The resolution of inflammation: anti-inflammatory roles for NF-kappaB.
Inflammation is a salutary response to insult or injury that normally resolves with no detriment to the 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)-kappaB is a generic term for a family of ubiquitous transcription factors with diverse physiological functions (Bonizzi and Karin, 2004; Caamano and Hunter, 2002). NF-kappaB 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-kappaB in pro-inflammatory gene expression has led to an enormous effort to develop inhibitors of this pathway for the treatment of chronic inflammation (Karin et al., 2004). However, recent research using modern molecular genetic approaches has revealed new anti-inflammatory roles for NF-kappaB 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-kappaB in the resolution of inflammation and some of the potential mechanisms attributed to this function.
Lawrence
Toby
T
Inflammation Biology Group, Centre d'Immunologie Marseille Luminy, CNRS-INSERM-Université de la Mediterranée, Parc Scientifique de Luminy, 13288 Marseille, France. lawrence@ciml.univ-mrs.fr <lawrence@ciml.univ-mrs.fr>
Fong
Carol
C
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000276:immunology* / Q000378:metabolism; D017209:Apoptosis / Q000276:immunology; D019281:Dimerization; D006801:Humans; D007249:Inflammation; D008262:Macrophage Activation; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014945:Wound Healing
D000893:Anti-Inflammatory Agents; D016328:NF-kappa B