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NLRP3 Inflammasome Involves in the Acute Exacerbation of Patients with Chronic Obstructive Pulmonary Disease

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Abstract

The NLR pyrin domain-containing protein 3 (NLRP3) inflammasome, a multi-protein complex, produces the pro-inflammatory cytokines interleukin (IL)-1β and IL-18, which may contribute to the development of airway inflammation in chronic obstructive pulmonary disease (COPD). The aim of this study was to explore the correlation between circulating and local airway NLRP3 inflammasome activation with acute exacerbation of COPD (AECOPD). mRNA levels of NLRP3, Caspase (Casp)-1, apoptosis-associated speck-like protein containing CARD (ASC), IL-18, and IL-1β in peripheral blood mononuclear cells (PBMCs) and bronchial tissues were determined by real-time PCR in 32 smokers, 65 patients with AECOPD, 50 COPD patients in recovery stage, and 30 COPD patients in stable stage. The levels of IL-1β and IL-18 in serum and bronchoalveolar lavage fluid (BALF) supernatants were measured by ELISA. The load of six common pathogens in BALF samples were determined by real-time PCR. The potential correlation between the mRNA levels of NLRP3, Casp-1, ASC, IL-18 or IL-1β and the load of pathogens was evaluated individually. Significantly higher mRNA levels of NLRP3, Casp-1, ASC, IL-18, IL-1β and higher levels of IL-18 and IL-1β were found in patients with AECOPD than in smokers. These NLRP3 inflammasome mediators were significantly decreased when COPD patients in the same group became clinical stable. The increased mRNA levels of NLRP3 inflammasomes in bronchial tissues were positively correlated with the load of the six common pathogens in the lower respiratory tract. We conclude that systemic and local airway NLRP3 inflammasome activation is associated with the acute exacerbation, which might be predictive factors of the acute exacerbation and clinical outcomes in COPD patients.

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Funding

This study was funded by the Nature Scientific Fund of Ningbo City (2013A610237 and 2015A610310) and the Medical Science and Technology Project of Zhejiang Province (2017KY617), China.

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Authors and Affiliations

  1. Department of Respiratory Diseases, Affiliated Yinzhou Hospital, College of Medicine, Ningbo University, 251 East Baizhang Road, Ningbo City, 315040, Zhejiang Province, China

    Huaying Wang, Chun’er Lv, Shi Wang, Huajuan Ying & Wanjun Yu

  2. Clinical Laboratory, First Hospital, 58 Liuting Road, Ningbo City, 315010, Zhejiang Province, China

    Yuesong Weng

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  1. Huaying Wang
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  2. Chun’er Lv
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  3. Shi Wang
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Correspondence to Wanjun Yu.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the ethics and research committee of the Affiliated Yinzhou Hospital, College of Medicine, Ningbo University, China and the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Wang, H., Lv, C., Wang, S. et al. NLRP3 Inflammasome Involves in the Acute Exacerbation of Patients with Chronic Obstructive Pulmonary Disease. Inflammation 41, 1321–1333 (2018). https://doi.org/10.1007/s10753-018-0780-0

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