherichia coli Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Ibe10 protein, E coli, http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides..., http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Microfilament Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Nicotine, http://linkedlifedata.com/resource/pubmed/chemical/Nicotinic Agonists, http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Nicotinic, http://linkedlifedata.com/resource/pubmed/chemical/rho-Associated Kinases
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1462-5814
pubmed:author
pubmed:issnType
Print
pubmed:volume
4
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
503-14
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:12174085-Actin Cytoskeleton, pubmed-meshheading:12174085-Actin Depolymerizing Factors, pubmed-meshheading:12174085-Actins, pubmed-meshheading:12174085-Blood-Brain Barrier, pubmed-meshheading:12174085-Brain, pubmed-meshheading:12174085-Bungarotoxins, pubmed-meshheading:12174085-Cells, Cultured, pubmed-meshheading:12174085-Endothelium, Vascular, pubmed-meshheading:12174085-Enzyme Inhibitors, pubmed-meshheading:12174085-Escherichia coli, pubmed-meshheading:12174085-Escherichia coli Proteins, pubmed-meshheading:12174085-Humans, pubmed-meshheading:12174085-Intracellular Signaling Peptides and Proteins, pubmed-meshheading:12174085-Membrane Proteins, pubmed-meshheading:12174085-Microfilament Proteins, pubmed-meshheading:12174085-Nicotine, pubmed-meshheading:12174085-Nicotinic Agonists, pubmed-meshheading:12174085-Phosphatidylinositol 3-Kinases, pubmed-meshheading:12174085-Protein-Serine-Threonine Kinases, pubmed-meshheading:12174085-Receptors, Cell Surface, pubmed-meshheading:12174085-Receptors, Nicotinic, pubmed-meshheading:12174085-rho-Associated Kinases
pubmed:year
2002
pubmed:articleTitle
Enhanced Escherichia coli invasion of human brain microvascular endothelial cells is associated with alternations in cytoskeleton induced by nicotine.
pubmed:affiliation
Childrens Hospital Los Angeles, University of Southern California, Los Angeles, CA 90027, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't