Histone deacetylase inhibitors attenuate acute lung injury during cecal ligation and puncture-induced polymicrobial sepsis.
BACKGROUND
The 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.


METHODS
Mice 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.


RESULTS
Our 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.


CONCLUSIONS
These 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.
Zhang
Li
L
Department of Pathophysiology, Laboratory of Stem Cell and Tissue Engineering, Chongqing Medical University, Chongqing, China. zhanglipp@yahoo.com.cn
Jin
Shengwei
S
Wang
Changdong
C
Jiang
Rong
R
Wan
Jingyuan
J
D000107:Acetylation / Q000187:drug effects; D055371:Acute Lung Injury / Q000097:blood / Q000150:complications / Q000453:epidemiology / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D002087:Butyrates / Q000627:therapeutic use*; D002432:Cecum / Q000601:surgery; D019040:E-Selectin / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use*; D006877:Hydroxamic Acids / Q000627:therapeutic use*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood; D008026:Ligation; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011677:Punctures; D018805:Sepsis / Q000150:complications / Q000209:etiology / Q000382:microbiology / Q000517:prevention & control*
D002087:Butyrates; D019040:E-Selectin; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D015850:Interleukin-6; D018799:Intercellular Adhesion Molecule-1; C012589:trichostatin A