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

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.