Institute of Cellular Medicine, Newcastle University, Newcastle Upon Tyne, UK.
Urology Department, Cipto Mangunkusumo National Referral Hospital/Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
Cell Death Dis. 2017 Jun 15;8(6):e2883. doi: 10.1038/cddis.2017.233.
The NF-κB family of transcription factors is important for many cellular functions, in particular initiation and propagation of inflammatory and immune responses. However, recent data has suggested that different subunits of the NF-κB family can suppress the inflammatory response. NF-κB1, from the locus nfκb1, can inhibit transcription, acting as a brake to the recognised pro-inflammatory activity of other NF-κB subunits. We tested the function of NF-κB1 in an acute (nephrotoxic serum (NTS) nephritis) and a chronic (unilateral ureteric obstruction (UUO)) model of renal injury using NF-κB1 (nfκb1) knockout mice. Deficiency in NF-κB1 increased the severity of glomerular injury in NTS-induced nephritis and was associated with greater proteinuria and persistent pro-inflammatory gene expression. Induction of disease in bone marrow chimeric mice demonstrated that the absence of NF-κB1 in either bone marrow or glomerular cells increased the severity of injury. Early after UUO (day 3) there was more severe histological injury in the nfκb1 mice but by day 10, disease severity was equivalent in wild type and nfκb1 mice. In conclusion, NF-κB1 modifies acute inflammatory renal injury but does not influence chronic fibrotic injury.
NF-κB 转录因子家族对于许多细胞功能非常重要，特别是炎症和免疫反应的起始和传播。然而，最近的数据表明，NF-κB 家族的不同亚基可以抑制炎症反应。来自 nfκb1 基因座的 NF-κB1 可以抑制转录，作为对其他 NF-κB 亚基公认的促炎活性的制动。我们使用 NF-κB1 (nfκb1) 敲除小鼠在急性（肾毒性血清 (NTS) 肾炎）和慢性（单侧输尿管梗阻 (UUO)）肾损伤模型中测试了 NF-κB1 的功能。在 NTS 诱导的肾炎中，NF-κB1 的缺乏增加了肾小球损伤的严重程度，并与蛋白尿增加和持续的促炎基因表达有关。在骨髓嵌合小鼠中诱导疾病表明，骨髓或肾小球细胞中缺乏 NF-κB1 会增加损伤的严重程度。UUO 后早期（第 3 天），nfκb1 小鼠的组织学损伤更严重，但到第 10 天，野生型和 nfκb1 小鼠的疾病严重程度相当。总之，NF-κB1 修饰急性炎症性肾损伤，但不影响慢性纤维性损伤。
