Visit our Expo - Redox and Inflammation signaling 2012

VIII. Inflammation specific signaling Poster VIII, 22
Streptococcus pneumoniae-induced p38 MAPK and NF-kappaB dependent COX-2
expression in human lung epithelium
P. Dje N´Guessan, S. Hippenstiel, M. O. Etouem, J. Zahlten, W. Beermann, D. Lindner,
B. Opitz, M. Witzenrath, S. Rosseau, N. Suttorp, B. Schmeck
Department of Internal Medicine/Infectious Diseases, Charité – Universitätsmedizin
Berlin, 13353 Berlin, E-mail: Stefan.hippenstiel@charite.de
S. pneumoniae is a major cause of community-acquired pneumonia and death due to
infectious diseases in industrialized countries. 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 IkappaBalpha and DNAbinding
of NF-kappaB. Specific inhibition of the IKK kinase complex blocked pneumococciinduced
PGE2 release and COX-2 expression. p38 MAP kinase and cJun-NH2-terminal
kinase (JNK) were activated in pneumococci infected cells. PGE2 release and COX-2
expression was reduced by p38 MAP kinase-inhibion but not by JNK-inhibition. Dominant
negative mutants of p38 MAP kinase isoforms alpha, beta2, gamma, and delta blocked S.
pneumoniae-induced NF-kaapB activation. In addition, recruitment of NF-kappaB 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-kappaB controlled COX-2 expression
and subsequent PGE2 release by lung epithelial cells may contribute significantly to the host
response in pneumococcal pneumonia.
Supported by German Federal Ministry of Education and Research, Competence Network
CAPNETZ.
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