Contribution of CFTR to alveolar fluid clearance by lipoxin A4 via PI3K/Akt pathway in LPS-induced acute lung injury.
Contribution of CFTR to alveolar fluid clearance by lipoxin A4 via PI3K/Akt pathway in LPS-induced acute lung injury.
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DOI：
10.1155/2013/862628
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发表时间：
2013
影响因子：
4.6
通讯作者：
Smith FG
中科院分区：
文献类型：
--
作者：
Yang Y;Cheng Y;Lian QQ;Yang L;Qi W;Wu DR;Zheng X;Liu YJ;Li WJ;Jin SW;Smith FG
脂质是第一个被识别并被描述为内源性炎症“制动信号”的分辨率介质。我们在脂多糖（LPS-）诱导的肺损伤模型中评估了脂素A4的抗炎和溶解生物作用。结果表明，脂素A4可显著改善大鼠肺组织学，抑制lps诱导的肺损伤中的IL-6和TNF-α。此外，脂素A4增加肺泡液清除率（AFC），并且脂素A4对AFC的影响被CFTRinh-172 （CFTR的特异性抑制剂）消除。此外，脂素A4在体外和体内均可增加囊性纤维化跨膜传导调节蛋白（CFTR）的表达。在大鼠原代肺泡II型（ATII）细胞中，LPS通过激活PI3K/Akt降低CFTR蛋白表达，脂素A4抑制LPS刺激的Akt磷酸化。这些结果表明，脂素A4通过PI3K/Akt通路增强CFTR蛋白表达，增加AFC。因此，脂素A4可能为急性肺损伤提供潜在的治疗途径。
The lipoxins are the first proresolution mediators to be recognized and described as the endogenous “braking signals” for inflammation. We evaluated the anti-inflammatory and proresolution bioactions of lipoxin A4 in our lipopolysaccharide (LPS-)induced lung injury model. We demonstrated that lipoxin A4 significantly improved histology of rat lungs and inhibited IL-6 and TNF-α in LPS-induced lung injury. In addition, lipoxin A4 increased alveolar fluid clearance (AFC) and the effect of lipoxin A4 on AFC was abolished by CFTRinh-172 (a specific inhibitor of CFTR). Moreover, lipoxin A4 could increase cystic fibrosis transmembrane conductance regulator (CFTR) protein expression in vitro and in vivo. In rat primary alveolar type II (ATII) cells, LPS decreased CFTR protein expression via activation of PI3K/Akt, and lipoxin A4 suppressed LPS-stimulated phosphorylation of Akt. These results showed that lipoxin A4 enhanced CFTR protein expression and increased AFC via PI3K/Akt pathway. Thus, lipoxin A4 may provide a potential therapeutic approach for acute lung injury.
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影响因子：
10
作者：
Perkins, G. D.;Gao, F.;Thickett, D. R.
通讯作者：
Thickett, D. R.
DOI：
10.1073/pnas.0600855103
发表时间：
2006-03-28
影响因子：
11.1
作者：
Johnson, MD;Bao, HF;Eaton, DC
通讯作者：
Eaton, DC
影响因子：
5.7
作者：
Jin, Sheng-Wei;Zhang, Li;Ye, Du-Yun
通讯作者：
Ye, Du-Yun
影响因子：
3.3
作者：
Folkesson, HG;Norlin, A;Matthay, MA
通讯作者：
Matthay, MA
DOI：
10.1165/rcmb.2007-0172oc
发表时间：
2008-02-01
影响因子：
6.4
作者：
Qiao, Renli;Yan, Weilhong;Borok, Zea
通讯作者：
Borok, Zea