Fig. 6.

IL-17A and/or transforming growth factor-β1 (TGF-β1) signaling induce secretion of an array of inflammatory factors from airway epithelial, smooth muscle, and fibroblast cells. Moreover, several of these factors promote enhanced airway remodeling and phenotypic switching between structural airway cells. Dynamic cellular cross talk between cells within the airway architecture elevates expression of remodeling proteins beyond that seen within isolated cells following IL-17A and/or TGF-β1 treatment. In individuals with severe asthma, these interactions are suggested to be responsible for increased cellular migration, reduced epithelial integrity, thickened airway smooth muscle (ASM) layers, and a marked degree of airway obstruction and reduced airflow. bFGF, basic fibroblast growth factor; CCL19, C-C motif chemokine 19; CCR7, C-C chemokine receptor 7; COL, collagen; COX-2, cyclooxygenase-2; CXCL1, C-X-C motif chemokine ligand 1; EMT, epithelial-mesenchymal transition; G-CSF, granulocyte colony-stimulating factor; GM-CSF, granulocyte-macrophage colony-stimulating factor; MMPs, matrix metalloproteinases; MUC, mucin; ROS, reactive oxygen species; α-SMA, α-smooth muscle actin; WNT5A, protein Wnt-5a.