Figure 2.

Schematic figure describing the development of radiation-induced chronic lung fibrosis. Radiation causes damage to pneumocytes and induces secondary reactive oxygen species that contribute to a pro-inflammatory environment. Acutely injured lung triggers healing mechanisms that activate (myo)fibroblasts. Excessive accumulation of collagen, which normally inhibits further fibroblast growth, selects for pro-fibrotic, viable lung fibroblasts. Fibroblast activation and selection combined with the inflammatory cytokine cascade, epithelial to mesenchymal transition (EMT), and loss of parenchymal cells leads to ongoing lung fibrosis. The bidirectional arrow indicates that cell death creates inflammatory cytokine production which further increases cell death.