Linked Life Data

16414978

Source:http://linkedlifedata.com/resource/pubmed/id/16414978

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2006-5-10
pubmed:abstractText
Streptococcus pneumoniae is a major cause of community-acquired pneumonia and death from infectious diseases in industrialized countries. Lung airway and alveolar epithelial cells comprise an important barrier against airborne pathogens. Cyclooxygenase (COX)-derived prostaglandins, such as PGE(2), are considered to be important regulators of lung function. Herein, we tested the hypothesis that pneumococci induced COX-2-dependent PGE(2) production in pulmonary epithelial cells. Pneumococci-infected human pulmonary epithelial BEAS-2B cells released PGE(2). Expression of COX-2 but not COX-1 was dose and time dependently increased in S. pneumoniae-infected BEAS-2B cells as well as in lungs of mice with pneumococcal pneumonia. S. pneumoniae induced degradation of IkappaBalpha and DNA binding of NF-kappaB. A specific peptide inhibitor of the IkappaBalpha kinase complex blocked pneumococci-induced PGE(2) release and COX-2 expression. In addition, we noted activation of p38 MAPK and JNK in pneumococci-infected BEAS-2B cells. PGE(2) release and COX-2 expression were reduced by p38 MAPK inhibitor SB-202190 but not by JNK inhibitor SP-600125. We analyzed interaction of kinase pathways and NF-kappaB activation: dominant-negative mutants of p38 MAPK isoforms alpha, beta(2), gamma, and delta blocked S. pneumoniae-induced NF-kappaB activation. In addition, recruitment of NF-kappaB subunit p65/RelA and RNA polymerase II to the cox2 promoter depended on p38 MAPK but not on JNK activity. In summary, p38 MAPK- and NF-kappaB-controlled COX-2 expression and subsequent PGE(2) release by lung epithelial cells may contribute significantly to the host response in pneumococcal pneumonia.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1040-0605
pubmed:author
pubmed:issnType
Print
pubmed:volume
290
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
L1131-8
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:16414978-Base Sequence, pubmed-meshheading:16414978-Cell Line, pubmed-meshheading:16414978-Cyclooxygenase 2, pubmed-meshheading:16414978-DNA Primers, pubmed-meshheading:16414978-Enzyme Induction, pubmed-meshheading:16414978-Enzyme Inhibitors, pubmed-meshheading:16414978-Gene Expression Regulation, Bacterial, pubmed-meshheading:16414978-Gene Expression Regulation, Enzymologic, pubmed-meshheading:16414978-Humans, pubmed-meshheading:16414978-Imidazoles, pubmed-meshheading:16414978-Lung, pubmed-meshheading:16414978-NF-kappa B, pubmed-meshheading:16414978-Plasmids, pubmed-meshheading:16414978-Pneumococcal Infections, pubmed-meshheading:16414978-Pyridines, pubmed-meshheading:16414978-Respiratory Mucosa, pubmed-meshheading:16414978-Streptococcus pneumoniae, pubmed-meshheading:16414978-Transfection, pubmed-meshheading:16414978-p38 Mitogen-Activated Protein Kinases
pubmed:year
2006
pubmed:articleTitle
Streptococcus pneumoniae induced p38 MAPK- and NF-kappaB-dependent COX-2 expression in human lung epithelium.
pubmed:affiliation
Dept. of Internal Medicine/Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't