Activation of nuclear factor-kappaB in airway epithelial cells in patients with chronic obstructive pulmonary disease.
BACKGROUND
Chronic obstructive pulmonary disease (COPD) is characterized by chronic airway inflammation. Nuclear factor-kappaB (NF-kappaB) is a transcription factor that mediates proinflammatory gene expression. NF-kappaB is activated when its inhibitor, IkappaBalpha, is phosphorylated and degraded.


OBJECTIVE
The aims of this study were to compare the number of phosphorylated IkappaBalpha-immunopositive airway epithelial cells (AECs) in the peripheral airways of patients with COPD, asymptomatic smokers and asymptomatic nonsmokers.


METHODS
We examined lung tissues obtained from 10 smokers with COPD, 7 asymptomatic smokers and 10 asymptomatic nonsmokers. Paraffin-embedded sections and immunohistochemical techniques were used to assess the number of phosphorylated IkappaBalpha-positive AECs as well as the numbers of tumor necrosis factor (TNF)alpha-positive, 8-hydroxy-2'-deoxyguanosine (8-OHdG)-positive and 4-hydroxy-2-nonenal (4-HNE)-positive AECs in the peripheral airway specimens.


RESULTS
The percentages of phosphorylated IkappaBalpha-positive AECs and TNFalpha-positive AECs out of the total number of AECs were significantly higher in patients with COPD than in asymptomatic nonsmokers (p < 0.05). The percentage of phosphorylated IkappaBalpha-positive AECs was positively correlated with the percentage of TNFalpha-positive AECs (r = 0.82, p < 0.01), but not with the percentage of 8-OHdG-positive AECs or the percentage of 4-HNE-positive AECs.


CONCLUSIONS
The activation of NF-kappaB, which was evaluated by measuring the level of phosphorylated IkappaBalpha, was enhanced in the peripheral airway epithelia of the COPD patients in this study. The activation of NF-kappaB in the peripheral airway epithelium is associated with an elevated level of TNFalpha and seems to occur through a mechanism independent of oxidative stress.
Yagi
Osamitsu
O
First Department of Medicine, Tokyo Women's Medical University, Tokyo, Japan.
Aoshiba
Kazutetsu
K
Nagai
Atsushi
A
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000368:Aged; D000447:Aldehydes / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism* / Q000473:pathology; D020545:Respiratory Mucosa / Q000378:metabolism*; D012907:Smoking / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000447:Aldehydes; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; C027576:4-hydroxy-2-nonenal