TY - JOUR T1 - Human airway trypsin-like protease: Friend or foe in idiopathic pulmonary fibrosis? JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.congress-2016.PA4037 VL - 48 IS - suppl 60 SP - PA4037 AU - Awen Menou AU - Sophie Moog AU - Bruno Crestani AU - Keren Borenstajn Y1 - 2016/09/01 UR - http://erj.ersjournals.com/content/48/suppl_60/PA4037.abstract N2 - Introduction: Human Airway Trypsin-like protease (HAT) belongs to the membrane-anchored serine proteases family. While its physiological functions remain unknown, HAT is involved in pulmonary remodeling processes like asthma. In airways HAT stimulates fibroblast proliferation thought Protease-Activated Receptor-2, a pro-fibrotic receptor in IPF, but its role in IPF has never been investigated so far.Methods: In controls or patients with IPF, HAT expression was analysed in lung biopsies by immunohistochemistry and by Western-blot (WB) in lung homogenates, Broncho-Alveolar Lavages (BAL) and primary pulmonary fibroblasts. In homogenates and BAL, HAT activity was measured with a specific chromogenic substrate. In vitro, the effects of HAT on fibrotic markers expression, migration and proliferation were assessed in human primary pulmonary fibroblasts using WB, WST-1 and Boyden chamber assays. HAT expression and activity were measured in a mouse model of bleomycin-induced lung fibrosis.Results: HAT is prominent in IPF lungs in epithelial cells and (myo)fibroblasts. HAT expression and activity are enhanced in the lung and BAL from IPF patients. Results were similar in fibrotic mice. In fibroblasts, HAT induces decreases fibronectine and collagen expression, does not increase pulmonary fibroblasts proliferation and strongly decreases migration.Conclusions: In IPF, contrary to its deleterious role in chronic inflammatory disease, HAT induces anti-fibrotic responses in vitro. Its deregulated expression in IPF could constitute an insufficient mechanism of protection. These results should be confirmed in HAT-deficient mice. Our results suggest that an induction of HAT in IPF could be beneficial. ER -