The NLRP3 inflammasome is critically involved in the development of bronchopulmonary dysplasia.
The NLRP3 inflammasome is critically involved in the development of bronchopulmonary dysplasia.
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DOI：
10.1038/ncomms9977
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发表时间：
2015-11-27
影响因子：
16.6
通讯作者：
Savani RC
中科院分区：
文献类型：
--
作者：
Liao J;Kapadia VS;Brown LS;Cheong N;Longoria C;Mija D;Ramgopal M;Mirpuri J;McCurnin DC;Savani RC
支气管肺发育不良（BPD）是早产儿的一种毁灭性肺部疾病，其发病机制包括炎症，其机制尚未完全确定。在这里，我们报告NLRP 3炎性体的激活与BPD的发展有关。高氧暴露的新生小鼠具有增加的半胱天冬酶-1活化、IL 1 β和炎症，以及减少的肺泡化。Nlrp 3 −/−小鼠没有caspase-1活性，没有IL 1 β，没有炎症反应，并经历正常的肺泡化。用IL 1受体拮抗剂阻断IL 1 β或格列本脲阻断Nlrp 3炎性体治疗高氧暴露小鼠，导致炎症减少和肺泡化增加。通气的早产狒狒显示NLRP 3炎性小体的活化，IL 1 β：IL 1 ra比率增加。早产儿呼吸衰竭气管吸出物中IL 1 β：IL 1 ra比值可预测BPD的发生。我们的结论是NLRP 3炎性体的早期激活是BPD发展的关键机制，并代表了BPD的新治疗靶点。
The pathogenesis of bronchopulmonary dysplasia (BPD), a devastating lung disease in preterm infants, includes inflammation, the mechanisms of which are not fully characterized. Here we report that the activation of the NLRP3 inflammasome is associated with the development of BPD. Hyperoxia-exposed neonatal mice have increased caspase-1 activation, IL1β and inflammation, and decreased alveolarization. Nlrp3−/− mice have no caspase-1 activity, no IL1β, no inflammatory response and undergo normal alveolarization. Treatment of hyperoxia-exposed mice with either IL1 receptor antagonist to block IL1β or glyburide to block the Nlrp3 inflammasome results in decreased inflammation and increased alveolarization. Ventilated preterm baboons show activation of the NLRP3 inflammasome with increased IL1β: IL1ra ratio. The IL1β:IL1ra ratio in tracheal aspirates from preterm infants with respiratory failure is predictive of the development of BPD. We conclude that early activation of the NLRP3 inflammasome is a key mechanism in the development of BPD, and represents a novel therapeutic target for BPD.
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影响因子：
5.5
作者：
Fukumoto, Jutaro;Fukumoto, Itsuko;Kolliputi, Narasaiah
通讯作者：
Kolliputi, Narasaiah
影响因子：
10
作者：
COONEY, TP;THURLBECK, WM
通讯作者：
THURLBECK, WM
DOI：
10.1002/bdra.23220
发表时间：
2014-03-01
影响因子：
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作者：
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通讯作者：
Bhandari, Vineet
DOI：
10.1165/rcmb.2006-0116oc
发表时间：
2007-01-01
影响因子：
6.4
作者：
Bry, Kristina;Whitsett, Jeffrey A.;Lappalainen, Urpo
通讯作者：
Lappalainen, Urpo
影响因子：
3.6
作者：
Jobe AH
通讯作者：
Jobe AH