title: Diesel exhaust increases EGFR and phosphorylated C-terminal Tyr 1173 in the bronchial epithelium.
abstract: BACKGROUND
  Epidemiological studies have demonstrated adverse health effects of environmental pollution. Diesel exhaust (DE) is a major contributor to particulate matter pollution. DE exposure has been shown to induce a pronounced inflammatory response in the airways, together with an enhanced epithelial expression of cytokines such as IL-8, Gro-alpha, IL-13 and activation of redox sensitive transcription factors (NFkappaB, AP-1), and MAP kinases (p38, JNK). The aim of the present investigation was to elucidate the involvement of the epidermal growth factor receptor (EGFR) signalling pathway in the epithelial response to DE in-vivo.
  
  
  RESULTS
  Immunohistochemical staining was used to quantify the expression of the EGFR, phosphorylated Tyrosine residues, MEK and ERK in the bronchial epithelium of archived biopsies from 15 healthy subjects following exposure to DE (PM10, 300 mug/m3) and air. DE induced a significant increases in the expression of EGFR (p = 0.004) and phosphorylated C-terminal Tyr 1173 (p = 0.02). Other investigated EGFR tyrosine residues, Src related tyrosine (Tyr 416), MEK and ERK pathway were not changed significantly by DE.
  
  
  CONCLUSIONS
  Exposure to DE (PM10, 300 mug/m3) caused enhanced EGFR expression and phosphorylation of the tyrosine residue (Tyr 1173) which is in accordance with the previously demonstrated activation of the JNK, AP-1, p38 MAPK and NFkB pathways and associated downstream signalling and cytokine production. No effects were seen on the MEK and ERK pathway suggesting that at the investigated time point (6 hours post exposure) there was no proliferative/differentiation signalling in the bronchial epithelium. The present findings suggest a key role for EGFR in the bronchial response to diesel exhaust.
authors.affiliation: Department of Respiratory Medicine and Allergy, University Hospital, Umeå, Sweden. thomas.sandstrom@lung.umu.se.
authors.forename: Jamshid
authors.initials: J
authors.lastname: Pourazar
authors.forename: Anders
authors.initials: A
authors.lastname: Blomberg
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Kelly
authors.forename: Donna E
authors.initials: DE
authors.lastname: Davies
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Wilson
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Holgate
authors.forename: Thomas
authors.initials: T
authors.lastname: Sandström