| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
B-dependent COX-2 expression in human lung epithelium
1 Department of Internal Medicine/Infectious Diseases and Respiratory Medicine, Charite - Universitaetsmedizin Berlin, Berlin, Germany
2 Department of Internal Medicine/Infectious Diseases and Respiratory Medicine, Charite - Universitaetsmedizin Berlin, Berlin, Germany; Institute for Periodontology and Synoptic Dentistry, ChariteCentrum 3 for Dental Medicine, Charite - Universitaetsmedizin Berlin, Berlin, Germany
* To whom correspondence should be addressed. E-mail: Bernd.Schmeck{at}charite.de.
Streptococcus pneumoniae is a major cause of community-acquired pneumonia and death due to infectious diseases in industrialized countries. Lung airway and alveolar epithelial cells comprise an important barrier against airborne pathogens. Cyclooxygenase (COX)-derived prostaglandins like prostaglandin E2 (PGE2) are considered as 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 I
B
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 MAP kinase and cJun-NH2-terminal kinase (JNK) in pneumococci-infected BEAS-2B cells. PGE2 release and COX-2 expression were reduced by p38 MAP kinase-inhibitor SB202190 but not by JNK-inhibitor SP600125. We analyzed interaction of kinase pathways and NF-B activation: dominant negative mutants of p38 MAP kinase isoforms , 
2, 
, and 
blocked S. pneumoniae-induced NF-kB activation. In addition, recruitment of NF-B subunit p65/RelA and RNA polymerase II to the cox2 promoter depended on p38 MAP kinase but not on JNK activity.
In summary, p38 MAP kinase- 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.
This article has been cited by other articles:
|
|
 |
|
  P. D. N'Guessan, F. Riediger, K. Vardarova, S. Scharf, J. Eitel, B. Opitz, H. Slevogt, W. Weichert, A. C. Hocke, B. Schmeck, et al. Statins Control Oxidized LDL-Mediated Histone Modifications and Gene Expression in Cultured Human Endothelial Cells Arterioscler Thromb Vasc Biol, March 1, 2009; 29(3): 380 - 386. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. J. Bootsma, M. Egmont-Petersen, and P. W. M. Hermans Analysis of the In Vitro Transcriptional Response of Human Pharyngeal Epithelial Cells to Adherent Streptococcus pneumoniae: Evidence for a Distinct Response to Encapsulated Strains Infect. Immun., November 1, 2007; 75(11): 5489 - 5499. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. D. N'Guessan, B. Temmesfeld-Wollbruck, J. Zahlten, J. Eitel, S. Zabel, B. Schmeck, B. Opitz, S. Hippenstiel, N. Suttorp, and H. Slevogt Moraxella catarrhalis induces ERK- and NF-{kappa}B-dependent COX-2 and prostaglandin E2 in lung epithelium Eur. Respir. J., September 1, 2007; 30(3): 443 - 451. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. D. N'Guessan, M. O. Etouem, B. Schmeck, A. C. Hocke, S. Scharf, K. Vardarova, B. Opitz, A. Flieger, N. Suttorp, and S. Hippenstiel Legionella pneumophila-induced PKC{alpha}-, MAPK-, and NF-{kappa}B-dependent COX-2 expression in human lung epithelium Am J Physiol Lung Cell Mol Physiol, January 1, 2007; 292(1): L267 - L277. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
