NF-κB activation by reactive oxygen species:: Fifteen years later

The transcription factor NF-kappa B plays a major role in coordinating innate and adaptative immunity, cellular proliferation, apoptosis and development. Since the discovery in 1991 that NF-kappa B maybe 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 I kappa B alpha Y42 phosphorylation independently Of I kappa B kinase (IKK), recent findings suggest that H2O2 activates NF-kappa B 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 O-1(2)) and reactive nitrogen species on NF-kappa B activation. Finally, we critically review the recent data highlighting the role of ROS in NF-kappa B activation by proinflammatory cytokines (TNF-alpha and IL-1 beta) and lipopolysaccharide (LPS), two major components of innate immunity. (c) 2006 Elsevier Inc. All rights reserved.