dc.contributor.author |
Gabasa Ferràndez, Marta |
dc.contributor.author |
Royo, Dolores |
dc.contributor.author |
Molina Molina, María |
dc.contributor.author |
Roca i Ferrer, Jordi |
dc.contributor.author |
Pujols Tarrés, Laura |
dc.contributor.author |
Picado Vallés, César |
dc.contributor.author |
Xaubet Mir, Antonio |
dc.contributor.author |
Pereda, Javier |
dc.date |
2018-11-27T09:20:32Z |
dc.date |
2018-11-27T09:20:32Z |
dc.date |
2013-06-03 |
dc.date |
2018-07-24T12:48:07Z |
dc.identifier.uri |
http://hdl.handle.net/2445/126461 |
dc.format |
13 p. |
dc.format |
application/pdf |
dc.language.iso |
eng |
dc.publisher |
Public Library of Science (PLoS) |
dc.relation |
Reproducció del document publicat a: https://doi.org/10.1371/journal.pone.0065445 |
dc.relation |
PLoS One, 2013, vol. 8, num. 6, p. e65445 |
dc.relation |
https://doi.org/10.1371/journal.pone.0065445 |
dc.rights |
cc by (c) Gabasa et al., 2013 |
dc.rights |
info:eu-repo/semantics/openAccess |
dc.rights |
http://creativecommons.org/licenses/by/3.0/es/ |
dc.subject |
Fibrosi pulmonar |
dc.subject |
Immunofluorescència |
dc.subject |
Pulmonary fibrosis |
dc.subject |
Immunofluorescence |
dc.title |
Lung Myofibroblasts Are Characterized by DownRegulated
Cyclooxygenase-2 and Its Main Metabolite,
Prostaglandin E2 |
dc.type |
info:eu-repo/semantics/article |
dc.type |
info:eu-repo/semantics/publishedVersion |
dc.description.abstract |
Background: Prostaglandin E2 (PGE(2)), the main metabolite of cyclooxygenase (COX), is a well-known anti-fibrotic agent. Moreover, myofibroblasts expressing alpha-smooth muscle actin (alpha-SMA), fibroblast expansion and epithelial-mesenchymal transition (EMT) are critical to the pathogenesis of idiopathic pulmonary fibrosis (IPF). Our aim was to investigate the expression of COX-2 and PGE(2) in human lung myofibroblasts and establish whether fibroblast-myofibroblast transition (FMT) and EMT are associated with COX-2 and PGE(2) down-regulation. Methods: Fibroblasts obtained from IPF patients (n = 6) and patients undergoing spontaneous pneumothorax (control, n = 6) and alveolar epithelial cell line A549 were incubated with TGF-beta 1 and FMT and EMT markers were evaluated. COX-2 and alpha-SMA expression, PGE(2) secretion and cell proliferation were measured after IL-1 beta and PGE(2) incubation. Results: Myofibroblasts from both control and IPF fibroblast cultures stimulated with IL-1 beta showed no COX-2 expression. IPF fibroblasts showed increased myofibroblast population and reduced COX-2 expression in response to IL-1 beta. TGF-beta 1 increased the number of myofibroblasts in a time-dependent manner. In contrast, TGF-beta 1 induced slight COX-2 expression at 4 h (without increase in myofibroblasts) and 24 h, but not at 72 h. Both IPF and control cultures incubated with TGF-beta 1 for 72 h showed diminished COX-2 induction, PGE(2) secretion and alpha-SMA expression after IL-1 beta addition. The latter decreased proliferation in fibroblasts but not in myofibroblasts. A549 cells incubated with TGF-beta 1 for 72 h showed down-regulated COX-2 expression and low basal PGE(2) secretion in response to IL-1 beta. Immuno-histochemical analysis of IPF lung tissue showed no COX-2 immuno-reactivity in myofibroblast foci. Conclusions: Myofibroblasts are associated with COX-2 down-regulation and reduced PGE(2) production, which could be crucial in IPF development and progression. |