PT  - JOURNAL ARTICLE
AU  - Marc Dubourdeau
AU  - Gerald Chene
AU  - Vincent Baillif
AU  - Charlotte Guigne
AU  - Estelle Wanecq
AU  - Emeline Van Goethem
TI  - Specialized-proresolving mediators and trancriptomic signatures in bleomycin-induced lung fibrosis
AID  - 10.1183/13993003.congress-2016.PA4041
DP  - 2016 Sep 01
TA  - European Respiratory Journal
PG  - PA4041
VI  - 48
IP  - suppl 60
4099  - http://erj.ersjournals.com/content/48/suppl_60/PA4041.short
4100  - http://erj.ersjournals.com/content/48/suppl_60/PA4041.full
SO  - Eur Respir J2016 Sep 01; 48
AB  - Idiopathic pulmonary fibrosis (IPF) is a disease with unknown origin. IPF is characterized by the apparition of collagen fibers into the lung parenchyma, leading to an excessive and irreversible healing of the tissue, associated with a loss of its function. Following the description of specialized mediators of inflammation resolution (SPMs) and their potential involvement in the control of fibrosis, we decided to study resolution pathways in an animal model of pulmonary fibrosis to help deciphering mechanisms involved in IPF.Mice were inoculated with bleomycin and mediators issued from fatty acids were analyzed using mass spectrometry. RNA expression was evaluated thanks to a dynamic array.We have shown an increase of PGE2, TXB2, PGD2 and 15-HETE, mediators depending on the arachidonic acid pathways. For EPA metabolites, we demonstrated an increase of PGE3, 15-HEPE and 18-HEPE the precursor of resolvins of type E. Finally, we observed DHA metabolites with an increase of 13-HDoHE and 17-HDoHE but also of RvD2. For trancriptomic experiments, we notably noticed an overexpression of inflammatory genes (such as COX1, IL6, Ccl1, MCP-1) and genes involved in the remodeling of the extracellular matrix (Col1, Fn1, Mmp2, Timp1).The results suggest that fibrosis context is associated with an inflammatory status that did not seem to be counterbalanced by production of SPMs. Indeed, even if RvD2 is increased and the enzymes COX and 15-LOX activated (as seen with production of PGE2 and 15-HETE), none of the other SPMs were detected. These results might thus draw the first evidence of a defect during fibrosis to produce a complete network of SPMs.