Figure 2.

Proinflammatory and profibrotic mediators in the initiation and maintenance of fibrosis. Irritants like silica, asbestos, and bleomycin (uric acid) can injure lung epithelial cells and can be detected by the Nalp3 inflammasome in macrophages. These irritants stimulate the production of ROS, chemokines, and cytokines. These inflammatory mediators enhance the recruitment and activation of leukocytes at the site of tissue injury. For example, IL-1β induces the activation of ROS-expressing neutrophils, which can further damage epithelial cells. IL-1β also promotes production of TGF-β1, an important profibrotic cytokine that triggers fibroblast proliferation and activation. TGF-β also targets epithelial cells, inducing EMT and the formation of ECM-producing myofibroblasts. TGF-β1 further exacerbates the inflammatory response by stimulating the differentiation of Th17 cells. Interactive PPT slides for this figure are available online.