TIPE2 ameliorates lipopolysaccharide-induced apoptosis and inflammation in acute lung injury
TIPE2 ameliorates lipopolysaccharide-induced apoptosis and inflammation in acute lung injury
复制标题
TIPE2 改善急性肺损伤中脂多糖诱导的细胞凋亡和炎症
DOI：
10.1007/s00011-019-01280-6
复制
发表时间：
2019-11-01
影响因子：
6.7
通讯作者：
Song, Xuemin
中科院分区：
文献类型：
--
作者：
Wu, Xiaojing;Kong, Qian;Song, Xuemin
目的肿瘤坏死因子α诱导蛋白8样2（Tumour necrosis factor-alpha-induced protein 8-like 2，TIPE 2）具有较强的抗炎作用。然而，尚不清楚增加的TIPE 2是否对脂多糖（LPS）诱导的ALI具有保护作用。在目前的研究中，我们的目的是调查是否增加TIPE 2可以发挥保护作用，在小鼠模型中的ALI由LPS.Methods我们管理TIPE 2腺相关病毒（AAV-TIPE 2）intrichially到小鼠的肺。3周后，BALB/c小鼠腹腔内注射LPS诱导ALI。24 h后，取肺支气管肺泡灌洗液（BALF）分析细胞和蛋白，采集动脉血进行动脉血气分析和促炎因子水平测定，并收集肺组织进行组织学检查、透射电镜（TEM）、TUNEL染色、湿/干（W/D）重量比分析，结果TIPE 2过表达可明显减轻LPS诱导的肺损伤，并可减轻肺组织病理学改变、组织学评分、BALF中W/D重量比和总蛋白表达。此外，TIPE 2过表达显著减弱肺部炎症，如BALF中多形核中性粒细胞（PMN）、肺MPO活性和血清中促炎细胞因子水平的下调所证明的。此外，TIPE 2过表达不仅显着地阻止LPS诱导的小鼠肺细胞凋亡，但也阻断LPS激活的JNK磷酸化和NF-κ B p65 nucleartranslocation.Conclusions我们的研究表明，在小鼠肺中的AAV介导的TIPE 2的表达增加抑制急性炎症和凋亡，并抑制NF-κ B和JNK的激活在小鼠模型的ALI。
Objective Tumour necrosis factor-alpha-induced protein 8-like 2 (TIPE2) has strong anti-inflammatory properties. However, it is unknown whether increased TIPE2 is protective against lipopolysaccharide (LPS)-induced ALI. In the current study, we aimed to investigate whether increased TIPE2 can exert protective effects in a mouse model of ALI induced by LPS.Methods We administered TIPE2 adeno-associated virus (AAV-TIPE2) intratracheally into the lungs of mice. Three weeks later, ALI was induced by intratracheal injection of LPS into BALB/c mice. Twenty-four hours later, lung bronchoalveolar lavage fluid (BALF) was acquired to analyse cells and protein, arterial blood was collected for arterial blood gas analysis and the determination of pro-inflammatory factor levels, and lung issues were collected for histologic examination, transmission electron microscopy (TEM), TUNEL staining, wet/dry (W/D) weight ratio analysis, myeloperoxidase (MPO) activity analysis and blot analysis of protein expression.Results We found that TIPE2 overexpression markedly mitigated LPS-induced lung injury, which was evaluated by the deterioration of histopathology, histologic scores, the W/D weight ratio, and total protein expression in the BALF. Moreover, TIPE2 overexpression markedly attenuated lung inflammation, as evidenced by the downregulation of polymorphonuclear neutrophils (PMNs) in the BALF, lung MPO activity, and pro-inflammatory cytokine levels in the serum. Moreover, TIPE2 overexpression not only dramatically prevented LPS-induced pulmonary cell apoptosis in mice but also blocked LPS-activated JNK phosphorylation and NF-kappa B p65 nuclear translocation.Conclusions Our study shows that the increased expression of AAV-mediated TIPE2 in the lungs of mice inhibits acute inflammation and apoptosis and suppresses the activation of NF-kappa B and JNK in a murine model of ALI.