CFTR regulates acute inflammatory responses in macrophages.
CFTR regulates acute inflammatory responses in macrophages.
复制标题
CFTR 调节巨噬细胞的急性炎症反应。
DOI：
10.1093/qjmed/hcv067
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发表时间：
2015-12
期刊：
影响因子：
--
通讯作者：
Xiao Su
中科院分区：
文献类型：
--
作者：
Zhaowei Gao;Xiao Su
背景
囊性纤维化(CF)患者呼吸道上皮细胞跨膜传导调节因子(CFTR)基因突变可导致复发的气道炎症。中性粒细胞CFTR功能障碍可能参与了内毒素诱导的急性肺炎症。CFTR缺陷还可促进血小板聚集和中性粒细胞-血小板相互作用，促进炎症反应。
目标
目的：研究肺泡巨噬细胞(AM)和腹膜巨噬细胞(PM)中CFTR的抑制或突变是否会促进其促炎反应，以及CFTR功能障碍是否会加重急性大肠杆菌诱导的肺或腹膜炎症。
设计
实验室研究。
方法
用ELISA法检测在内毒素刺激下CFTR抑制或突变的巨噬细胞产生促炎细胞因子的情况。肺或腹膜灌洗以分析促炎参数和细胞分化。测定过量肺水和肺血管通透性，以评估急性肺炎症的严重程度。
结果
大肠杆菌脂多糖模拟肺泡巨噬细胞CFTR的表达。AM和PM中cftR基因的抑制或突变均可促进肿瘤坏死因子-α和巨噬细胞炎性蛋白-2的产生。巨噬细胞CFTR突变通过核因子-kB和p38MAPK增加细胞因子的产生。用MalH2或CFTRinh-172抑制CFTR可加重大肠杆菌引起的急性肺炎症。在大肠杆菌肺炎和腹膜炎小鼠模型中，CFTR缺乏促进单核细胞和中性粒细胞的迁移。
结论
肺泡巨噬细胞或腹膜巨噬细胞表达的CFTR调节急性促炎反应。
BACKGROUND
Mutation of cystic fibrosis transmembrane conductance regulator (CFTR) in the airway epithelial cells can lead to recurrent airway inflammation in cystic fibrosis (CF). Dysfunction of CFTR in neutrophils could contribute to LPS-induced acute lung inflammation. Deficiency of CFTR could also facilitate platelet aggregation and neutrophil-platelet interaction and promote inflammation.
AIM
To study whether inhibition or mutation of CFTR in alveolar macrophages (AMs) or peritoneal macrophages (PMs) would promote their proinflammatory responses and whether dysfunction of CFTR would deteriorate acute E. coli-induced lung or peritoneal inflammation.
DESIGN
Laboratory study.
METHODS
ELISA was used to determine production of proinflammatory cytokines in the CFTR inhibited or mutated macrophages under LPS challenge. Lung or peritoneum lavage was used to analyze proinflammatory parameters and cell differentiation. Excess lung water and lung vascular permeability were measured for evaluating severity of acute lung inflammation.
RESULTS
Escherichia coli LPS simulation in AMs increased CFTR expression. Inhibition or mutation of CFTR in both AMs and PMs enhanced production of tumor necrosis factor alpha (TNF-α) and macrophage inflammatory protein-2 (MIP-2). Mutation of CFTR in macrophages exaggerated production of cytokines through NF-kB and p38 MAPK. Inhibition of CFTR by MalH2 or CFTRinh-172 deteriorates E. coli-induced acute lung inflammation. Deficiency of CFTR promotes migration of monocytes and neutrophils in E. coli pneumonia and peritonitis mouse models.
CONCLUSIONS
CFTR expressed by alveolar or peritoneal macrophages regulates acute proinflammatory responses.
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DOI：
10.4049/jimmunol.0901808
发表时间：
2010-01-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Su X;Matthay MA;Malik AB
通讯作者：
Malik AB
DOI：
10.1164/rccm.200506-917oc
发表时间：
2006-02-01
影响因子：
24.7
作者：
van Heeckeren, AM;Schluchter, MD;Davis, PB
通讯作者：
Davis, PB
DOI：
10.1164/ajrccm.163.1.9909034
发表时间：
2001-01-01
影响因子：
24.7
作者：
Matute-Bello, G;Frevert, CW;Martin, TR
通讯作者：
Martin, TR
DOI：
10.1152/ajplung.2001.281.1.l71
发表时间：
2001-07
期刊：
American journal of physiology. Lung cellular and molecular physiology
影响因子：
--
作者：
Audrey J. Weber;Grace Soong;Ruth Bryan;Shahryar Saba;Alice Prince
通讯作者：
Audrey J. Weber;Grace Soong;Ruth Bryan;Shahryar Saba;Alice Prince
影响因子：
8.3
作者：
Mogayzel, Peter J Jr;Naureckas, Edward T;Marshall, Bruce C
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Marshall, Bruce C