The Journal of Immunology, 2007, 178: B55.
Copyright © 2007 by The American Association of Immunologists, Inc.
CPG potentiates the effects of cigarette smoke on releases of IL-8 in neutrophils
Esmaeil Mortaz1,
Ian Adcock2,
Kazuhiro Ito3 and
Frans P Nijkamp4
1 Pharmacology, UIPS, Sorboneelan 16, Utrecht, 3508TB, Netherlands,
2 Airways Disease Section, National Heart and Lung Institute, Imperial College London, London, UK, London, Dovehouse St, London SW3 6LY, UK, United Kingdom,
3 Imperial College London, Airways Disease Section, National Heart and Lung Institute, Dovehouse St, London SW3 6LY, London, SW3 6LY, United Kingdom,
4 pharmacology, UIPS, Sorbonnelaan 16, Utrecht, 3508TB, Netherlands
Abstract
Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. Smoking is considered the major cause of the disease. All smokers develop airway inflammation through oxidative stress with macrophages, neutrophiles and mediators (such as IL-8) involved. Previous studies have implicated a role of bacterial DNA(CpG, in the initiation of inflammation. In this study we investigated the capacity of cigarette smoke extracts (CSE) and CpG-DNA to trigger and modulate IL-8 responses in human neutrophils. A human isolated neutrophils, were exposed to the CSE, CpG, or in combination. Supernatants were isolated and analyzed for IL-8 by ELISA. The NF-B and AP-1/c-Fos activities were monitored by Western blot by using antibodies. CSE and CpG induced the release of IL-8. When co-administered release of IL-8 synergically increased which was correspondence with degradation of IB- in cytoplasm. CpG and CSE evoked concomitant increases in intracellular NO levels and consequently, nuclear accumulation of c-Fos and NF-B. Pharmacological inhibition of NF-B activity or using of N-acetylcysteine (NAC) attenuated IL-8 release. These results identify reactive oxygen dependent activation of NF-B and c-Fos as an important mechanism to CSE and CpG. In conclusion, this study show that the combination of CSE and CpG provide a substantial release of IL-8 which may accounts to exacerbation of lung in COPD patients when they are exposed to bacterium infections.
