Source: Annual Congress 2003 - Molecular biology of chronic lung disease and lung cancer
Disease area: Interstitial lung diseases

Abstract

Radiotherapy is important in the treatment of lung cancer. A major problem is irradiation induced damage of the lung. Various pulmonary cells are involved in the pathogenesis of this disorder. They produce growth factors, such as TGFbeta, and are also stimulated by these cytokines.
We investigated the effect of irradiated lung fibroblasts, macrophages and alveolar epithelial cells on proliferation (BrdU), cell cycle (FACS) and collagen synthesis (3H-Prolin) of untreated fibroblasts in vitro.
Conditioned media of irradiated fibroblasts and macrophages inhibit the proliferation of untreated cells one week after irradiation in a dose dependent manner. By pulse labelling with BrdU we demonstrated a cell cycle arrest of non-irradiated fibroblasts suggesting terminal differentiation into post-mitotic cells. In addition, supernatants of both cell types induced a two fold increase of collagen synthesis when incubated with non-irradiated fibroblasts (p=0.001). Similar observations were made after addition of recombinant TGFbeta. Conditioned media from irradiated epithelial cells had no comparable effects.
We suggest that the pathogenesis of radiation induced lung disease is more likely influenced by the cross talk between alveolar macrophages and stromal cells, and not by alveolar epithelial cells. TGFbeta might be involved, and inhibition of this profibrotic cytokine should be evaluated as a therapeutic strategy in radiation fibrosis.
Supported by Stiftung Deutsche Krebshilfe. M.K. is a Parker B. Francis Fellow

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Citations should be made in the following way:
K. Meyer, S. Seger, J. Willner, M. Schmidt, M. Kolb (Wuerzburg, Germany; Hamilton, Canada). Macrophages and fibroblasts induce pro-fibrotic effects following irradiation. Eur Respir J 2003; 22: Suppl. 45, 1493

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