RT Journal Article
SR Electronic
T1 The YKL-40-increased bronchial smooth muscle cell proliferation and migration is PAR-2 dependant
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP p747
VO 38
IS Suppl 55
A1 Imane Bara
A1 Annaig Ozier
A1 Pierre-Olivier Girodet
A1 Jennifer Cattiaux
A1 Roland Kolbeck
A1 Anthony Coyle
A1 Jose-Manuel Tunon de Lara
A1 Roger Marthan
A1 Patrick Berger
YR 2011
UL http://erj.ersjournals.com/content/38/Suppl_55/p747.abstract
AB Background: In asthma, the decrease in lung function has been associated with an increased mass of bronchial smooth muscle (BSM). However, the mechanism of such remodelling remains largely unknown. We focused our attention on chitinase 3-like 1 protein YKL-40, since we previously reported that it altered the physiological properties of BSM cells and is highly secreted by inflammatory cells and epithelial cells from severe asthmatics.Objectives: The objectives were to study the mechanisms underlying the effects of YKL-40 on human BSM cell proliferation and migration.Methods: YKL-40 was kindly provided by MedImmune. Human BSM cells were cultured from controls (n=7) and asthmatics (n=6). BSM cell proliferation was assessed using BrdU incorporation. Cell migration was evaluated using inserts. Transduction mechanisms were assessed using several inhibitors of signal transduction pathways (Pertussis toxin, Calphostin, PD98059, SB203580, LY294002). The involvement of protease activated receptor-2 (PAR-2) was evaluated using an anti-PAR-2 blocking antibody.Results: YKL-40 significantly increased by more than two fold BSM cell BrdU incorporation within 24h incubation and cell number within 48h. Following 24h incubation, YKL-40 significantly increased BSM cell migration. These effects were inhibited by blocking PAR-2 antibody in both asthmatic and control BSM cells. Transduction mechanisms of cell proliferation and migration involved Gi protein, protein kinase C, MAPK/ERK pathways.Conclusion: These results confirm that the chitinase YKL-40-induced BSM cell hyperplasia was PAR-2-dependant.