Legionella pneumophila-induced PKC, P38 MAPK and NF-kB dependent COX-2 expression in human lung epithelium

Introduction: Legionella pneumophila causes community- and hospital-acquired pneumonia. 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 Legionella pneumophila induced COX-2 dependent PGE2 production in pulmonary epithelial cells.

Methods: A549 cells, Western blot, ELISA, PKC-kinase assay, EMSA

Results: Legionella induced time- and dose-dependently the release of PGE2 in A549 cells as well as the expression of COX-2 but not of COX-1. L. pneumophila induced the degradation of IkBa and subsequent activation of NF-kB-dependent gene transcription. Inhibition of IKK blocked L. pneumophila-induced PGE2 release and COX-2 expression. We noted activation p38 and p42/44 MAP kinase in Legionella-infected A549 cells. Moreover, membrane translocation and activation of PKCalpha was observed in infected cells. PGE2 release and COX-2 expression was reduced by PKC and p38 MAP kinase inhibitors but not by p42/44-inhibitor U0126.

In summary, PKC, p38 MAP kinase and NF-kB controlled COX-2 expression and subsequent PGE2 release by Legionella infected lung epithelial cells, which may significantly contribute to the host response in legionnaires' disease.

The German Federal Ministry of Education and Research, Competence Network CAPNETZ supported this study.