Conclusion
death, airway neutrophilia
INFLAMMATION, LYMPHOCYTOSIS, OXIDATIVE STRESS, SECONDARY
Six-hours after an acute high-dose diesel challenge, in the presence of a robust central airway neutrophilia and lymphocytosis, we observed evidence of AhR nuclear translocation/activation, associated with increased CYP1A1 expression. This occurred in the absence of Nrf2 activation/nuclear translocation. The present data therefore suggest that the acute effects of diesel exhaust in humans are likely driven by AhR ligands within the organic fraction, activating the AhR. The c-Jun activity as a redox sensitive molecule, in the absence of activated Nrf2 and inflammation, may be secondary to this, as indicated from previous observations in airway nerves [Due to the invasive nature of human studies that employ bronchoscopy, there are limitations when it comes to the number of samples that can be obtained. Therefore, the present study is limited in that it only allows a brief snap-shot in time of multiple overlapping molecular activity. There is clearly a need to obtain a better kinetic understanding of the early induction of these transcription factors and their interaction, but what the present study does imply is that the simple schema, in which inhaled combustion particles first induce oxidative stress in the lung, triggering downstream responses, ranging from adaptation to cell death, does always not seem to be operating and that the AhR, is suggested to play a central role in the early airway response to diesel exhaust. Given our previous observations of the induction of NFκB (p65) and AP-1 (phosphorylated c-jun) at this early time point [