Moraxella catarrhalisinduces ERK- and NF-κB-dependent COX-2 and prostaglandin E₂in lung epithelium

Abstract

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-kB, 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-kB 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.

Overexpression of farnesoid X receptor in small airways contributes to epithelial to mesenchymal transition and COX-2 expression in chronic obstructive pulmonary disease

“…Accumulating evidences suggest that airway epithelial cells can participate in persistent airway inflammation via the secretion of multiple inflammatory mediators, such as COX-2, in response to Cigarette smoke and other irritants. COX-2 is the main contributor to the production of pro-inflammatory prostanoids in airway inflammation and other inflammatory diseases (7,9,33). Similar to previous reports (6,7), our data also demonstrated the overexpression of COX-2 in small airways of COPD lungs.…”

“…The levels of COX-2 and PGE 2 are significantly increased in COPD lungs, and the expression of PGE2 is associated with the severity of airflow limitation (6)(7)(8). Several types of lung cells, including airway epithelial cells and lung fibroblasts, are capable of producing COX-2 in response to toxic irritators such as cigarette smoke, bile acid aspiration and bacterial infection (9)(10)(11). Moreover, inhibition of COX-2 or COX-2-induced PGE 2 was shown to attenuate airway inflammation and the development of emphysema in cigarette smoking (CS)-exposed rats (12,13), supporting a role for COX-2 in the pathobiology of COPD.…”

Streptococcus pneumoniae-induced regulation of cyclooxygenase-2 in human lung tissue

“…They can lead to the activation of mitogenactivated protein kinases (MAPKs), which contribute to various important cell functions, including the regulation of inflammation. For example, p38 MAPK-dependent induction of COX-2 by bacteria and consecutive PG formation has been shown in cultured bronchial epithelium [11][12][13].…”

“…COX-1 is generally believed to be constitutively expressed, whereas COX-2 is the inducible isoform [10]. Induction is caused by a variety of stimuli including bacteria, viruses and cyto-/ chemokines [11][12][13][14]. They can lead to the activation of mitogenactivated protein kinases (MAPKs), which contribute to various important cell functions, including the regulation of inflammation.…”

Minimally modified LDL upregulates endothelin type B receptors in rat coronary artery via ERK1/2 MAPK and NF-κB pathways

“…NF-κB is a pivotal transcription factor down-stream of the MAPK and PKC pathways [19][20][21]. PKC participates in signal transduction events in response to specific hormonal, neuronal and growth factor stimuli [22].…”