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

Authors: Curtis, B. J.; Shults, J. A.; Ramirez, L; Kovacs, E. J.
Article Title: Remote Burn Injury Increases Pulmonary Histone Deacetylase 1 and Reduces Histone Acetylation
Abstract: 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% TBSA scald burn or a sham injury and killed 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.
Journal Title: Journal of burn care research : official publication of the American Burn Association
ISSN: 1559-0488; 1559-047X
Publisher: Unknown  
Date Published: 2015
Language: ENG
Notes: LR: 20151203; JID: 101262774; aheadofprint