The EGFR-ADAM17 Axis in Chronic Obstructive Pulmonary Disease and Cystic Fibrosis Lung Pathology

Figure 6

Classic and trans IL-6R signaling. In “classic” signaling membrane-bound IL-6R stimulated by secreted IL-6 associates with a homodimer of signal transducing glycoprotein (gp130) to activate downstream signaling molecules, including the ubiquitous transcription factor STAT-3. In trans-signaling, the soluble form of IL-6R (sIL-6R,) generated either by ADAM17 or by alternative mRNA splicing, binds to IL-6 and this IL-6/IL-6R complex activates gp130 on the airway epithelial cells (autocrine IL-6R trans-signaling) or underlying fibroblasts, myoblasts, or smooth muscle cells that do not express IL-6R (paracrine IL-6R trans-signaling), but do express gp130 to evoke activation of STAT-3 signaling.