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1 Dept of Pneumology, Clinic III for Internal Medicine, University of Cologne, Cologne, Germany and 2 Thoracic Medicine, Imperial College at National Heart & Lung Institute, London, UK
CORRESPONDENCE: A. Koch, University of Cologne, Medizinische Klinik III, Dept of Pneumology, Joseph-Stelzmann-Str. 9, 50924 Köln, Germany. Fax: 49 221 4787038 E-mail: andrea.koch@uni-koeln.de
Keywords: Cigarette smoking, extracellular signal-regulated protein kinase, human alveolar macrophages, interleukin-8, nuclear factor-
B, p38 mitogen-activated protein kinase
Received: September 15, 2003
Accepted January 26, 2004
A. Koch was supported by the Deutsche Akademie der Naturforscher Leopoldina, Halle (BMBF-LPD 9701-12); the Deutsche Forschungsgemeinschaft, Bonn (KO-1788/3-1); the Lise-Meitner-Habilitations-Program of the Ministerium für Schule, Wissenschaft und Forschung des Landes Nordrhein Westfalen, Düsseldorf (44–6037.5); and the Cologne Fortune Programme, Faculty of Medicine, University of Cologne, Cologne (project 8/2003) (all in Germany).
Inflammatory cytokine production by alveolar macrophages (AMs) is regulated by transcriptional activation and may be increased by cigarette smoking.
The smoking-induced regulation of interleukin (IL)-8 by extracellular signal-regulated kinase (ERK)-1 and -2, p38 mitogen-activated protein kinase (MAPK) and the transcription factor nuclear factor-
IL-8 production was dependent on phosphorylation of ERK-1 and -2 and p38 MAPK, as examined by PD 098059 (10 µM), an inhibitor of the upstream activator of MAPK kinase (MKK)-1, and SB 203580 (10 µM), an inhibitor of p38 MAPK. IL-8 release and the inhibitory effect of PD 098059 were increased in AMs from smokers. Moreover, ERK-2 messenger ribonucleic acid expression, as examined by reverse transcriptase polymerase chain reaction and phosphorylation of ERK-2 using Western blots, were increased in AMs from smokers, indicating a smoking-induced modulatory role of ERK-1 and -2. Lipopolysaccharide-induced IL-8 production was dependent on activation of NF-
It is concluded that cigarette smoking enhances mitogen-activated protein kinase activation more than nuclear factor-
B (NF-B) in lipopolysaccharide-stimulated AMs was assessed in nine smokers compared with nine healthy nonsmokers. B, as examined by SN 50 (100 µM), an inhibitor of NF-B translocation, and the specific NF-B inhibitor kinase-2 inhibitor, AS 602868 (10 µM), with no differences in AMs from smokers and nonsmokers. SN 50 but not PD 098059 and SB 203580 blocked NF-B deoxyribonucleic acid-binding, and this occurred to the same extent in AMs from smokers and nonsmokers, as examined by electromobility shift assay. B activation to increase lipopolysaccharide-induced interleukin-8 production in alveolar macrophages.
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