Moraxella catarrhalis induces ERK- and NF-kappaB-dependent COX-2 and prostaglandin E2 in lung epithelium.
Moraxella catarrhalis is a major cause of infectious exacerbations of chronic obstructive lung disease. Cyclooxygenase (COX)-derived prostaglandins, such as prostaglandin E(2) (PGE(2)), are considered to be important regulators of lung function. The present authors tested the hypothesis that M. catarrhalis induces COX-2-dependent PGE(2) production in pulmonary epithelial cells. In the present study, the authors demonstrate that M. catarrhalis specifically induces COX-2 expression and subsequent PGE(2) release in pulmonary epithelial cells. Furthermore, the prostanoid receptor subtypes EP2 and EP4 were also upregulated in these cells. The M. catarrhalis-specific ubiquitous cell surface protein A1 was important for the induction of COX-2 and PGE(2). Moreover, M. catarrhalis-induced COX-2 and PGE(2) expression was dependent on extracellular signal-regulated kinase 1/2-driven activation of nuclear factor-kappaB, but not on the activation of p38 mitogen-activated protein kinase. In conclusion, the present data suggest that ubiquitous cell surface protein A1 of Moraxella catarrhalis, extracellular signal-regulated kinase 1/2 and nuclear factor-kappaB control cyclooxygenase-2 expression and subsequent prostaglandin E(2) release by lung epithelial cells. Moraxella catarrhalis-induced prostaglandin E(2) expression might counteract lung inflammation promoting colonisation of the respiratory tract in chronic obstructive pulmonary disease patients.
N'Guessan
P D
PD
Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
Temmesfeld-Wollbrück
B
B
Zahlten
J
J
Eitel
J
J
Zabel
S
S
Schmeck
B
B
Opitz
B
B
Hippenstiel
S
S
Suttorp
N
N
Slevogt
H
H
D001425:Bacterial Outer Membrane Proteins / Q000276:immunology; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism*; D004790:Enzyme Induction / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D008168:Lung / Q000276:immunology*; D008565:Membrane Proteins / Q000276:immunology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D001936:Moraxella catarrhalis / Q000276:immunology*; D016328:NF-kappa B / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000276:immunology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology
D001425:Bacterial Outer Membrane Proteins; D008565:Membrane Proteins; D016328:NF-kappa B; C089675:UspA protein, Moraxella catarrhalis; D051546:Cyclooxygenase 2; D048049:Extracellular Signal-Regulated MAP Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D015232:Dinoprostone