HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chen, B.-C. Articles by Lin, C.-H. Search for Related Content PubMed PubMed Citation Articles by Chen, B.-C. Articles by Lin, C.-H.

Bradykinin B2 Receptor Mediates NF-B Activation and Cyclooxygenase-2 Expression via the Ras/Raf-1/ERK Pathway in Human Airway Epithelial Cells¹

Bing-Chang Chen^*, Chung-Chi Yu, Hui-Chieh Lei, Ming-Shyan Chang, Ming-Jen Hsu, Chuen-Lin Huang, Mei-Chieh Chen, Joen-Rong Sheu, Tseng-Fu Chen, Ta-Liang Chen^¶, Hiroyasu Inoue^|| and Chien-Huang Lin^*,

^* School of Respiratory Therapy, Graduate Institutes of Biomedical Technology, Graduate Institutes of Medical Sciences, Department of Microbiology and Immunology, College of Medicine, Taipei Medical University, Taipei, Taiwan; ^¶ Department of Anesthesiology, Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan; and ^|| Department of Pharmacology, National Cardiovascular Center Research Institute, Osaka, Japan

In this study, we investigated the signaling pathways involved in bradykinin (BK)-induced NF-B activation and cyclooxygenase-2 (COX-2) expression in human airway epithelial cells (A549). BK caused concentration- and time-dependent increase in COX-2 expression, which was attenuated by a selective B2 BK receptor antagonist (HOE140), a Ras inhibitor (manumycin A), a Raf-1 inhibitor (GW 5074), a MEK inhibitor (PD 098059), an NF-B inhibitor (pyrrolidine dithiocarbate), and an IB protease inhibitor (L-1-tosylamido-2-phenylethyl chloromethyl ketone). The B1 BK receptor antagonist (Lys-(Leu⁸)des-Arg⁹-BK) had no effect on COX-2 induction by BK. BK-induced increase in COX-2-luciferase activity was inhibited by cells transfected with the B site deletion of COX-2 construct. BK-induced Ras activation was inhibited by manumycin A. Raf-1 phosphorylation at Ser³³⁸ by BK was inhibited by manumycin A and GW 5074. BK-induced ERK activation was inhibited by HOE140, manumycin A, GW 5074, and PD 098059. Stimulation of cells with BK activated IB kinase (IKK), IB phosphorylation, IB degradation, p65 and p50 translocation from the cytosol to the nucleus, the formation of an NF-B-specific DNA-protein complex, and B-luciferase activity. BK-mediated increase in IKK activity and formation of the NF-B-specific DNA-protein complex were inhibited by HOE140, a Ras dominant-negative mutant (RasN17), manumycin A, GW 5074, and PD 098059. Our results demonstrated for the first time that BK, acting through B2 BK receptor, induces activation of the Ras/Raf-1/ERK pathway, which in turn initiates IKK and NF-B activation, and ultimately induces COX-2 expression in human airway epithelial cell line (A549).

This article has been cited by other articles:

				M.-J. Hsu, C. Y. Hsu, B.-C. Chen, M.-C. Chen, G. Ou, and C.-H. Lin Apoptosis Signal-Regulating Kinase 1 in Amyloid {beta} Peptide-Induced Cerebral Endothelial Cell Apoptosis J. Neurosci., May 23, 2007; 27(21): 5719 - 5729. [Abstract] [Full Text] [PDF]

				R. Williams, X. Zou, and G. W. Hoyle Tachykinin-1 receptor stimulates proinflammatory gene expression in lung epithelial cells through activation of NF-{kappa}B via a Gq-dependent pathway Am J Physiol Lung Cell Mol Physiol, February 1, 2007; 292(2): L430 - L437. [Abstract] [Full Text] [PDF]

				J. Arredondo, A. I. Chernyavsky, D. L. Jolkovsky, K. E. Pinkerton, and S. A. Grando Receptor-mediated tobacco toxicity: cooperation of the Ras/Raf-1/MEK1/ERK and JAK-2/STAT-3 pathways downstream of {alpha}7 nicotinic receptor in oral keratinocytes FASEB J, October 1, 2006; 20(12): 2093 - 2101. [Abstract] [Full Text] [PDF]

				R. Gedey, X.-L. Jin, O. Hinthong, and J. L. Shisler Poxviral Regulation of the Host NF-{kappa}B Response: the Vaccinia Virus M2L Protein Inhibits Induction of NF-{kappa}B Activation via an ERK2 Pathway in Virus-Infected Human Embryonic Kidney Cells. J. Virol., September 1, 2006; 80(17): 8676 - 8685. [Abstract] [Full Text] [PDF]

				C.-H. Lin, H.-W. Cheng, M.-J. Hsu, M.-C. Chen, C.-C. Lin, and B.-C. Chen c-Src Mediates Thrombin-Induced NF-{kappa}B Activation and IL-8/CXCL8 Expression in Lung Epithelial Cells. J. Immunol., September 1, 2006; 177(5): 3427 - 3438. [Abstract] [Full Text] [PDF]

				H.-W. Koon, D. Zhao, Y. Zhan, S. H. Rhee, M. P. Moyer, and C. Pothoulakis Substance P Stimulates Cyclooxygenase-2 and Prostaglandin E2 Expression through JAK-STAT Activation in Human Colonic Epithelial Cells. J. Immunol., April 15, 2006; 176(8): 5050 - 5059. [Abstract] [Full Text] [PDF]

				M. Shinkai, G. H. Foster, and B. K. Rubin Macrolide antibiotics modulate ERK phosphorylation and IL-8 and GM-CSF production by human bronchial epithelial cells Am J Physiol Lung Cell Mol Physiol, January 1, 2006; 290(1): L75 - L85. [Abstract] [Full Text] [PDF]

				A. Murakami, T. Shigemori, and H. Ohigashi Zingiberaceous and Citrus Constituents, 1'-Acetoxychavicol Acetate, Zerumbone, Auraptene, and Nobiletin, Suppress Lipopolysaccharide-Induced Cyclooxygenase-2 Expression in RAW264.7 Murine Macrophages through Different Modes of Action J. Nutr., December 1, 2005; 135(12): 2987S - 2992S. [Abstract] [Full Text] [PDF]

				P. S. Biswas, K. Banerjee, B. Kim, P. R. Kinchington, and B. T. Rouse Role of Inflammatory Cytokine-Induced Cycloxygenase 2 in the Ocular Immunopathologic Disease Herpetic Stromal Keratitis J. Virol., August 15, 2005; 79(16): 10589 - 10600. [Abstract] [Full Text] [PDF]