TNF-α Is a Key Regulator of MUC1, an Anti-inflammatory Molecule, during Airway Pseudomonas aeruginosa Infection
TNF-α Is a Key Regulator of MUC1, an Anti-inflammatory Molecule, during Airway Pseudomonas aeruginosa Infection
复制标题
DOI：
10.1165/rcmb.2009-0323oc
复制
发表时间：
2011-02-01
影响因子：
6.4
通讯作者：
Kim, Kwang Chul
中科院分区：
文献类型：
--
作者：
Choi, Seongwon;Park, Yong Sung;Kim, Kwang Chul
MUC1是一种异源二聚体粘蛋白，表达于呼吸道上皮细胞和造血细胞的顶端表面。体内和体外研究表明，MUC1可抑制铜绿假单胞菌(PA)诱导的炎症反应。在这项研究中，我们试图利用完整的动物(C57BL/6小鼠)来确定MUC1的表达在呼吸道PA感染过程中是否重要，以及在炎症过程中MUC1水平是如何控制的。结果表明：(1)野生型(WT)组小鼠肺泡灌洗液中MUC1的水平最初较低，吸入PA后逐渐升高，第2天达高峰，第4天持续升高，第7天逐渐下降至基础水平；(2)PA感染后，肿瘤坏死因子受体1(-/-)小鼠的肺泡灌洗液中MUC1水平无明显升高；(3)吸入PA后，无论是MUC1(-/-)组还是TNF受体(-/-)组小鼠的支气管肺泡灌洗液中均有较多的炎性细胞；(4)WT组小鼠肺泡灌洗液中中性粒细胞凋亡率明显高于MUC1(-/-)组。我们的结论是，在PA呼吸道感染期间，MUC1(-/-)小鼠比WT小鼠更具炎症性，这是由于中性粒细胞内流增加和中性粒细胞凋亡减少所致。这些结果提示，PA感染过程中MUC1的上调可能是抑制过度和持久的炎症反应的关键，并且主要由关键的促炎介质--肿瘤坏死因子-α诱导。
Muc1 is a heterodimeric mucin that is expressed on the apical surface of airway epithelial cells as well as hematopoietic cells. Both in vivo and in vitro studies revealed that Muc1 suppresses inflammatory responses induced by Pseudomonas aeruginosa (PA). In this study, we sought to determine, using intact animals (C57BL/6 mice), whether the expression of Muc1 is important during airway PA infection, and how Muc1 levels are controlled during inflammation. Our results showed that: (1) Muc1 levels in the wild-type (WT) mice were initially low, but gradually increased after PA inhalation, reaching a peak on Day2, remaining elevated until Day4, and then gradually decreasing to basal levels on Day 7; (2) TNF receptor 1(-/-) mice failed to increase Muc1 levels after PA infection; (3) after PA inhalation, more inflammatory cells were present in the bronchoalveolar lavage fluid from either Muc1(-/-) or TNF receptor(-/-) mice compared with their WT control animals; (4) more apoptotic neutrophils were present in bronchoalveolar lavage fluid from WT mice compared with Muc1(-/-) mice. We conclude that Muc1(-/-) mice are more inflammatory than WT mice during airway PA infection as a result of both an increase in neutrophil influx and a decrease in neutrophil apoptosis. These results suggest that the up-regulation of Muc1 during airway PA infection might be crucial for suppressing excessive and prolonged inflammatory responses, and is induced mainly by TNF-alpha, the key proinflammatory mediator.