IL-17 Aggravates Pseudomonas aeruginosa Airway Infection in Acute Exacerbations of Chronic Obstructive Pulmonary Disease.
IL-17 Aggravates Pseudomonas aeruginosa Airway Infection in Acute Exacerbations of Chronic Obstructive Pulmonary Disease.
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IL-17 在慢性阻塞性肺疾病急性加重中加重铜绿假单胞菌气道感染
DOI：
10.3389/fimmu.2021.811803
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发表时间：
2021
影响因子：
7.3
通讯作者：
Zhang M
中科院分区：
文献类型：
--
作者：
Ding F;Han L;Fu Q;Fan X;Tang R;Lv C;Xue Y;Tian X;Zhang M
铜绿假单胞菌气道感染会增加慢性阻塞性肺疾病（COPD）急性加重及死亡风险。我们旨在阐明白细胞介素 - 17（IL - 17）在其发病机制中的作用。我们检测了稳定期COPD患者（n = 33）以及因铜绿假单胞菌感染导致COPD急性加重患者（n = 34）体内IL - 23/IL - 17A的表达情况及其影响。利用COPD小鼠模型（C57BL / 6），通过应用IL - 17A中和抗体或重组IL - 17A，研究IL - 17A在宿主针对铜绿假单胞菌感染的炎症反应中的作用。我们发现，铜绿假单胞菌感染会增强COPD患者及COPD小鼠模型肺部的IL - 23/17A信号传导。当使用针对IL - 17A的中和抗体处理COPD小鼠模型时，与未处理的对照组相比，铜绿假单胞菌诱导的肺部多形核白细胞浸润显著减少，细菌载量也降低。中和抗体还改善了肺功能。此外，阻断IL - 17A信号传导可显著降低促炎细胞因子IL - 1β、IL - 18、肿瘤坏死因子 - α（TNF - α）、趋化因子CXCL1、CXCL15和基质金属蛋白酶 - 9（MMP - 9）的表达，并增加抗炎细胞因子IL - 10和IL - 1受体拮抗剂（IL - 1Ra）的表达。在COPD小鼠模型中应用小鼠重组IL - 17A会加剧铜绿假单胞菌介导的炎症反应和肺功能障碍。细胞因子蛋白芯片显示，IL - 17A可下调视黄醇结合蛋白4（RBP4）的表达，而外源性RBP4重组蛋白可减轻铜绿假单胞菌诱导的气道功能障碍的严重程度。在COPD小鼠模型接种铜绿假单胞菌后，同时应用IL - 17A中和抗体和环丙沙星可减轻气道炎症和改善通气。我们的研究结果表明，IL - 17在COPD急性加重期铜绿假单胞菌气道感染的发病机制中起有害作用。靶向IL - 17A是控制COPD患者铜绿假单胞菌感染结局的一种潜在治疗策略。
Pseudomonas aeruginosa airway infection increases risks of exacerbations and mortality in chronic obstructive pulmonary disease (COPD). We aimed to elucidate the role of IL-17 in the pathogenesis. We examined the expression and influences of IL-23/IL-17A in patients with stable COPD (n = 33) or acute COPD exacerbations with P. aeruginosa infection (n = 34). A mouse model of COPD (C57BL/6) was used to investigate the role of IL-17A in host inflammatory responses against P. aeruginosa infection through the application of IL-17A–neutralizing antibody or recombinant IL-17A. We found that P. aeruginosa infection increased IL-23/17A signaling in lungs of both COPD patients and COPD mouse models. When COPD mouse models were treated with neutralizing antibody targeting IL-17A, P. aeruginosa induced a significantly less polymorphonuclear leukocyte infiltration and less bacterial burden in their lungs compared to those of untreated counterparts. The lung function was also improved by neutralizing antibody. Furthermore, IL-17A-signaling blockade significantly reduced the expression of pro-inflammatory cytokine IL-1β, IL-18, TNF-α, CXCL1, CXCL15 and MMP-9, and increased the expression of anti-inflammatory cytokine IL-10 and IL-1Ra. The application of mouse recombinant IL-17A exacerbated P. aeruginosa-mediated inflammatory responses and pulmonary dysfunction in COPD mouse models. A cytokine protein array revealed that the expression of retinol binding protein 4 (RBP4) was down-regulated by IL-17A, and exogenous RBP4-recombinant protein resulted in a decrease in the severity of P. aeruginosa-induced airway dysfunction. Concurrent application of IL-17A-neutralizing antibody and ciprofloxacin attenuated airway inflammation and ventilation after inoculation of P. aeruginosa in COPD mouse models. Our results revealed that IL-17 plays a detrimental role in the pathogenesis of P. aeruginosa airway infection during acute exacerbations of COPD. Targeting IL-17A is a potential therapeutic strategy in controlling the outcomes of P. aeruginosa infection in COPD patients.
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影响因子：
13.2
作者：
Jin, Wei;Dong, Chen
通讯作者：
Dong, Chen
影响因子：
8.7
作者：
Dinarello CA
通讯作者：
Dinarello CA
影响因子：
7.5
作者：
Lode, H.;Allewelt, M.;Schmidt-Ioanas, M.
通讯作者：
Schmidt-Ioanas, M.
DOI：
10.1073/pnas.0605200103
发表时间：
2006-08-15
影响因子：
11.1
作者：
Feuillet, Vincent;Medjane, Samir;Alexopoulou, Lena
通讯作者：
Alexopoulou, Lena
影响因子：
15.9
作者：
Cohen, Taylor S.;Prince, Alice S.
通讯作者：
Prince, Alice S.