In:
American Journal of Physiology-Lung Cellular and Molecular Physiology, American Physiological Society, Vol. 292, No. 1 ( 2007-01), p. L267-L277
Abstract:
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 PGE 2 synthase-1 (mPGES-1)-derived prostaglandins like prostaglandin E 2 (PGE 2 ) are considered as important regulators of lung function. Herein we tested the hypothesis that L. pneumophila induced COX-2 and mPGES-1-dependent PGE 2 production in pulmonary epithelial cells. Legionella induced the release of PGE 2 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 PLA 2 activity in infected cells. Deletion of the type IV secretion system Dot/Icm did not impair Legionella-related COX-2 expression or PGE 2 release in A549 cells. L. pneumophila induced the degradation of IκBα and activated NF-κB. Inhibition of IKK blocked L. pneumophila-induced PGE 2 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 PGE 2 release and COX-2 expression. In summary, PKCα and p38 and p42/44 MAP kinase controlled COX-2 expression and subsequent PGE 2 release by Legionella-infected lung epithelial cells. These pathways may significantly contribute to the host response in Legionnaires' disease.
Type of Medium:
Online Resource
ISSN:
1040-0605
,
1522-1504
DOI:
10.1152/ajplung.00100.2006
Language:
English
Publisher:
American Physiological Society
Publication Date:
2007
detail.hit.zdb_id:
1477300-4
SSG:
12
