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

• Published in: American journal of physiology. Lung cellular and molecular physiology 2006-06, Vol.290 (6), p.L1131-L1138
• Main Authors: N’Guessan, Philippe Dje, Hippenstiel, Stefan, Etouem, Mirabelle O., Zahlten, Janine, Beermann, Wiebke, Lindner, David, Opitz, Bastian, Witzenrath, Martin, Rosseau, Simone, Suttorp, Norbert, Schmeck, Bernd
• Format: Article
• Language: English
• Subjects: Streptococcus pneumoniae
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.00383.2005

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 IκBα and DNA binding of NF-κB. A specific peptide inhibitor of the IκBα 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-κB activation: dominant-negative mutants of p38 MAPK isoforms α, β 2 , γ, and δ blocked S. pneumoniae-induced NF-κB activation. In addition, recruitment of NF-κB 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-κB-controlled COX-2 expression and subsequent PGE 2 release by lung epithelial cells may contribute significantly to the host response in pneumococcal pneumonia.