engleski

Deregulation of intracellular pathways in patients with chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a major global health problem and is predicted to become the third greatest cause of death by the year 2020. Chronic and progressive course of COPD is associated with development of local and systemic inflammation, and with oxidative stress. Cigarette smoking is the most crucial factor responsible for COPD. Oxidants found in cigarette smoke can act as direct messengers to propagate the inflammatory response through several redox-sensitive signalling molecules, such as mitogen-activated protein kinases (MAPKs), heat shock proteins (Hsps) and Bcl-2 proteins. The aim of this study was to assess the expression and activation of MAPKs (ERK, JNK, p38), and the expression of Hsps (Hsp70, Hsp27), Bcl-2 and Bax in the leukocytes of COPD patients (n = 26) and healthy volunteers (n = 43). Both patients and controls were subdivided in 3 groups: smokers, ex-smokers and non-smokers. They were all man aging mostly between 45 and 72 years. MAPK expression was unchanged regardless of health or smoking status. However, expression of Hsps, Bcl-2 and Bax proteins as well as activation of MAPKs were dependent on those parameters. Survival-enhancing ERK was not activated in COPD or healthy smokers and ex-smokers, as compared with healthy non-smokers. On the other hand, phosphorylation of stress kinases (JNK and p38) was strongly induced in COPD smokers, while the signal intensity slightly decreased in COPD ex-smokers and healthy smokers. Expression of Hsps and Bcl-2 was significantly reduced in COPD smokers and to a lesser extent in COPD ex-smokers and healthy smokers. In contrast, the Bax expression was up-regulated in all COPD patients (especially in COPD smokers) and in healthy smokers. These results show that COPD affects intracellular signalling pathways. However, the most distinguished changes were observed in smokers regardless of their health status. More research into the basic cellular and molecular mechanisms of COPD is needed to further the development of new therapies for this disease.

COPD; MAPKs; Hsps; Bcl-2

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