Erythromycin suppresses neutrophil extracellular traps in smoking-related chronic pulmonary inflammation
Erythromycin suppresses neutrophil extracellular traps in smoking-related chronic pulmonary inflammation
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红霉素抑制吸烟相关慢性肺部炎症中的中性粒细胞胞外陷阱
DOI：
10.1038/s41419-019-1909-2
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发表时间：
2019-09
影响因子：
9
通讯作者：
Zhong Xiao Ning
中科院分区：
文献类型：
--
作者：
Zhang Hui;Qiu Shi Lin;Tang Qi Ya;Zhou Xiu;Zhang Jian Quan;He Zhi Yi;Bai Jing;Li Mei Hua;Deng Jing Min;Liang Yi;Zhong Xiao Ning
神经细胞外陷阱（NETs）可能在吸烟相关的慢性气道炎症中起关键作用。然而，香烟烟雾诱导的NETs启动慢性阻塞性肺疾病（COPD）适应性免疫的机制尚未完全清楚。本研究探讨了香烟烟雾诱导的NETs对骨髓树突状细胞（mDCs）和Th1、Th17细胞的影响。此外，我们观察了红霉素对香烟烟雾诱导的NETs的抑制作用。我们发现COPD患者痰液中NET水平升高与循环Th1反应、mDC激活和气流受限相关。香烟烟雾提取物（CSE）诱导的NETs在体外可激活单核细胞来源的mDC，促进Th1和Th17细胞分化。红霉素能有效抑制CSE诱导的NET形成。在体内，红霉素减少了气道内的NET，并改善了肺气肿，使Th1和Th17细胞下调，CD40+和CD86+mDCs抑制慢性暴露于香烟烟雾的小鼠。这些发现为NET促进Th1和Th17的分化以及在吸烟相关慢性肺部炎症的适应性免疫中发挥作用提供了直接证据。红霉素是COPD中NETs抑制的潜在治疗策略。
Neutrophil extracellular traps (NETs) may play a critical role in smoking-related chronic airway inflammation. However, the mechanism by which NETs induced by cigarette smoke initiate the adaptive immunity in chronic obstructive pulmonary disease (COPD) is not fully understood. In this study, we explored the effects of NETs induced by cigarette smoke on the myeloid dendritic cells (mDCs) and Th1 and Th17 cells. Additionally, we observed the inhibitory effect of erythromycin on NETs induced by cigarette smoke. We found that elevated NET levels in the sputum of COPD patients were correlated with the circulating Th1 response, mDC activation and airflow limitation. NETs induced by cigarette smoke extract (CSE) could activate monocyte-derived mDCs and promote Th1 and Th17 differentiation in vitro. Erythromycin effectively inhibited NET formation induced by CSE. In vivo, erythromycin decreased NETs in the airway and ameliorated emphysema with Th1 and Th17 cell down-regulation and CD40+and CD86+mDCs suppression in mice chronically exposed to cigarette smoke. These findings provide direct evidence that NETs promote the differentiation of Th1 and Th17 and play a role in the adaptive immunity of smoking-related chronic lung inflammation. Erythromycin is a potential therapeutic strategy for NETs inhibition in COPD.
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DOI：
--
发表时间：
2004
期刊：
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
影响因子：
--
作者：
F. M. Moodie;John A. Marwick;Charlotte S Anderson;P. Szulakowski;S. Biswas;M. Bauter;I. Kilty;I. Rahman
通讯作者：
F. M. Moodie;John A. Marwick;Charlotte S Anderson;P. Szulakowski;S. Biswas;M. Bauter;I. Kilty;I. Rahman
影响因子：
39.3
作者：
Stakos DA;Kambas K;Konstantinidis T;Mitroulis I;Apostolidou E;Arelaki S;Tsironidou V;Giatromanolaki A;Skendros P;Konstantinides S;Ritis K
通讯作者：
Ritis K
香烟烟雾暴露通过 CD40-CD40L 共刺激途径促进小鼠 CD4( ) T 细胞向 Th17 细胞分化
DOI：
10.2147/copd.s155754
发表时间：
2018
影响因子：
2.8
作者：
Liang Y;Shen Y;Kuang L;Zhou G;Zhang L;Zhong X;Zhang J;Liu J
通讯作者：
Liu J
DOI：
10.1073/pnas.1708247114
发表时间：
2017-11-07
影响因子：
11.1
作者：
Schreiber, Adrian;Rousselle, Anthony;Kettritz, Ralph
通讯作者：
Kettritz, Ralph
DOI：
10.1016/j.jaci.2017.04.022
发表时间：
2018-01
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Dicker AJ;Crichton ML;Pumphrey EG;Cassidy AJ;Suarez-Cuartin G;Sibila O;Furrie E;Fong CJ;Ibrahim W;Brady G;Einarsson GG;Elborn JS;Schembri S;Marshall SE;Palmer CNA;Chalmers JD
通讯作者：
Chalmers JD