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Am J Physiol Lung Cell Mol Physiol 285: L925-L930, 2003. First published June 27, 2003; doi:10.1152/ajplung.00182.2002
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Neutrophil elastase stimulates human airway epithelial cells to produce PGE2 through activation of p44/42 MAPK and upregulation of cyclooxygenase-2

Diahn-Warng Perng,1,3,* Yu-Chung Wu,2,3,* Mei-Chuan Tsai,1 Ching-Ping Lin,2 Wen-Hu Hsu,2 Reury-Perng Perng,1,3 and Yu-Chin Lee1,3

1Department of Chest Medicine, 2Division of Chest Surgery, Taipei Veterans General Hospital; and 3School of Medicine, National Yang-Ming University, Taipei 11217, Taiwan

Submitted 7 June 2002 ; accepted in final form 20 June 2003

The responses of airway epithelium following exposure to neutrophil elastase (NE) were investigated. Human bronchial epithelial cells were explanted on insert surfaces of a modified air-liquid interface culture system to which NE was added to stimulate epithelial cells. PGE2 release significantly increased within 10 min of incubation with NE and peaked 3 h after NE (20 µg/ml) stimulation. This action required proteolytic activity as {alpha}1-antitrypsin blocked NE-induced PGE2 release. The production of PGE2 was also inhibited by indomethacin; a selective cyclooxygenase (COX)-2 inhibitor, celecoxib; and dexamethasone. Moreover, the mRNA expression for COX-2 relative to that for a housekeeping gene was approximately eightfold that of the unstimulated cells. Dexamethasone inhibited COX-2 gene transcription. We further observed that NE-induced PGE2 release involved activation of p44/42, but not p38, MAP kinases. Such p44/42 MAP kinases were rapidly phosphorylated, with the concentration of phosphorylated p44/42 MAP kinases peaking at 10 min after stimulation and declining in culture at 90 min. The specific p44/42 MAP kinase inhibitor UO126 completely blocked p44/42 phosphorylation and, subsequently, PGE2 production. The airway epithelium may play important bronchoprotective and immunomodulatory roles in chronic neutrophilic inflammation.

human bronchial epithelial cell; prostaglandin E2; chronic neutrophilic inflammation


Address for reprint requests and other correspondence: D.-W. Perng and Y.-C. Lee, Dept. of Chest Medicine, Taipei Veterans General Hospital, 201, Section 2, Shih-Pai Rd., Taipei 11217, Taiwan (E-mail: dwperng{at}vghtpe.gov.tw).




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