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This Article Full Text Full Text (PDF) All Versions of this Article: 290/6/L1131    most recent 00383.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (10) Citing Articles via Google Scholar Google Scholar Articles by N’Guessan, P. D. Articles by Schmeck, B. Search for Related Content PubMed PubMed Citation Articles by N’Guessan, P. D. Articles by Schmeck, B.

Streptococcus pneumoniae induced p38 MAPK- and NF-B-dependent COX-2 expression in human lung epithelium

¹Department of Internal Medicine/Infectious Diseases and Respiratory Medicine, and ²Institute for Periodontology and Synoptic Dentistry, Charité Centrum 3 for Dental Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany

Submitted 6 September 2005 ; accepted in final form 9 January 2006

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 PGE₂, are considered to be important regulators of lung function. Herein, we tested the hypothesis that pneumococci induced COX-2-dependent PGE₂ production in pulmonary epithelial cells. Pneumococci-infected human pulmonary epithelial BEAS-2B cells released PGE₂. 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 IB and DNA binding of NF-B. A specific peptide inhibitor of the IB kinase complex blocked pneumococci-induced PGE₂ release and COX-2 expression. In addition, we noted activation of p38 MAPK and JNK in pneumococci-infected BEAS-2B cells. PGE₂ 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-B activation: dominant-negative mutants of p38 MAPK isoforms , ₂, , and blocked S. pneumoniae-induced NF-B activation. In addition, recruitment of NF-B 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-B-controlled COX-2 expression and subsequent PGE₂ release by lung epithelial cells may contribute significantly to the host response in pneumococcal pneumonia.

cyclooxygenase-2; p38 mitogen-activated protein kinase; nuclear factor-B

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