Prothymosin ? overexpression contributes to the development of pulmonary emphysema.

Emphysema is one of the disease conditions that comprise chronic obstructive pulmonary disease. Prothymosin ? transgenic mice exhibit an emphysema phenotype, but the pathophysiological role of prothymosin ? in emphysema remains unclear. Here we show that prothymosin ? contributes to the pathogenesis of emphysema by increasing acetylation of histones and nuclear factor-kappaB, particularly upon cigarette smoke exposure. We find a positive correlation between prothymosin ? levels and the severity of emphysema in prothymosin ? transgenic mice and emphysema patients. Prothymosin ? overexpression increases susceptibility to cigarette smoke-induced emphysema, and cigarette smoke exposure further enhances prothymosin ? expression. We show that prothymosin ? inhibits the association of histone deacetylases with histones and nuclear factor-kappaB, and that prothymosin ? overexpression increases expression of nuclear factor-kappaB-dependent matrix metalloproteinase 2 and matrix metalloproteinase 9, which are found in the lungs of patients with chronic obstructive pulmonary disease. These results demonstrate the clinical relevance of prothymosin ? in regulating acetylation events during the pathogenesis of emphysema. [ABSTRACT FROM AUTHOR]