Anti-inflammatory inhibitors of IkappaB kinase in asthma and COPD.
Nuclear factor-kappaB (NFkappaB) is an inducible transcription factor that plays a central role in the regulation of many immune and inflammatory responses. While NFkappaB is required for cell survival and immunity, abnormal expression and/or activation of NFkappaB leads to the development of many pathological states, especially those involved in chronic and acute inflammation. Many different signal transduction pathways, originating from a wide variety of cellular stresses and stimuli, converge on a single target; the NFkappaB/IkappaB complex and its activating kinase (inhibitor of kappaB kinase, IKK). Here, we review some of the major NFkappaB activating pathways, their role in the pathogenesis of asthma and chronic obstructive pulmonary disease (COPD), and their potential as targets in the treatment of asthma and COPD.
Caramori
Gaetano
G
Airways Disease Section, National Heart and Lung Institute, Imperal College London, Dovehouse Street, London SW3 6LY, UK.
Adcock
Ian M
IM
Ito
Kazuhiro
K
D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy*; D006575:Heterocyclic Compounds, 3-Ring / Q000627:therapeutic use; D006801:Humans; D051550:I-kappa B Kinase; D007093:Imidazoles / Q000627:therapeutic use; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D011725:Pyridines / Q000627:therapeutic use; D011810:Quinoxalines / Q000627:therapeutic use
C471109:4(2'-aminoethyl)amino-1,8-dimethylimidazo(1,2-a)quinoxaline; D000893:Anti-Inflammatory Agents; D006575:Heterocyclic Compounds, 3-Ring; D007093:Imidazoles; D016328:NF-kappa B; C456319:PS1145; D011725:Pyridines; D011810:Quinoxalines; D017346:Protein Serine-Threonine Kinases; C496559:CHUK protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human