The role of the NLRP3 Inflammasome in the pathogenesis of airway disease

被引:101
作者
Birrell, Mark A. [1 ]
Eltom, Suffwan
机构
[1] Univ London Imperial Coll Sci Technol & Med, Airway Dis Sect, Natl Heart & Lung Inst, Fac Med, London SW7 2AZ, England
基金
英国医学研究理事会; 英国生物技术与生命科学研究理事会;
关键词
Airways; COPD; Asthma; Inflammasome; NLRP3; Caspase-1; OBSTRUCTIVE PULMONARY-DISEASE; INTERLEUKIN-1 RECEPTOR ANTAGONIST; INDUCED LUNG INFLAMMATION; ASTHMA MODEL; DUST-MITE; NALP3; INFLAMMASOME; IMMUNE-RESPONSES; DENDRITIC CELLS; ALLERGIC-ASTHMA; GUINEA-PIGS;
D O I
10.1016/j.pharmthera.2011.03.007
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The incidences of respiratory diseases like asthma and Chronic Obstructive Pulmonary Disease (COPD) are increasing dramatically. Significantly, there are currently no treatments that can slow or prevent the relentless progression of COPD; and a sub-population of asthmatics are resistant to available therapies. What is more, currently prescribed medication has only minimal effect on the symptoms suffered in these patient groups. There is therefore an urgent need to develop effective drugs to treat these diseases. Whilst asthma and COPD are thought to be distinct diseases, it is currently believed that the pathogenesis of both is driven by the chronic inflammation present in the airways of these patients. It is thus hypothesised that if the inflammation could be attenuated, disease development would be slowed and symptoms reduced. It is therefore paramount to determine the pathways driving/propagating the inflammation. Recently there has been a growing body of evidence to suggest that the multimeric protein complex known as the Inflammasome may play key roles in the inflammation observed in respiratory diseases. The aim of this review is to discuss the role of the NLRP3 Inflammasome, and its associated inflammatory mediators (IL-1 beta and IL-18), in the pathogenesis of asthma and COPD. (C) 2011 Elsevier Inc. All rights reserved.
引用
收藏
页码:364 / 370
页数:7
相关论文
共 88 条
[41]   Mechanisms of release of nucleotides and integration of their action as P2X- and P2Y-receptor activating molecules [J].
Lazarowski, ER ;
Boucher, RC ;
Harden, TK .
MOLECULAR PHARMACOLOGY, 2003, 64 (04) :785-795
[42]   House dust mite regulate the lung inflammation of asthmatic mice through TLR4 pathway in airway epithelial cells [J].
Li Hongjia ;
Gai Qingling ;
Lin Meiying ;
Wang Weixuan ;
Zhang Lihong ;
Gao Yongsheng ;
Li Yanli ;
Wu Jinxiang ;
Dong Liang .
CELL BIOCHEMISTRY AND FUNCTION, 2010, 28 (07) :597-603
[43]   Extracellular Adenosine Triphosphate and Chronic Obstructive Pulmonary Disease [J].
Lommatzsch, Marek ;
Cicko, Sanja ;
Mueller, Tobias ;
Lucattelli, Monica ;
Bratke, Kai ;
Stoll, Paul ;
Grimm, Melanie ;
Duerk, Thorsten ;
Zissel, Gernot ;
Ferrari, Davide ;
Di Virgilio, Francesco ;
Sorichter, Stephan ;
Lungarella, Giuseppe ;
Virchow, J. Christian ;
Idzko, Marco .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2010, 181 (09) :928-934
[44]   The global burden of disease, 1990-2020 [J].
Lopez, AD ;
Murray, CCJL .
NATURE MEDICINE, 1998, 4 (11) :1241-1243
[45]   P2X7 Receptor Signaling in the Pathogenesis of Smoke-Induced Lung Inflammation and Emphysema [J].
Lucattelli, Monica ;
Cicko, Sanja ;
Mueller, Tobias ;
Lommatzsch, Marek ;
De Cunto, Giovanna ;
Cardini, Silvia ;
Sundas, William ;
Grimm, Melanie ;
Zeiser, Robert ;
Duerk, Thorsten ;
Zissel, Gernot ;
Sorichter, Stephan ;
Ferrari, Davide ;
Di Virgilio, Francesco ;
Virchow, J. Christian ;
Lungarella, Giuseppe ;
Idzko, Marco .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 2011, 44 (03) :423-429
[46]   Severity of elastase-induced emphysema is decreased in tumor necrosis factor-α and interleukin-1β receptor-deficient mice [J].
Lucey, EC ;
Keane, J ;
Kuang, PP ;
Snider, GL ;
Goldstein, RH .
LABORATORY INVESTIGATION, 2002, 82 (01) :79-85
[47]   House dust mite major allergen Der f 1 enhances proinflammatory cytokine and chemokine gene expression in a cell line of canine epidermal keratinocytes [J].
Maeda, Shingo ;
Maeda, Sadatoshi ;
Shibata, Sanae ;
Chimura, Naoki ;
Fukata, Tsuneo .
VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY, 2009, 131 (3-4) :298-302
[48]   Murine TLR4 is implicated in cigarette smoke-induced pulmonary inflammation [J].
Maes, Tania ;
Bracke, Ken R. ;
Vermaelen, Karim Y. ;
Demedts, Ingel K. ;
Joos, Guy F. ;
Pauwels, Romain A. ;
Brusselle, Guy G. .
INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY, 2006, 141 (04) :354-368
[49]  
Mariathasan S, 2006, NATURE, V440, P228, DOI 10.1038/nature04515
[50]   Inflammasome adaptors and sensors: intracellular regulators of infection and inflammation [J].
Mariathasan, Sanjeev ;
Monack, Denise M. .
NATURE REVIEWS IMMUNOLOGY, 2007, 7 (01) :31-40