Tryptase and agonists of PAR-2 induce the proliferation of human airway smooth muscle cells

Citation
P. Berger et al., Tryptase and agonists of PAR-2 induce the proliferation of human airway smooth muscle cells, J APP PHYSL, 91(3), 2001, pp. 1372-1379
Citations number
46
Categorie Soggetti
Physiology
Journal title
JOURNAL OF APPLIED PHYSIOLOGY
ISSN journal
87507587 → ACNP
Volume
91
Issue
3
Year of publication
2001
Pages
1372 - 1379
Database
ISI
SICI code
8750-7587(200109)91:3<1372:TAAOPI>2.0.ZU;2-D
Abstract
Airway remodeling with smooth muscle cell (SMC) hyperplasia is a feature of chronic asthma. We investigated the potential for tryptase, the major secr etory product of human mast cells, to act as a growth factor for human airw ay SMCs. Because this serine protease can activate proteinase-activated rec eptor-2 (PAR-2), we also examined the actions of SLIGKV, a peptide agonist of PAR-2. Incubation with lung tryptase provoked a twofold increase in [H-3 ] thymidine incorporation; a similar increase in cell numbers was found whe n we used the MTS assay. The effect was catalytic site dependent, being abo lished by the protease inhibitors leupeptin and benzamidine and by heat ina ctivation of the enzyme. Tryptase-induced DNA synthesis was inhibited by pr eincubation of the cells with pertussis toxin, calphostin C, or genistein. Transduction mechanisms are thus likely to involve a pertussis toxin-sensit ive G protein, protein kinase C, and tyrosine kinase. SLIGKV elicited a res ponse on SMCs similar to that of tryptase. Tryptase could provide an import ant stimulus for SMC proliferation in asthmatic airways, by acting on PAR-2 .