Inflammation Biology Group, Centre d'Immunologie Marseille Luminy, CNRS-INSERM-Université de la Mediterranée, Parc Scientifique de Luminy, 13288 Marseille, France.
Int J Biochem Cell Biol. 2010 Apr;42(4):519-23. doi: 10.1016/j.biocel.2009.12.016. Epub 2009 Dec 22.
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.
炎症是对损伤或感染的有益反应，通常不会对宿主造成损害而自行消退。虽然调控炎症发生的机制和介质已得到很好的描述，但我们对终止炎症反应的内源性机制仍知之甚少（Lawrence 和 Gilroy，2007）。核因子（NF）-κB 是一类具有多种生理功能的普遍转录因子的统称（Bonizzi 和 Karin，2004；Caamano 和 Hunter，2002）。NF-κB 转录因子由 Rel 蛋白二聚体形成；RelA（p65）、c-Rel、RelB、p50、p52。在组织和刺激特异性方式中可以形成各种 Rel 蛋白的异源或同源二聚体，遗传证据表明这些转录因子在细胞存活和促炎信号通路中具有关键作用，这些作用已在其他地方进行了广泛的综述（Bonizzi 和 Karin，2004；Caamano 和 Hunter，2002）。NF-κB 在促炎基因表达中的关键作用促使人们投入大量精力开发该途径的抑制剂，以治疗慢性炎症（Karin 等人，2004）。然而，最近使用现代分子遗传方法的研究揭示了 NF-κB 在炎症消退中的新的抗炎作用，这可能对靶向该途径治疗炎症性疾病具有重要意义。在这篇综述中，我们将讨论 NF-κB 在炎症消退中的作用以及归因于该功能的一些潜在机制。
