NF-kappaB activation by reactive oxygen species: fifteen years later.
The transcription factor NF-kappaB plays a major role in coordinating innate and adaptative immunity, cellular proliferation, apoptosis and development. Since the discovery in 1991 that NF-kappaB may be activated by H(2)O(2), several laboratories have put a considerable effort into dissecting the molecular mechanisms underlying this activation. Whereas early studies revealed an atypical mechanism of activation, leading to IkappaBalpha Y42 phosphorylation independently of IkappaB kinase (IKK), recent findings suggest that H(2)O(2) activates NF-kappaB mainly through the classical IKK-dependent pathway. The molecular mechanisms leading to IKK activation are, however, cell-type specific and will be presented here. In this review, we also describe the effect of other ROS (HOCl and (1)O(2)) and reactive nitrogen species on NF-kappaB activation. Finally, we critically review the recent data highlighting the role of ROS in NF-kappaB activation by proinflammatory cytokines (TNF-alpha and IL-1beta) and lipopolysaccharide (LPS), two major components of innate immunity.
Gloire
Geoffrey
G
Center for Biomedical Integrated Genoproteomics (CBIG), Virology and Immunology Unit, University of Liège, 4000 Liège, Belgium.
Legrand-Poels
Sylvie
S
Piette
Jacques
J
D000818:Animals; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006997:Hypochlorous Acid / Q000494:pharmacology; D051550:I-kappa B Kinase / Q000378:metabolism; D053583:Interleukin-1beta / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress; D026361:Reactive Nitrogen Species / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000494:pharmacology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D016328:NF-kappa B; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D006997:Hypochlorous Acid; D006861:Hydrogen Peroxide; D051550:I-kappa B Kinase