Transcription factor-κB (NF-κB) and renal disease

Abstract

Transcription factor-kappa B (NF-kappa B) and renal disease. Nuclear factor-kappa B (NF-kappa B) comprises a family of dimeric transcription factors that regulate the expression of numerous genes involved in inflammation and cell proliferation. Although NF-kappa B was initially identified in lymphocytes, it has been found to be a transcription factor present in virtually all cell types. In resting cells, NF-kappa B dimers remain in the cytoplasm in an inactive form bound to the inhibitory subunit I kappa B. Upon stimulation, I kappa B is phosphorylated, ubiquitinylated, and ultimately degraded by proteolytic cleavage by the proteasome system. As a result, NF-kappa B dimers are translocated into the nucleus and activate the transcription of target genes. Increasing data suggest a pivotal role for NF-kappa B in a variety of pathophysiological conditions in which either inflammation or cell number control are critical events. NF-kappa B has been found to be activated in experimental renal disease. Importantly, both in vivo and in vitro, NF-kappa B activation can be modulated by pharmacological maneuvers. Indeed, it is now widely acknowledged that the anti-inflammatory action of steroids is basically obtained through the inhibition of the transactivation of NF-kappa B-dependent genes. In addition, some of the beneficial effects of angiotensin-converting enzyme inhibitors and statins may, at least in part, be mediated by an inhibition of NF-kappa B activation. A better understanding of the mechanisms involved in NF-kappa B regulation and its modulation may provide new tools to improve the treatment of renal diseases with a better sound pathophysiological approach.

Activation of the Signal Transducer and Activator of Transcription Signaling Pathway in Renal Proximal Tubular Cells by Albumin

“…This is a previously reported result that supports our finding that serum deprivation can induce elevated ROS and an oxidative state in cells (48). Nuclear factor kappa B (NF-B) is also induced by ROS (38) and is one of the key components that cause immune reactions in kidneys (49). A recent report of a new and interesting Stat5 signal transduction mechanism suggests that Stat5 could be a potential activator of NF-〉 in some types of hematopoietic cells (50).…”

Diabetic nephropathy is associated with low-grade inflammation in Type 1 diabetic patients

“…The patients with microalbuminuria or macroalbuminuria, in contrast, were required to be treated with an ACE-inhibitor to be representative of Type 1 diabetic patients with increased AER in our country. Since these drugs are suggested to reduce the concentrations of CRP and IL-6 [20,21], ACE-inhibition could actually have diminished the true differences in inflammatory markers between the patient groups. This further underlines that diabetic nephropathy is a state of low-grade inflammation.…”

“…Interestingly, statins and ACE-inhibitors inhibit mesangial cell nuclear factor-κB activation and expression of pro-inflammatory cytokines such as IL-6, which suggests that some of the beneficial effects of statins and ACE-inhibitors could at least in part be mediated via pro-inflammatory genes [21].…”

High intensity interval training favourably affects antioxidant and inflammation mRNA expression in early-stage chronic kidney disease

“…Inflammatory cytokines such as tumour necrosis factor-α (TNFα) activate signalling pathways that promote nuclear factor κB (NFκB) transcription factors by binding to TNFα receptors, such as tumour necrosis factor receptor superfamily, member 1b (TNFRSF1b) [9].…”

“…NFκB transcription factors prompt transcription of genes involved in systemic inflammatory responses, encouraging generation of radicals via phagocytic activity [9]. Regulating NFκB-mediated INF is one beneficial effect of endogenous antioxidant enzymes (eAO).…”