Abstracts (poster) - Wissenschaft Online

Bernd Schmeck, Janina Lorenz, Philippe Dje N'Guessan, Antje Flieger, Vincent van
Laak, Norbert Suttorp, Stefan Hippenstiel
L. pneumophila induce histone modifications in human lung
epithelial cells
Legionella pneumophila causes community- and hospital-acquired pneumonia. Their
effect on histone marks is unknown.
L. pneumophila wildtype strain 130b induced time- and dose-dependently expression of
the important chemoattractant IL-8 and global, genome wide histone modifications in
human lungs epithelial A549 cells. We analyzed the promoter of the important
proinflammatory chemokine IL-8 and found that histone H4 was acetylated and H3 was
phosphorylated at Ser-10 and acetylated at Lys-14, followed by recruitment of
transcription factor NF-κB, and RNA polymerase II as well as gene transcription. L.
pneumophila strain 130b-induced IL-8 expression was decreased by histone
acetyltransferase (HAT) inhibitor anacardic acid and enhanced by the histone
deacetylase (HDAC) inhibitor trichostatin A. Accordingly, after L. pneumophila infection
HATs p300 and CBP were time-dependently recruited to the il8 promoter, whereas
HDAC1 and HDAC5 first vanished and later reappeared at the promoter. Interestingly, L.
pneumophila specifically induced expression of HDAC5 but not of other HDACs in lung
epithelial cells. Furthermore, L. pneumophila-induced cytokine release, promoter specific
histone modifications and Pol-II recruitment were reduced in infection with flagellindeletion
mutants.
In summary, histone acetylation seems to be important for the regulation of
proinflammatory gene expression in L. pneumophila infected lung epithelial cells.
contact:
PD Dr. Bernd Schmeck
Charité - Universitätsmedizin Berlin
Medizinische Klinik m.S. Infektiologie und Pneumologie
Bernd.Schmeck@charite.de
Augustenburger Platz 1
13353 Berlin (Germany)