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 because HDAC activity, HDAC1 expression and activity, and downstream
histone acetylation were all altered after
burn. Future studies will explore the role of
HDAC inhibitors in reversing inflammatory defects and may ultimately lead to new treatment interventions for
burn patients.