Mucus Hypersecretion in Chronic Obstructive Pulmonary Disease and Its Treatment

Figure 2

Pathways leading to mucus hypersecretion TNF-α interacts with cell surface receptors and stimulates the EGFR gene in airway epithelial cells. IκB kinase (IKK) activation is induced by receptor stimulation. The IκB subunit of intracellular NF-κB is then phosphorylated (P) by IKK at its regulatory site, allowing for transactivation and degradation. This, in turn, releases NF-κB dimers and causes free NF-κB to move into the nucleus, where it activates the expression of target genes MUC5AC. IL-13 activates Janus kinase 1 (Jak1) to phosphorylate (P) STAT6 after binding to IL-4Rα receptors. STAT6 activation increases the expression of SPDEF, which upregulates mucous metaplasia genes and reduces forkhead box A2 (Foxa2), which negatively regulates MUC5AC.