Influenza a virus triggers acute exacerbation of chronic obstructive pulmonary disease by increasing proinflammatory cytokines secretion via NLRP3 inflammasome activation.
Influenza a virus triggers acute exacerbation of chronic obstructive pulmonary disease by increasing proinflammatory cytokines secretion via NLRP3 inflammasome activation.
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甲型流感病毒通过 NLRP3 炎性体激活增加促炎细胞因子的分泌，从而引发慢性阻塞性肺疾病的急性加重
DOI：
10.1186/s12950-022-00305-y
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发表时间：
2022-06-23
影响因子：
5.1
通讯作者：
Fei, Guang-He
中科院分区：
文献类型：
--
作者：
Ji, Shuang;Dai, Meng-Yuan;Huang, Yun;Ren, Xiang-Chun;Jiang, Meng-Long;Qiao, Jin-Ping;Zhang, Wen-Ying;Xu, Yuan-Hong;Shen, Ji-Long;Zhang, Ren-Quan;Fei, Guang-He
关键词：
研究背景甲型流感病毒（Influenza A virus，IAV）可引起慢性阻塞性肺疾病（Chronic Obstructive Pulmonary Disease，AECOPD）急性加重，但其分子机制尚不清楚。在这项研究中，我们研究了IAV诱导的NLRP 3炎性小体激活，以增加气道炎症反应的进展AECOPD.MethodsHuman支气管上皮细胞分离和培养正常和COPD支气管组织和共培养IAV的作用。RNA测序鉴定NLRP 3炎性小体相关基因，qRT-PCR和western blot检测siRNA转染细胞和MCC 950处理后NLRP 3炎性小体组分的表达。建立IAV诱导的COPD大鼠模型，检测37例AECOPD患者血清和支气管肺泡灌洗液（BALF）中IL-18和IL-1β的含量。然而，两个细胞组在接种后12小时达到峰值NLRP 3水平，并将其维持长达24小时。ASC、Caspase-1、IL-1β和IL-18在两个细胞组中也以相似的时间依赖性模式升高。当用siRNA和MCC 950处理COPD细胞时，NLRP 3炎性体组分的mRNA和蛋白表达降低。在COPD大鼠中，NLRP 3炎性体组分被IAV升高。MCC 950可减轻COPD大鼠肺损伤，延长生存时间，降低NLRP 3炎性体成分的表达。结论NLRP 3炎性小体在COPD患者中作为一种预先存在的疾病被激活，IAV感染进一步加重了COPD患者的病情。
BackgroundInfluenza A virus (IAV) triggers acute exacerbation of chronic obstructive pulmonary disease (AECOPD), but the molecular mechanisms remain unclear. In this study, we investigated the role of IAV induced NLRP3 inflammasome activation to increase airway inflammation response in the progression of AECOPD.MethodsHuman bronchial epithelial cells were isolated and cultured from normal and COPD bronchial tissues and co-cultured with IAV. The NLRP3 inflammasome associated genes were identified using RNA sequencing, and the expressions of NLRP3 inflammasome components were measured using qRT-PCR and western blot after cells were transfected with siRNA and treated with MCC950. Moreover, IAV-induced COPD rat models were established to confirm the results; 37 AECOPD patients were included to measure the serum and bronchoalveolar lavage fluid (BALF) of interleukin (IL)-18 and IL-1β.ResultsIncreased levels of NLRP3 inflammasome components were not seen until 6 h post-inoculation in normal cells. However, both cell groups reached peak NLRP3 level at 12 h post-inoculation and maintained it for up to 24 h. ASC, Caspase-1, IL-1β and IL-18 were also elevated in a similar time-dependent pattern in both cell groups. The mRNA and protein expression of the NLRP3 inflammasome components were decreased when COPD cells treated with siRNA and MCC950. In COPD rats, the NLRP3 inflammasome components were elevated by IAV. MCC950 alleviated lung damage, improved survival time, and reduced NLRP3 inflammasome components expression in COPD rats. Additionally, the serum and BALF levels of IL-1β and IL-18 were increased in AECOPD patients.ConclusionsNLRP3 inflammasome is activated in COPD patients as a pre-existing condition that is further exacerbated by IAV infection.
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DOI：
10.1038/nri3665
发表时间：
2014-05
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
6.7
作者：
McAuley JL;Tate MD;MacKenzie-Kludas CJ;Pinar A;Zeng W;Stutz A;Latz E;Brown LE;Mansell A
通讯作者：
Mansell A
使用雷帕霉素和 MK-2206 联合靶向 mTOR 和 Akt 治疗结节性硬化症
影响因子：
3.9
作者：
Ji S;Lin W;Wang L;Ni Z;Jin F;Zha X;Fei G
通讯作者：
Fei G
影响因子：
24.3
作者：
Herold, Susanne;Becker, Christin;Budinger, G. R. Scott
通讯作者：
Budinger, G. R. Scott
影响因子：
15.3
作者：
Ichinohe, Takeshi;Lee, Heung Kyu;Ogura, Yasunori;Flavell, Richard;Iwasaki, Akiko
通讯作者：
Iwasaki, Akiko