Targeting the NF-kappaB pathway in asthma and chronic obstructive pulmonary disease.
Targeting the NF-kappaB pathway in asthma and chronic obstructive pulmonary disease.
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DOI：
10.1016/j.pharmthera.2008.09.003
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发表时间：
2009-01
影响因子：
13.5
通讯作者：
Johnston SL
中科院分区：
文献类型：
--
作者：
Edwards MR;Bartlett NW;Clarke D;Birrell M;Belvisi M;Johnston SL
哮喘和慢性阻塞性肺疾病是炎症性肺部疾病，在全球范围内造成显著的发病率和死亡率。虽然过敏反应在哮喘中的重要性是众所周知的，但呼吸道病毒和细菌感染以及污染物特别是香烟烟雾是这两种疾病发病机制中的重要因素。皮质类固醇治疗仍然是这两种疾病的首选治疗方法，但这些治疗并不总是完全有效，并且与副作用和类固醇耐药性有关。由于这些限制，开发新的治疗方法是制药行业和学术研究人员的主要目标。现在有很好的理由促进NF-κB信号传导中间体和Rel家族蛋白作为哮喘和慢性阻塞性肺疾病的潜在治疗靶点。这一观点得到以下事实的支持：两种疾病的大部分潜在炎症不依赖于刺激，至少部分是由几种细胞类型中NF-κB介导的信号传导事件介导的。此外，现在可获得一系列NF-κB信号传导中间体的抑制剂，包括作为NF-κB诱饵序列的DNA寡核苷酸和DNA-肽分子、小分子抑制剂如IKK-β抑制剂和影响NF-κB信号传导的蛋白酶体抑制剂，这些抑制剂在动物模型中显示出前景或已开始在其他疾病中进行临床试验。本文将重点介绍NF-κB在这两种疾病中的作用，讨论其作为靶点的适用性，并强调最近支持NF-κB作为这两种重要炎症性肺病治疗靶点的关键研究。
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-κB 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-κB mediated signalling events in several cell types. Also, a range of inhibitors of NF-κB signalling intermediates are now available, including DNA oligonucleotides and DNA-peptide molecules that act as NF-κB decoy sequences, small molecule inhibitors such as IKK-β inhibitors, and proteasome inhibitors affecting NF-κB 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-κB in both diseases, will discuss its suitability as a target, and will highlight recent key studies that support the potential of NF-κB as a therapeutic target in these two important inflammatory lung diseases.
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DOI：
10.1164/ajrccm.160.6.9808146
发表时间：
1999-12-01
影响因子：
24.7
作者：
Borish, LC;Nelson, HS;Garrison, L
通讯作者：
Garrison, L
影响因子：
56.9
作者：
Brightbill, HD;Libraty, DH;Modlin, RL
通讯作者：
Modlin, RL
糖皮质激素受体激活蛋白1在类固醇哮喘中的相互作用。
影响因子：
15.3
作者：
Adcock, Ian M.;Lane, Stephen J.;Brown, Carolanne R.;Lee, Tak H.;Barnes, Peter J.
通讯作者：
Barnes, Peter J.
影响因子：
168.9
作者：
Calverley, P;Pauwels, R;Maden, C
通讯作者：
Maden, C
影响因子：
9.6
作者：
BALL, P
通讯作者：
BALL, P