Sebban Hélène, Courtois Gilles
INSERM U697, Pavillon Bazin, Hôpital Saint-Louis, 1, Avenue Claude Vellefaux, 75010 Paris, France.
Biochem Pharmacol. 2006 Oct 30;72(9):1153-60. doi: 10.1016/j.bcp.2006.08.006. Epub 2006 Sep 11.
By responding to pro-inflammatory cytokines, such as IL-1beta and TNF-alpha, and controlling itself the expression of numerous mediators of inflammation, NF-kappaB plays a pivotal role in controlling the proper sequence of events characterizing the inflammation process. Although excessive NF-kappaB activation is often associated with inflammatory signs in many different tissues, impaired NF-kappaB activation can also generate inflammation. This is the case in humans suffering from the genetic disease incontinentia pigmenti that exhibit severe skin inflammation. Identifying the molecular basis of this pathology, mutations affecting the gene coding for NEMO, has allowed production of mouse models for investigating the disease. Their characterization supports the view that a very tight positive and negative regulation of the NF-kappaB signaling pathway is required in vivo to ensure not only a fine-tuned response to injury or infection but also to maintain tissue homeostasis.
通过对促炎细胞因子（如白细胞介素-1β和肿瘤坏死因子-α）作出反应，并自身控制众多炎症介质的表达，核因子-κB在控制表征炎症过程的一系列适当事件中发挥着关键作用。尽管在许多不同组织中，核因子-κB的过度激活通常与炎症体征相关，但核因子-κB激活受损也会引发炎症。患有色素失禁症这种遗传病的人类就出现了这种情况，他们表现出严重的皮肤炎症。通过鉴定这种病理学的分子基础，即影响编码NEMO的基因的突变，得以制备用于研究该疾病的小鼠模型。对这些模型的特征描述支持了这样一种观点，即体内需要对核因子-κB信号通路进行非常严格的正负调控，以确保不仅对损伤或感染做出微调反应，而且维持组织稳态。
