• Li Zhang, Shengwei Jin, Changdong Wang, Rong Jiang, and Jingyuan Wan.
• Department of Pathophysiology, Laboratory of Stem Cell and Tissue Engineering, Chongqing Medical University, Chongqing, China. zhanglipp@yahoo.com.cn
• World J Surg. 2010 Jul 1;34(7):1676-83.

BackgroundThe histone deacetylase (HDAC) inhibitors have emerged as the useful reagents that epigenetically modulate the expression of various genes. In the present study, the effects of HDAC inhibitors on the expression of inflammation-related genes and lung injury during sepsis were investigated.MethodsMice were pretreated with two structurally unrelated HDAC inhibitors, Trichostatin A (TSA) and sodium butyrate (SB). Thirty minutes later, mice underwent cecal ligation and puncture (CLP)-induced sepsis. Lung injury and the expression of inflammation-related molecules were determined. In addition, survival was assessed post-CLP.ResultsOur results indicated that administration of TSA or SB alleviated sepsis-induced lung injury. This was accompanied by reduced neutrophil infiltration, decreased intercellular adhesion molecule-1 (ICAM-1) and E-selectin expression in lung tissue, and lower interleukin-6 (IL-6) level in plasma. In addition, treatment with HDAC inhibitors significantly prolonged the survival time of CLP mice.ConclusionsThese data indicated that the HDAC inhibitors, based on modulating the key enzymes linked to acetylation modification, effectively attenuate intrapulmonary inflammatory response, thus significantly alleviating lung injury during sepsis.

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