Air pollution particles activate NF-kappaB on contact with airway epithelial cell surfaces.
Air pollution particles (PM) are known to elicit an acute inflammatory response in vivo that is mediated in part through PM-induced activation of the NF-kappaB signaling pathway. Many of the details of this process and particularly where in the cell it occurs are unclear. To determine whether contact of PM particles with an epithelial cell surface activates NF-kappaB, rat tracheal explants were exposed to Ottawa Urban Air Particles or iron-loaded fine TiO2, a model PM particle, for up to 2 h. During this period, there was no evidence of particle entry into the tracheal epithelial cells by light or electron microscopy, but both types of particle activated NF-kappaB as assayed by gel shifts. NF-kappaB activation could be inhibited by the active oxygen species scavenger, tetramethylthiourea; the redox-inactive metal chelator, deferoxamine; the Src inhibitor, PP2; and the epidermal growth factor (EGF) receptor inhibitor AG1478. An iron-containing citrate extract of both dusts also produced NF-kappaB activation. Both dusts and a citrate extract caused phosphorylation of the EGF receptor on tyrosine 845, an indicator of Src activity. We conclude that iron-containing PM particles can activate NF-kappaB via a pathway involving Src and the EGF receptor. This process does not require entry of particles into the airway epithelial cells but is dependent on the presence of iron and generation of active oxygen species by the dusts. These findings imply that even brief contact of PM with a pulmonary epithelial cell surface may produce deleterious effects in vivo.
Churg
Andrew
A
Department of Pathology, University of British Columbia, 2211 Wesbrook Mall, Vancouver, BC, Canada V6T 2B5. achurg@interchange.ubc.ca
Xie
Changshi
C
Wang
Xiaoshan
X
Vincent
Renaud
R
Wang
Rong D
RD
D000393:Air Pollutants / Q000032:analysis / Q000493:pharmacokinetics* / Q000633:toxicity; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D001692:Biological Transport / Q000187:drug effects; D003676:Deferoxamine / Q000494:pharmacology; D004391:Dust; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D005290:Ferric Compounds / Q000032:analysis / Q000493:pharmacokinetics / Q000633:toxicity; D016166:Free Radical Scavengers / Q000494:pharmacology; D066298:In Vitro Techniques; D016328:NF-kappa B / Q000378:metabolism*; D010316:Particle Size; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D011799:Quinazolines; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D013997:Time Factors; D014025:Titanium / Q000032:analysis / Q000493:pharmacokinetics / Q000633:toxicity; D014132:Trachea / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D020032:Tyrphostins / Q000494:pharmacology
C412373:AG 1879; D000393:Air Pollutants; D004391:Dust; D005290:Ferric Compounds; D016166:Free Radical Scavengers; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011799:Quinazolines; D020032:Tyrphostins; C009495:titanium dioxide; C101044:RTKI cpd; D014025:Titanium; D013890:Thiourea; D003676:Deferoxamine; C019107:tetramethylthiourea