Variable prostaglandin E2 resistance in fibroblasts from patients with usual interstitial pneumonia. Academic Article uri icon

Overview

MeSH

  • Adult
  • Aged
  • Aged, 80 and over
  • Cell Division
  • Cell Line
  • Collagen Type I
  • Cyclic AMP
  • Drug Resistance
  • Female
  • Humans
  • Lung
  • Male
  • Middle Aged
  • Pulmonary Fibrosis

MeSH Major

  • Dinoprostone
  • Fibroblasts
  • Lung Diseases, Interstitial

abstract

  • Prostaglandin (PG) E2, a cyclooxygenase-derived lipid mediator, is a potent down-regulator of fibroblast activation in normal lung fibroblasts. Although fibroblasts from patients with idiopathic pulmonary fibrosis are known to exhibit a defect in PGE2 synthesis, there is little information about their responsiveness to this lipid mediator. To compare responses to PGE2 in normal, usual interstitial pneumonia (UIP), and other diffuse parenchymal lung disease (DPLD) fibroblasts. Fibroblasts were grown in vitro from well characterized control (n = 7), UIP (n = 17), or other DPLD (n = 13) lung tissue. The effects of PGE2 on fibroblast proliferation and collagen expression were determined. Only 3 of 12 UIP fibroblast lines exhibited PGE2-mediated inhibition of both collagen synthesis and cell proliferation, as opposed to 6 of 6 nonfibrotic control cell lines. The degree of PGE2 resistance in DPLD fibroblasts was quite variable, with UIP cells exhibiting the greatest degree of resistance to PGE2, whereas other DPLD fibroblasts manifested a degree of resistance intermediate to control and UIP. The resistance to suppression of collagen expression correlated with worse lung function. Molecular mechanisms for resistance included altered E prostanoid receptor profiles and diminished expression of the downstream kinase, protein kinase A. The recognition that UIP fibroblasts manifest variable refractoriness to PGE2 suppression sheds new light on the activation phenotype of these cells and on the pathogenesis of fibrotic lung disease.

publication date

  • January 1, 2008

has subject area

  • Adult
  • Aged
  • Aged, 80 and over
  • Cell Division
  • Cell Line
  • Collagen Type I
  • Cyclic AMP
  • Dinoprostone
  • Drug Resistance
  • Female
  • Fibroblasts
  • Humans
  • Lung
  • Lung Diseases, Interstitial
  • Male
  • Middle Aged
  • Pulmonary Fibrosis

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC2176116

Digital Object Identifier (DOI)

  • 10.1164/rccm.200706-963OC

PubMed ID

  • 17916807

Additional Document Info

start page

  • 66

end page

  • 74

volume

  • 177

number

  • 1