The resolution of inflammation: Anti-inflammatory roles for NF-κB

Inflammation is a salutary response to insult or injury that normally resolves with no detriment to host. While the mechanisms and mediators that regulate the onset of inflammation have been well characterized we still know relatively little about the endogenous mechanisms that terminate the inflammatory response (Lawrence and Gilroy, 2007). Nuclear factor (NF)-kappa B is a generic term for a family ubiquitous transcription factors with diverse physiological functions (Bonizzi and Karin, 2004: Caamano and Hunter, 2002). NF-kappa B transcription factors are formed by dimerisation of Rel proteins; RelA (p65), c-Rel, RelB, p50, p52. Various hetero or homodimers of Rel proteins can be formed in a tissue and stimulus specific manner, genetic evidence suggests these transcription factors have a critical role in cell survival and pro-inflammatory signalling pathways, which have been extensively reviewed elsewhere (Bonizzi and Karin, 2004; Caamano and Hunter, 2002). The critical role for NF-kappa B in pro-inflammatory gene expression has led to an enormous effort to develop inhibitors of this pathway for the of chronic inflammation (Karin et al., 2004). However, recent research using modern molecular genetic approaches has revealed new anti-inflammatory roles for NF-kappa B that may have important implications for targeting this pathway in the treatment of inflammatory diseases. In this review we will discuss the emerging role of NF-kappa B in the resolution of inflammation and some of the potential mechanisms attributed to this function. (C) 2010 Elsevier Ltd. All rights reserved.