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Inhibition of Alveolar Macrophage Pyroptosis Reduces Lipopolysaccharide-induced acute lung injury in Mice

Chinese Medical Journal 2015年第19期128卷 2638-2645页

作者： Dong-Dong Wu Pin-Hua Pan Ben Liu Xiao-Li Su Le-Meng Zhang Hong-Yi Tan ZU Cao Zuo-Ren Zhou Hai-Tao Li Hao-Si Li Li Huang Yuan-Yuan Li Department of Pulmonary and Critical Care Medicine Xiangya HospitalCentral South UniversityChangshaHunan 410008China Department of Thoracic Medicine Hunan Cancer HospitalAffiliated to Xiangya Medical SchoolCentral South UniversityChangshaHunan 410013China

Background：Pyroptosis is the term for caspase-l-dependent cell death associated with pro-inflammatory *** role of alveolar macrophage （AM） pyroptosis in the pathogenesis of the acute lung injury and acute respiratory distress syndrome （ALI/ARDS） remains ***：C57BL/6 wild-type mice were assigned to sham,lipopolysaccharide （LPS）＋ vehicle,LPS ＋ acetyl-tyrosyl-valyl-alanyl-aspartyl-chloromethylketone （Ac-YVAD-CMK） and LPS ＋ Z-Asp-Glu-Val-Asp-fluoromethylketone *** were given intraperitoneal （IP） injections of *** were IP injected 1 h before LPS *** were sacrificed 16 h after LPS administration,and AMs were *** blot analysis for active caspase-1 and cleaved caspase-3,evaluation of lung injury and a cytokine release analysis were *** were treated with LPS and adenosine triphosphate （ATP）;caspase-l-dependent cell death was evaluated using flow cytometry;the apoptosis-associated speck-like protein containing a caspase recruitment domain （ASC） pyroptosomes were examined by ***：The expression of activated caspase-1 in AMs was enhanced following LPS challenge compared with the sham *** the ex vivo study,the caspase-1/propidium iodide-positive cells,caspase-1 specks and ASC pyroptosomes were up-regulated in AMs following LPS/ATP *** specific caspase-1 inhibitor Ac-YVAD-CMK inhibited the activation of caspase-1 and pyroptotic cell ***-YVAD-CMK also reduced the lung injury,pulmonary edema and total protein in bronchoalveolar lavage fluid （BALF）.In addition,Ac-YVAD-CMK significantly inhibited interleukin-β （IL-lβ） release both in serum and BALF and reduced the levels of IL-18,tumor necrosis factor-α （TNF-α）,High Mobility Group Box 1 （HMGB1） in BALF during LPS-induced ALI/***：This study reported AM pyroptosis during LPS-induced ALI/ARDS in mice and has demonstrated that Ac-YVAD-CMK can prevent AM-induced pyroptosis and lung *** preliminary fi

关键词： acute lung injury/acute respiratory distress syndrome Alveolar Macrophage Caspase-1 Pyroptosis

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Study of low molecualr weight sulfated hyaluronic acid on the secretion of TNF-α、IL-1β from ALI/ARDS rats

Study of low molecualr weight sulfated hyaluronic acid on th...

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中国药学会全国多糖类药物研究与应用研讨会

作者： ZHANG Yun-feng Ji Sheng-li QU Lei (Institute of Biochemical and Biotechnological Drug,Schoolof Pharmacy,Shandong University,Jinan 250012)

＜正＞Objective acute lunginjury （ALI） and acute respiratory distress syndrome （ARDS） represent inflammatory processes that are initiated by diverse systemic and/or pulmonary insults,resulting in a clinical syndrome of severe respiratory distress and refractory *** and ARDS are common,life-threatening causes of acute respiratory failure that arise from a variety of local and systemic *** some improvement in mortality with a lung-protective ventilator strategy,both morbidity and mortality remain high. According to the ALI and ARDS pathogenesis studies,anti-inflammatory and anti-coagulation therapies have become important treat *** is reported that glyeosaminoglycans （GAGs） has anti-inflammatory and anti-coagulation effect in recent *** molecular weight sulfated hyaluronie acid （LMWSHA） was selected as a new anti-acute lung injury material in our *** of LMWSHA on the sectretion of TNF-α、IL-1βfrom ALI/ARDS *** LMWSHA with different molecular weights （Mr） ranges were *** tested the effects of different compositions on TNF-αand IL-1βsecreted by lung alveolus macrophage,selected the most effective *** we studied its therapeutic effects on ARDS rats,and investigated its effects on mRNA transcription of TNF-α,IL-1βin the ARDS inflammatory *** The concentration of Rat TNF-αand Rat IL-βin the supernatant of cell culture was respectively 174.88±8.84 pg/mL and 148.55±3.30 pg/mL,obviously higher than the negative control group（15.50±2.98 pg/mL,21.22±1.65 pg/mL）（P＜0.05）.Among them compositions L-1-1,B-1-1 and B-2 were the most effective *** optical density values of group L-1-1,group B-1-1 and group B-2 were found to be lower than that of the model group,and the optical density value of group L-1-1 was found to be the lowest,demonstrating that three compositions of LMWSHA have inhibitive effect on the transcription of Rat lung alveolus macrophage TNF-α,RatIL-1βmRNA,with L-1-1 being the m

关键词： Low molecular weight sulfated hyaluronic acid acute lung injury/acute respiratory distress syndrome Preparation Structure analysis Tumor necrosis factor-α Interleukin-1β mRNA

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