Remote Burn Injury Increases Pulmonary Histone Deacetylase 1 and Reduces Histone Acetylation

Dermal burn injury causes profound physiological derangements. Respiratory failure is a primary cause of morbidity and mortality after burn injury, in part, because of excessive and prolonged release of local and systemic proinflammatory mediators. Clinical and preclinical evidence suggests histone deacetylases (HDACs) are key mediators of inflammatory responses. The study objective was to explore the effects of dermal burn injury on pulmonary HDAC activity, identify specific lung HDAC(s) altered by burn, and characterize histone lysine acetylation status. Mice were subjected to a 15% total body surface area scald burn or a sham injury and euthanized 24 hours later. Whole lungs were harvested, or alveolar macrophages were isolated from bronchoalveolar lavage fluid. HDAC specific activity assays were performed, Western blots were run to analyze HDACs1, 2, 3, 4, and 10 or histone lysine acetylation levels, and HDAC1 and phosphorylated-HDAC1 levels and localization were examined by immunofluorescence. Burned mice had higher HDAC specific activity and increased HDAC1 levels compared with controls, but levels of other HDACs were comparable between groups. Burn injury increased levels of HDAC1 and phosphorylated-HDAC1 in bronchioles and alveolar sacs and was associated with global and specific diminished levels of histone H3 and histone H4 lysine acetylation. Our analyses reveal that pulmonary inflammation after burn injury may be modulated by epigenetic mechanisms involving HDACs ...
Source: Journal of Burn Care and Research - Category: Rehabilitation Tags: Original Articles Source Type: research