[Pathogenesis of chronic obstructive pulmonary disease. Molecular mechanisms (part II)]

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. Smoking is considered the major cause of the disease. Relatively little is known about the molecular mechanisms underlying inflammatory response in smokers' lungs and how this relates to the susceptibility to the disease, particularly why only 10-15% of smokers develop COPD. Recent development in molecular biology techniques allowed the insight into the inner space of the cell, to the levels far beyond the reach of the traditional methods. We review recent hypotheses on cellular and molecular background of COPD with emphasis on the potential role of histone acetylation, as a key modulator of enhanced gene transcription responsible for proinflammatory cytokines production in COPD. Authors propose a role for modification of nucleosomal structure in inflammatory cytokine gene transcription in response to smoking. Cigarette smoke causes oxidative stress altering the balance between histone deacetylation and acetylation in favor of acetylation. This can contribute to the airflow obstruction in smokers susceptible to the development of COPD. Furthermore, histone acetylation seems to be a potential mechanism exclusive to smokers with susceptibility to COPD based on the transcription of specific pro- and anti-inflammatory cytokine combinations.