Autocrine Ligands for the Epidermal Growth Factor Receptor Mediate Interleukin-8 Release from Bronchial Epithelial Cells in Response to Cigarette Smoke

Airway neutrophilia is a prominent feature of chronic obstructive pulmonary disease. As cigarette smoke (CS) and epidermal growth factor (EGF) both cause release of interleukin-8 (IL-8) from epithelial cells in vitro, we investigated whether autocrine ligands for the EGF receptor (EGFR) are involved in this proinflammatory response to CS. NCI-H292 or primary bronchial epithelial cells were cultured with or without cigarette smoke extract (CSE) or EGF for 6–48 h. We then tested culture supernatants for lactate dehydrogenase activity to assess cell viability, and for IL-8 and EGFR ligands by ELISA; quantitative RT-PCR was used to measure IL-8 and EGFR ligand mRNA. EGF and low concentrations of CSE both promoted cell survival and caused enhanced transcription and release of IL-8. Similarly, levels of mRNA encoding transforming growth factor α (TGF- α ), heparin-binding EGF-like growth factor, and amphiregulin (AR) were increased, as was shedding of TGF- α and AR protein into the culture medium. With the exce...