Histone deacetylase inhibitor, butyrate, attenuates lipopolysaccharide-induced acute lung injury in mice

<p>Abstract</p> <p>Background</p> <p>Histone deacetylase (HDAC) inhibitors, developed as promising anti-tumor drugs, exhibit their anti-inflammatory properties due to their effects on reduction of inflammatory cytokines.</p> <p>Objective</p> <p>T...

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Main Authors: Wang Yun-Jie, Zhao Jin-Bo, Tian Feng, Yan Xiao-Long, Wang Jian, Ni Yun-Feng, Jiang Tao
Format: Article
Language:English
Published: BMC 2010-03-01
Series:Respiratory Research
Online Access:http://respiratory-research.com/content/11/1/33
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author Wang Yun-Jie
Zhao Jin-Bo
Tian Feng
Yan Xiao-Long
Wang Jian
Ni Yun-Feng
Jiang Tao
author_facet Wang Yun-Jie
Zhao Jin-Bo
Tian Feng
Yan Xiao-Long
Wang Jian
Ni Yun-Feng
Jiang Tao
author_sort Wang Yun-Jie
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>Histone deacetylase (HDAC) inhibitors, developed as promising anti-tumor drugs, exhibit their anti-inflammatory properties due to their effects on reduction of inflammatory cytokines.</p> <p>Objective</p> <p>To investigate the protective effect of butyrate, a HDAC inhibitor, on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice.</p> <p>Methods</p> <p>ALI was induced in Balb/c mice by intratracheally instillation of LPS (1 mg/kg). Before 1 hour of LPS administration, the mice received butyrate (10 mg/kg) orally. The animals in each group were sacrificed at different time point after LPS administration. Pulmonary histological changes were evaluated by hematoxylin-eosin stain and lung wet/dry weight ratios were observed. Concentrations of interleukin (IL)-1β and tumor necrosis factor (TNF)-α in bronchoalveolar lavage fluid (BALF) and concentrations of nitric oxide (NO) and myeloperoxidase (MPO) activity in lung tissue homogenates were measured by enzyme-linked immunosorbent assay (ELISA). Expression of nuclear factor (NF)-κB p65 in cytoplasm and nucleus was determined by Western blot analysis respectively.</p> <p>Results</p> <p>Pretreatment with butyrate led to significant attenuation of LPS induced evident lung histopathological changes, alveolar hemorrhage, and neutrophils infiltration with evidence of reduced MPO activity. The lung wet/dry weight ratios, as an index of lung edema, were reduced by butyrate administration. Butyrate also repressed the production of TNF-α, IL-1β and NO. Furthermore, the expression of NF-κB p65 in nucleus was markedly suppressed by butyrate pretreatment.</p> <p>Conclusions</p> <p>Butyrate had a protective effect on LPS-induced ALI, which may be related to its effect on suppression of inflammatory cytokines production and NF-κB activation.</p>
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spelling doaj.art-d08e19f5a589445da7fed813f7d956892022-12-22T02:14:34ZengBMCRespiratory Research1465-99212010-03-011113310.1186/1465-9921-11-33Histone deacetylase inhibitor, butyrate, attenuates lipopolysaccharide-induced acute lung injury in miceWang Yun-JieZhao Jin-BoTian FengYan Xiao-LongWang JianNi Yun-FengJiang Tao<p>Abstract</p> <p>Background</p> <p>Histone deacetylase (HDAC) inhibitors, developed as promising anti-tumor drugs, exhibit their anti-inflammatory properties due to their effects on reduction of inflammatory cytokines.</p> <p>Objective</p> <p>To investigate the protective effect of butyrate, a HDAC inhibitor, on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice.</p> <p>Methods</p> <p>ALI was induced in Balb/c mice by intratracheally instillation of LPS (1 mg/kg). Before 1 hour of LPS administration, the mice received butyrate (10 mg/kg) orally. The animals in each group were sacrificed at different time point after LPS administration. Pulmonary histological changes were evaluated by hematoxylin-eosin stain and lung wet/dry weight ratios were observed. Concentrations of interleukin (IL)-1β and tumor necrosis factor (TNF)-α in bronchoalveolar lavage fluid (BALF) and concentrations of nitric oxide (NO) and myeloperoxidase (MPO) activity in lung tissue homogenates were measured by enzyme-linked immunosorbent assay (ELISA). Expression of nuclear factor (NF)-κB p65 in cytoplasm and nucleus was determined by Western blot analysis respectively.</p> <p>Results</p> <p>Pretreatment with butyrate led to significant attenuation of LPS induced evident lung histopathological changes, alveolar hemorrhage, and neutrophils infiltration with evidence of reduced MPO activity. The lung wet/dry weight ratios, as an index of lung edema, were reduced by butyrate administration. Butyrate also repressed the production of TNF-α, IL-1β and NO. Furthermore, the expression of NF-κB p65 in nucleus was markedly suppressed by butyrate pretreatment.</p> <p>Conclusions</p> <p>Butyrate had a protective effect on LPS-induced ALI, which may be related to its effect on suppression of inflammatory cytokines production and NF-κB activation.</p>http://respiratory-research.com/content/11/1/33
spellingShingle Wang Yun-Jie
Zhao Jin-Bo
Tian Feng
Yan Xiao-Long
Wang Jian
Ni Yun-Feng
Jiang Tao
Histone deacetylase inhibitor, butyrate, attenuates lipopolysaccharide-induced acute lung injury in mice
Respiratory Research
title Histone deacetylase inhibitor, butyrate, attenuates lipopolysaccharide-induced acute lung injury in mice
title_full Histone deacetylase inhibitor, butyrate, attenuates lipopolysaccharide-induced acute lung injury in mice
title_fullStr Histone deacetylase inhibitor, butyrate, attenuates lipopolysaccharide-induced acute lung injury in mice
title_full_unstemmed Histone deacetylase inhibitor, butyrate, attenuates lipopolysaccharide-induced acute lung injury in mice
title_short Histone deacetylase inhibitor, butyrate, attenuates lipopolysaccharide-induced acute lung injury in mice
title_sort histone deacetylase inhibitor butyrate attenuates lipopolysaccharide induced acute lung injury in mice
url http://respiratory-research.com/content/11/1/33
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