6533b858fe1ef96bd12b5b9d
RESEARCH PRODUCT
Lung myofibroblasts are characterized by down-regulated cyclooxygenase-2 and its main metabolite, prostaglandin E2.
Jordi Roca-ferrerLaura PujolsJavier PeredaJavier PeredaDolores RoyoMaria Molina-molinaAntoni XaubetMarta GabasaCésar Picadosubject
PathologyPulmonologyMetaboliteImmunofluorescencelcsh:MedicineBiochemistrychemistry.chemical_compoundIdiopathic pulmonary fibrosisMolecular Cell BiologyPulmonary fibrosisProstaglandin E2Myofibroblastslcsh:ScienceLungCells CulturedFisiologia cel·lularMultidisciplinarybiologyFibrosi pulmonarrespiratory systemExtracellular Matrixmedicine.anatomical_structureCytokinesMedicinelipids (amino acids peptides and proteins)Immunohistochemical AnalysisMyofibroblastResearch ArticleSignal Transductionmedicine.drugmedicine.medical_specialtyEpithelial-Mesenchymal TransitionImmunologyInterstitial Lung DiseasesDinoprostonePulmonary fibrosisTransforming Growth Factor beta1ImmunofluorescènciaGrowth FactorsCell Line TumormedicineHumansEpithelial–mesenchymal transitionFibroblastBiologyCell Proliferationlcsh:RProteinsEpithelial Cellsmedicine.diseaseActinsIdiopathic Pulmonary Fibrosisrespiratory tract diseasesGene Expression RegulationchemistryCyclooxygenase 2Immune SystemCase-Control StudiesImmunologic Techniquesbiology.proteinCancer researchClinical Immunologylcsh:QCyclooxygenaseBiomarkersdescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2013-06-03 | PLoS ONE |