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

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.