Figure 1.

Mechanism of neutrophil elastase (NE) induction of IL-8 in airway epithelial cells. Following its release from the azurophilic granules in response to a microbial insult, NE activates meprin-α or TNFα converting enzyme (TACE), which in turn cleave proTGFα to generate soluble TGFα as a ligand for the epidermal growth factor receptor (EGFR). EGFR co-localizes with TLR4 and a signal transduction cascade is initiated via MyD88 or Mal, IRAKs, TRAF6, transforming growth factor-beta-activated kinase 1 (TAK1) and the IκB kinases (IKKs), leading to a degradation of inhibitor of NFκB (IκB) proteins, activation of nuclear factor-κB (NFκB) and increased IL-8 gene transcription.