TY - JOUR T1 - 17(R)-resolvinD1 improves MMP-9/TIMP-1 imbalance leading to amelioration of pulmonary fibrosis in mice JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.congress-2016.PA3094 VL - 48 IS - suppl 60 SP - PA3094 AU - Masakiyo Yatomi AU - Takeshi Hisada AU - Yoshimasa Hachisu AU - Yasuyuki Saito AU - Hiroaki Tsurumaki AU - Yosuke Kamide AU - Haruka Aoki-Saito AU - Yasuhiko Koga AU - Akihiro Ono AU - Kunio Dobashi AU - Tamotsu Ishizuka AU - Masanobu Yamada AU - Fumikazu Okajima Y1 - 2016/09/01 UR - http://erj.ersjournals.com/content/48/suppl_60/PA3094.abstract N2 - Idiopathic pulmonary fibrosis (IPF) is a chronic inflammatory disease with progressive destruction and dysfunction. Currently, none of therapies has great impact on long-term survival of IPF. 17(R)-ResolvinD1 (RvD1) is well known as a lipid mediator which has potent anti-inflammatory pro-resolving activity. Previous reports have shown RvD1 is efficacious on some inflammatory diseases through promotion of resolution. However, the effect of RvD1 on lung fibrosis which has been already formed remains unclear. Enhanced collagen deposition underlying IPF partly depends on matrix metalloproteinase 9 (MMP-9)/tissue inhibitor of metalloproteinase 1 (TIMP-1) imblance. Based on this knowledge, we aimed to develop potent bioactions of RvD1. We used 8 week old female C57BL/6J mice divided into 4 groups: Saline (Sal)/vehicle (veh), bleomycin (BLM)/veh, Sal/RvD1, BLM/RvD1. We administered BLM subcutaneously via micro-osmotic pump and RvD1 intraperitoneally for 5 days consecutively from day 21, during fibrotic stage. At day 28, we measured cell differentiation in bronchoaveloar fluid (BALF), histology, hydroxyproline contents, CT image and mRNA of lung tissue in each group. In BLM/RvD1 group, neutrophils and macrophages in BALF were significantly decreased. Also, histology exhibited less collagen deposition and hydroxyproline content was significantly reduced. Furthermore, the decrease in lung density, as visualized by CT image, was observed. Interestingly, RvD1 brought to normal levels of MMP-9 mRNA with declining TIMP-1 mRNA even though BLM made MMP-9 mRNA decrease markedly. Our results suggest that RvD1 provides pulmonary restoration via improving MMP-9/TIMP-1 imbalance on lung fibrosis. ER -