TAILIEUCHUNG - Báo cáo khoa học: Human airway trypsin-like protease induces amphiregulin release through a mechanism involving protease-activated receptor-2-mediated ERK activation and TNF a-converting enzyme activity in airway epithelial cells

Human airway trypsin-like protease (HAT), a serine protease found in the sputum of patients with chronic airway diseases, is an agonist of protease-activated receptor-2 (PAR-2). Previous results have shown that HAT enhances the release of amphiregulin (AR); further, it causes MUC5AC gene expression through the AR-epidermal growth factor receptor pathway in the airway epithelial cell line NCI-H292. | ềFEBS Journal Human airway trypsin-like protease induces amphiregulin release through a mechanism involving protease-activated receptor-2-mediated ERK activation and TNF a-converting enzyme activity in airway epithelial cells Manabu Chokki Hiroshi Eguchi Ichiro Hamamura Hiroaki Mitsuhashi and Takashi Kamimura PharmaceuticalDiscovery Research Laboratories Institute for Bio-MedicalResearch Teijin Pharma Limited Tokyo Japan Keywords amphiregulin extracellular signal-regulated kinase human airway trypsin-like protease protease-activated receptor-2 tumour necrosis factor a-converting enzyme Correspondence M. Chokki PharmaceuticalDiscovery Research Laboratories Institute for BioMedical Research Teijin Pharma Limited Tokyo Japan Tel 81 42 586 8134 Fax 81 42 587 5515 E-mail Received 15 September 2005 revised 20 October 2005 accepted 26 October 2005 doi Human airway trypsin-like protease HAT a serine protease found in the sputum of patients with chronic airway diseases is an agonist of protease-activated receptor-2 PAR-2 . Previous results have shown that HAT enhances the release of amphiregulin AR further it causes MUC5AC gene expression through the AR-epidermal growth factor receptor pathway in the airway epithelial cell line NCI-H292. In this study the mechanisms by which HAT-induced AR release can occur were investigated. HAT-induced AR gene expression was mediated by extracellular signal-regulated kinase ERK pathway as pretreatment of cells with ERK pathway inhibitor eliminated the effect of HAT on AR mRNA. Both HAT and PAR-2 agonist peptide PAR-2 AP induced ERK phosphorylation further desensitization of PAR-2 with a brief exposure of cells to PAR-2 AP resulted in inhibition of HAT-induced ERK phosphorylation suggesting that HAT activates ERK through PAR-2. Moreover PAR-2 AP induced AR gene expression subsequent to protein production in the cellular fraction through the ERK pathway indicating that .

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