Effects of thoracic irradiation on pulmonary endothelial compared to alveolar type-II cells in fibrosis-prone C57BL/6NTac mice

In Vivo. 2013 May-Jun;27(3):291-7.

Abstract

Background/aim: Thoracic irradiation results in an acute inflammatory response, latent period, and late fibrosis. Little is known about the mechanisms involved in triggering late radiation fibrosis.

Materials and methods: Thoracic irradiated fibrosis prone C57BL/6NTac mice were followed for detectable mRNA transcripts in isolated lung cells and micro-RNA in whole-tissues, and the effect of administration of water-soluble oxetanyl sulfoxide MMS350 was studied. Marrow stromal cell motility in medium from fibrotic-phase explanted pulmonary endothelial and alveolar type-II cells was measured.

Results: RNA and micro-RNA expression in lung correlated with fibrosis. MMS350 reduced pro-fibrotic gene expression in both endothelial and alveolar type-II cells in irradiated mice. Conditioned medium from irradiated cells did not alter cell motility in vitro.

Conclusion: These studies should facilitate identification of potential new drug targets for ameliorating irradiation-induced pulmonary fibrosis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alveolar Epithelial Cells / drug effects
  • Alveolar Epithelial Cells / metabolism
  • Alveolar Epithelial Cells / radiation effects*
  • Animals
  • Cytokines / biosynthesis
  • Disease Models, Animal
  • Ethers, Cyclic / metabolism*
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / radiation effects
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / genetics
  • Pulmonary Alveoli / drug effects
  • Pulmonary Alveoli / metabolism
  • Pulmonary Alveoli / radiation effects*
  • Pulmonary Fibrosis / etiology*
  • Pulmonary Fibrosis / genetics
  • Pulmonary Fibrosis / pathology
  • Radiation Pneumonitis* / genetics
  • Radiation Pneumonitis* / pathology
  • Radiotherapy / adverse effects*
  • Signal Transduction / drug effects
  • Signal Transduction / radiation effects
  • Stromal Cells / drug effects
  • Stromal Cells / metabolism
  • Stromal Cells / radiation effects
  • Sulfoxides / metabolism*
  • Transcription, Genetic / drug effects
  • Transcription, Genetic / radiation effects

Substances

  • Cytokines
  • Ethers, Cyclic
  • MMS350
  • MicroRNAs
  • Sulfoxides