Resistance of fibrogenic responses to glucocorticoid and 2-methoxyestradiol in bleomycin-induced lung fibrosis in mice

Shenna Y Langenbach, Ben J Wheaton, Darren J Fernandes, Catherine Jones, Tara E Sutherland, Bronwyn C Wraith, Trudi Harris, Michael J Schuliga, Catriona McLean, Alastair G Stewart

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

Abstract

Bleomycin-induced lung fibrosis in mice reproduces some key features of pulmonary fibrosis in humans including alveolar inflammation, myofibroblast proliferation, and collagen deposition. Glucocorticoids have been used as first-line therapy for the treatment of lung fibrosis, although their clinical efficacy is equivocal. We examined the effect of the glucocorticoid, methylprednisolone (MP), and the estrogen metabolite, 2-methoxyestradiol (2MEO) on bleomycin-induced bronchoalveolar inflammation, fibrosis, and changes in lung function. The characterization of the time-course of the bleomycin-induced fibrosis indicated that lung dry mass and hydroxyproline content showed less variance than histopathological assessment of fibrosis. The bleomycin-induced increases in bronchoalveolar lavage (BAL) fluid cell number and protein levels were not significantly influenced by treatment with either MP (1 mg.(kg body mass)(-1).day(-1), i.p.) or 2MEO (50 mg.(kg body mass)(-1).day(-1), i.p.). Lung fibrosis, measured histopathologically or by hydroxyproline content, was not significantly influenced by either MP or 2MEO treatment, whereas the latter agent did reduce the increment in lung dry mass. The enlargement of alveolar airspaces and the decline in lung compliance were exacerbated by MP treatment. These data suggest that bleomycin-induced pulmonary fibrosis is resistant to inhibition by concurrent treatment with either glucocorticoids or 2MEO.
Original languageEnglish
Pages (from-to)727-738
JournalCanadian Journal of Physiology and Pharmacology
Volume85
Issue number7
Early online date1 Jul 2007
DOIs
Publication statusPublished - 22 Aug 2007

Keywords

  • Airway Resistance
  • Animals
  • Bleomycin
  • Body Weight
  • Bronchoalveolar Lavage Fluid
  • Cell Adhesion Molecules
  • Cytokines
  • Drug Resistance
  • Estradiol
  • Gene Expression
  • Glucocorticoids
  • Hydroxyproline
  • Lung
  • Lung Compliance
  • Matrix Metalloproteinases
  • Methylprednisolone
  • Mice
  • Inbred C57BL
  • Organ Size
  • Pulmonary Alveoli
  • Pulmonary Emphysema
  • Pulmonary Fibrosis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tissue Inhibitor of Metalloproteinases
  • Tubulin Modulators

Fingerprint

Dive into the research topics of 'Resistance of fibrogenic responses to glucocorticoid and 2-methoxyestradiol in bleomycin-induced lung fibrosis in mice'. Together they form a unique fingerprint.

Cite this