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- Title
Mechanism of cigarette smoke condensate-induced acute inflammatory response in human bronchial epithelial cells.
- Authors
Hellermann, Gary R.; Nagy, Szilvia B.; Xiaoyuan Kong; Lockey, Richard F.; Mohapatra, Shyam S.; Kong, Xiaoyuan
- Abstract
<bold>Background: </bold>To demonstrate the involvement of tobacco smoking in the pathophysiology of lung disease, the responses of pulmonary epithelial cells to cigarette smoke condensate (CSC) - the particulate fraction of tobacco smoke - were examined.<bold>Methods: </bold>The human alveolar epithelial cell line A549 and normal human bronchial epithelial cells (NHBEs) were exposed to 0.4 microg/ml CSC, a concentration that resulted in >90% cell survival and <5% apoptosis. Changes in gene expression and signaling responses were determined by RT-PCR, western blotting and immunocytofluorescence.<bold>Results: </bold>NHBEs exposed to CSC showed increased expression of the inflammatory mediators sICAM-1, IL-1beta, IL-8 and GM-CSF, as determined by RT-PCR. CSC-induced IL-1beta expression was reduced by PD98059, a blocker of mitogen-actived protein kinase (MAPK) kinase (MEK), and by PDTC, a NFkappaB inhibitor. Analysis of intracellular signaling pathways, using antibodies specific for phosphorylated MAPKs (extracellular signal-regulated kinase [ERK]-1/2), demonstrated an increased level of phosphorylated ERK1/2 with increasing CSC concentration. Nuclear localization of phosphorylated ERK1/2 was seen within 30 min of CSC exposure and was inhibited by PD98059. Increased phosphorylation and nuclear translocation of IkappaB was also seen after CSC exposure. A549 cells transfected with a luciferase reporter plasmid containing a NFkappaB-inducible promoter sequence and exposed to CSC (0.4 microg/ml) or TNF-alpha (50 ng/ml) had an increased reporter activity of approximately 2-fold for CSC and 3.5-fold for TNF-alpha relative to untreated controls.<bold>Conclusion: </bold>The acute phase response of NHBEs to cigarette smoke involves activation of both MAPK and NFkappaB.
- Subjects
CIGARETTE smoke; EPITHELIAL cells; INFLAMMATION; SMOKING; PROTEIN kinases
- Publication
Respiratory Research, 2002, Vol 3, p22
- ISSN
1465-9921
- Publication type
journal article