Increased activation of p38 MAPK in chronic obstructive pulmonary disease

¹ University "Magna Græcia" of Catanzaro, Dept of Experimental and Clinical Medicine, Catanzaro, Italy; and Second University of Naples, Dept of Cardiothoracic and Respiratory Sciences, Naples, Italy
² University of Padova, Dept of Cardiac, Thoracic and Vascular Sciences, Padova, Italy
³ University "Magna Græcia" of Catanzaro, Dept of Experimental and Clinical Medicine, Catanzaro, Italy
⁴ University of Ferrara, Dept of Clinical and Experimental Medicine, Ferrara, Italy
⁵ University of Padova, Dept of Environmental Medicine and Public Health, Padova, Italy
⁶ Second University of Naples, Dept of Cardiothoracic and Respiratory Sciences, Naples, Italy
⁷ University of Modena and Reggio Emilia, Dept of Oncology, Haematology and Respiratory Disease, Modena, Italy.

^* To whom correspondence should be addressed. E-mail: marina.saetta{at}unipd.it.

	Abstract

Inflammation, oxidative stress and apoptosis, which are involved in COPD pathogenesis, may activate the p38 subgroup of mitogen-activated protein kinases (MAPK). Therefore, the aim of this study was to evaluate the expression of the phosphorylated, active form of p38 MAPK in lungs of COPD patients.

Surgical specimens were obtained from 18 smokers with COPD at different stages of disease severity, 9 smoking and 8 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 phosphorylated p38 and total p38 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 when compared with smoking and nonsmoking controls. Moreover, they were inversely correlated to values of FEV₁ and FEV₁/FVC. Western blot analysis showed that phosphorylated p38, but not the total isoform, was specifically increased in alveolar macrophages from COPD patients.

Activation of the p38 MAPK pathway appears to be involved in the pathogenesis of COPD. Therefore, our findings suggest that this MAPK may be a suitable pharmacologic target for therapeutic intervention in COPD.

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