Targeting the NF-κB pathway in asthma and chronic obstructive pulmonary disease

被引:335
作者
Edwards, Michael R. [1 ,2 ,3 ,4 ,5 ]
Bartlett, Nathan W. [1 ,2 ,3 ,4 ,5 ]
Clarke, Deborah [5 ]
Birrell, Mark [5 ]
Belvisi, Maria [5 ]
Johnston, Sebastian L. [1 ,2 ,3 ,4 ,5 ]
机构
[1] Univ London Imperial Coll Sci Technol & Med, Natl Heart Lung Inst, Dept Resp Med, London W1 2PG, England
[2] Univ London Imperial Coll Sci Technol & Med, Natl Heart Lung Inst, Wright Fleming Inst Infect & Immun, London W1 2PG, England
[3] MRC, London, England
[4] Asthma UK Ctr Allerg Mech Asthma, London, England
[5] Ctr Resp Infect, London, England
基金
英国生物技术与生命科学研究理事会;
关键词
NF-kB; IKK-beta; Asthma; COPD; Inflammation; Lung; NECROSIS-FACTOR-ALPHA; BRONCHIAL EPITHELIAL-CELLS; AIRWAY SMOOTH-MUSCLE; TRANSCRIPTION FACTOR DECOY; ADENOVIRAL-MEDIATED DELIVERY; DOUBLE-STRANDED-RNA; GLUCOCORTICOID-RECEPTOR; GENE-EXPRESSION; TNF-ALPHA; IKK-BETA;
D O I
10.1016/j.pharmthera.2008.09.003
中图分类号
R9 [药学];
学科分类号
100702 [药剂学];
摘要
Asthma and chronic obstructive pulmonary disease are inflammatory lung disorders responsible for significant morbidity and mortality worldwide. While the importance of allergic responses in asthma is well known, respiratory viral and bacterial infections and pollutants especially cigarette smoke are important factors in the pathogenesis of both diseases. Corticosteroid treatment remains the first preference of treatment in either disease, however these therapies are not always completely effective, and are associated with side effects and steroid resistance. Due to such limitations, development of new treatments represents a major goal for both the pharmaceutical industry and academic researchers. There are now excellent reasons to promote NF-kB signalling intermediates and Rel family proteins as potential therapeutic targets for both asthma and chronic obstructive pulmonary disease. This notion is supported by the fact that much of the underlying inflammation of both diseases independent of stimuli, is mediated at least in part, by NF-kB mediated signalling events in several cell types. Also, a range of inhibitors of NF-kB signalling intermediates are now available, including DNA oligonucleotides and DNA-peptide molecules that act as NF-kB decoy sequences, small molecule inhibitors such as IKK-beta inhibitors, and proteasome inhibitors affecting NF-kB signalling, that have either shown promise in animal models or have begun clinical trials in other disorders. This review will focus on the role of NF-kB in both diseases. will discuss its suitability as a target, and will highlight recent key studies that support the potential of NF-kB as a therapeutic target in these two important inflammatory lung diseases. (c) 2008 Elsevier Inc. All rights reserved.
引用
收藏
页码:1 / 13
页数:13
相关论文
共 213 条
[1]
ABNORMAL GLUCOCORTICOID RECEPTOR ACTIVATOR PROTEIN-1 INTERACTION IN STEROID-RESISTANT ASTHMA [J].
ADCOCK, IM ;
LANE, SJ ;
BROWN, CR ;
LEE, TH ;
BARNES, PJ .
JOURNAL OF EXPERIMENTAL MEDICINE, 1995, 182 (06) :1951-1958
[2]
ADCOCK IM, 1995, J IMMUNOL, V154, P3500
[3]
Alexander JH, 2005, JAMA-J AM MED ASSOC, V294, P2446
[4]
Worldwide time trends in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in childhood:: ISAAC Phases One and Three repeat multicountry cross-sectional surveys [J].
Asher, M. Innes ;
Montefort, Stephen ;
Bjorksten, Bengt ;
Lai, Christopher K. W. ;
Strachan, David P. ;
Weiland, Stephan K. ;
Williams, Hywel .
LANCET, 2006, 368 (9537) :733-743
[5]
Toll-like receptor stimulation induces airway hyper-responsiveness to bradykinin, an effect mediated by JNK and NF-κB signaling pathways [J].
Bachar, O ;
Adner, M ;
Uddman, R ;
Cardell, LO .
EUROPEAN JOURNAL OF IMMUNOLOGY, 2004, 34 (04) :1196-1207
[6]
The transcription factor NF-κB and human disease [J].
Baldwin, AS .
JOURNAL OF CLINICAL INVESTIGATION, 2001, 107 (01) :3-6
[7]
EPIDEMIOLOGY AND TREATMENT OF CHRONIC-BRONCHITIS AND ITS EXACERBATIONS [J].
BALL, P .
CHEST, 1995, 108 (02) :S43-S52
[8]
Neutrophilic infiltration within the airway smooth muscle in patients with COPD [J].
Baraldo, S ;
Turato, G ;
Badin, C ;
Bazzan, E ;
Beghé, B ;
Zuin, R ;
Calabrese, F ;
Casoni, G ;
Maestrelli, P ;
Papi, A ;
Fabbri, LM ;
Saetta, M .
THORAX, 2004, 59 (04) :308-312
[9]
Corticosteroid resistance in chronic obstructive pulmonary disease: inactivation of histone deacetylase [J].
Barnes, PJ ;
Ito, K ;
Adcock, IM .
LANCET, 2004, 363 (9410) :731-733
[10]
Mouse models of rhinovirus-induced disease and exacerbation of allergic airway inflammation [J].
Bartlett, Nathan W. ;
Walton, Ross P. ;
Edwards, Michael R. ;
Aniscenko, Juliya ;
Caramori, Gaetano ;
Zhu, Jie ;
Glanville, Nicholas ;
Choy, Katherine J. ;
Jourdan, Patrick ;
Burnet, Jerome ;
Tuthill, Tobias J. ;
Pedrick, Michael S. ;
Hurle, Michael J. ;
Plumpton, Chris ;
Sharp, Nigel A. ;
Bussell, James N. ;
Swallow, Dallas M. ;
Schwarze, Jurgen ;
Guy, Bruno ;
WAlmond, Jeffrey ;
Jeffery, Peter K. ;
Lloyd, Clare M. ;
Papi, Alberto ;
Killington, Richard A. ;
Rowlands, David J. ;
Blair, Edward D. ;
Clarke, Neil J. ;
Johnston, Sebastian L. .
NATURE MEDICINE, 2008, 14 (02) :199-204