The NF-kappa B1 is a key regulator of acute but not chronic renal injury

作者：Fearn Amy; Situmorang Gerhard R; Fox Christopher; Oakley Fiona; Howarth Rachel; Wilson Caroline L; Kiosia Agklinta; Robson Michael G; Mann Derek A; Moles Anna; Sheerin Neil S^*

来源：Cell Death & Disease, 2017, 8(6): e2883.

DOI：10.1038/cddis.2017.233

The NF-kappa B 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-kappa B family can suppress the inflammatory response. NF-kappa B1, from the locus nf kappa b1, can inhibit transcription, acting as a brake to the recognised pro-inflammatory activity of other NF-kappa B subunits. We tested the function of NF-kappa B1 in an acute (nephrotoxic serum (NTS) nephritis) and a chronic (unilateral ureteric obstruction (UUO)) model of renal injury using NF-kappa B1 (nf kappa b1(-/-)) knockout mice. Deficiency in NF-kappa B1 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-kappa B1 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 nf kappa b1(-/-)mice but by day 10, disease severity was equivalent in wild type and nf kappa b1(-/-)mice. In conclusion, NF-kappa B1 modifies acute inflammatory renal injury but does not influence chronic fibrotic injury.

• 出版日期2017-6