Increased activation of p38 MAPK in COPD.
Inflammation, oxidative stress and apoptosis, which are involved in chronic obstructive pulmonary disease (COPD) pathogenesis, may activate the p38 subgroup of mitogen-activated protein kinases (MAPKs). Therefore, the aim of the present study was to evaluate the expression of the phosphorylated, active form of p38 MAPK (phospho-p38) in the lungs of COPD patients. Surgical specimens were obtained from 18 smokers with COPD at different stages of disease severity, plus nine smoking and eight nonsmoking subjects with normal lung function. Phospho-p38+ cells were quantified by immunohistochemistry in both alveolar spaces and alveolar walls. Moreover, a Western blot analysis of phospho-p38 and total p38alpha isoform expressed by alveolar macrophages was performed. Phospho-p38+ alveolar macrophages and phospho-p38+ cells in alveolar walls were increased in patients with severe and mild/moderate COPD, compared with smoking and nonsmoking controls. Moreover, they were inversely correlated to values of forced expiratory volume in one second (FEV(1)) and FEV(1)/forced vital capacity. Western blot analysis showed that phosphorylated p38, but not the total p38alpha isoform, was specifically increased in alveolar macrophages from COPD patients. Activation of the p38 mitogen-activated protein kinase pathway appears to be involved in the pathogenesis of chronic obstructive pulmonary disease. The present findings suggest that this protein may be a suitable pharmacological target for therapeutic intervention.
Renda
T
T
Dept of Experimental and Clinical Medicine, University Magna Graecia of Catanzaro, Catanzaro, Italy.
Baraldo
S
S
Pelaia
G
G
Bazzan
E
E
Turato
G
G
Papi
A
A
Maestrelli
P
P
Maselli
R
R
Vatrella
A
A
Fabbri
L M
LM
Zuin
R
R
Marsico
S A
SA
Saetta
M
M
D000368:Aged; D017209:Apoptosis; D004789:Enzyme Activation; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008168:Lung / Q000201:enzymology / Q000473:pathology*; D016676:Macrophages, Alveolar / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D018384:Oxidative Stress; D029424:Pulmonary Disease, Chronic Obstructive / Q000201:enzymology*; D012907:Smoking; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D048051:p38 Mitogen-Activated Protein Kinases