N'Guessan PD, Etouem MO, Schmeck B, Hocke AC, Scharf S, Vardarova K, Opitz B, Flieger A, Suttorp N, Hippenstiel S (2007): Legionella pneumophila-induced PKCα-, MAPK-, and NF-κB-dependent COX-2 expression in human lung epithelium
Am. J. Physiol. Lung Cell. Mol. Physiol. 292 (1): L267-277, Epub 2006 Sep 29.

Legionella pneumophila causes community- and hospital-acquired pneumonia. Lung airway and alveolar epithelial cells comprise an important barrier against airborne pathogens. Cyclooxygenase (COX) and microsomal PGE₂ synthase-1 (mPGES-1)-derived prostaglandins like prostaglandin E₂ (PGE₂) are considered as important regulators of lung function. Herein we tested the hypothesis that L. pneumophila induced COX-2 and mPGES-1-dependent PGE₂ production in pulmonary epithelial cells. Legionella induced the release of PGE₂ in primary human small airway epithelial cells and A549 cells. This was accompanied by an increased expression of COX-2 and mPGES-1 as well as an increased PLA₂ activity in infected cells. Deletion of the type IV secretion system Dot/Icm did not impair Legionella-related COX-2 expression or PGE₂ release in A549 cells. L. pneumophila induced the degradation of IκBα and activated NF-κB. Inhibition of IKK blocked L. pneumophila-induced PGE₂ release and COX-2 expression. We noted activation of p38 and p42/44 MAP kinase in Legionella-infected A549 cells. Moreover, membrane translocation and activation of PKCα was observed in infected cells. PKCα and p38 and p42/44 MAP kinase inhibitors reduced PGE₂ release and COX-2 expression. In summary, PKCα and p38 and p42/44 MAP kinase controlled COX-2 expression and subsequent PGE₂ release by Legionella-infected lung epithelial cells. These pathways may significantly contribute to the host response in Legionnaires' disease.