Diesel exhaust activates redox-sensitive transcription factors and kinases in human airways.
Diesel exhaust (DE) is a major component of airborne particulate matter. In previous studies we have described the acute inflammatory response of the human airway to inhaled DE. This was characterized by neutrophil, mast cell, and lymphocyte infiltration into the bronchial mucosa with enhanced epithelial expression of IL-8, Gro-alpha, and IL-13. In the present study, we investigated whether redox-sensitive transcription factors were activated as a consequence of DE exposure, consistent with oxidative stress triggering airway inflammation. In archived biopsies from 15 healthy subjects exposed to DE [particulates with a mass median diameter of <10 mum, 300 microg/m3] and air, immunohistochemical staining was used to quantify the expression of the transcription factors NF-kappaB (p65) and AP-1 (c-jun and c-fos), as well their upstream MAPKs, p38 and JNK, in the bronchial epithelium. In addition, phosphorylation of tyrosine residues was examined. DE induced a significant increase in the nuclear translocation of NF-kappaB (P = 0.02), AP-1 (P = 0.02), phosphorylated JNK (P = 0.04), and phosphorylated p38 (P = 0.01), as well as an increase in total (cytoplasmic + nuclear) immunostaining of phosphorylated p38 (P = 0.03). A significant increase in nuclear phosphorylated tyrosine was also observed (P < 0.05). These observations demonstrate that DE activates redox-sensitive transcription factors in vivo consistent with oxidative stress triggering the increased synthesis of proinflammatory cytokines.
Pourazar
Jamshid
J
Dept. of Respiratory Medicine and Allergy, Univ. Hospital, SE-901 85 Umeå, Sweden.
Mudway
Ian S
IS
Samet
James M
JM
Helleday
Ragnberth
R
Blomberg
Anders
A
Wilson
Susan J
SJ
Frew
Anthony J
AJ
Kelly
Frank J
FJ
Sandström
Thomas
T
D000328:Adult; D000393:Air Pollutants / Q000633:toxicity*; D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D010084:Oxidation-Reduction; D011494:Protein Kinases / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D001335:Vehicle Emissions / Q000633:toxicity*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000393:Air Pollutants; D016207:Cytokines; D018836:Inflammation Mediators; D018808:Transcription Factor AP-1; D051996:Transcription Factor RelA; D014157:Transcription Factors; D001335:Vehicle Emissions; D011494:Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases