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

Abstract:

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.

journal_name

World J Surg

journal_title

World journal of surgery

authors

Zhang L,Jin S,Wang C,Jiang R,Wan J

doi

10.1007/s00268-010-0493-5

subject

Has Abstract

pub_date

2010-07-01 00:00:00

pages

1676-83

issue

7

eissn

0364-2313

issn

1432-2323

journal_volume

34

pub_type

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