Diesel exhaust activates redox-sensitive transcription factors and kinases in human airways

Pourazar, Jamshid, Mudway, Ian S., Samet, James M., Helleday, Ragnberth, Blomberg, Anders, Wilson, Susan J., Frew, Anthony J., Kelly, Frank J. and Sandström, Thomas (2005) Diesel exhaust activates redox-sensitive transcription factors and kinases in human airways. American Journal of Physiology: Lung Cellular and Molecular Physiology, 289 (5), L724-L730. (doi:10.1152/ajplung.00055.2005). (PMID:16214822)

Abstract

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.

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Contributors

Author: Susan J. Wilson

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