NF-KB/Rel proteins

Finally, two recent studies by Vancurova et al. [91] added new insights to our current understanding of the NF-kB system in neutrophils. In one instance, they found that TNF induces NF-kB more potently in neutrophils from newborn individuals, relative to neutrophils from adult donors this correlates well with the elevated production of IL-8 and IL-ip reported in neonatal neutrophils [93, 94], These authors also showed that dexamethasone inhibits NF-kB induction by TNF in both newborn and adult neutrophils [91] we observed a similar effect of dexamethasone in neutrophils from adult donors (our unpubl. data). In a later study, the same group demonstrated that IkB-o is distributed in approximately equal amounts between the cytoplasm and the nucleus of neutrophils [76] - in stark contrast to most other cell types. Moreover, TNF stimulation led to the degradation of iKB-a in both cellular compartments, in addition to its known ability to promote the nuclear recruitment of NF-KB/Rel proteins [76]. This effect of TNF could be partially blocked by MG-132, aproteasome inhibitor that is known to inhibit NF-kB [95], as well as by the PKC8 inhibitor, rottlerin [76]. 

Nuclear factor kappa B (NF-kB) is the generic term for a family of dimeric eukaryotic transcription factors, composed of members of the Rel family of DNA-binding proteins including the mammalian proteins RelA (or p65), cRel, RelB, p50 and p52, and the Drosophila proteins Dorsal, Dif and Relish. These proteins bind with different affinities to a consensus DNA sequence motif (called the kB site) consisting of the sequence 5 -GGGRNNYYCC-3 in which R is a purine, Y is a pyrimidine, and N is any base. 

Ghosh S, May M, Kopp EB (1998) NF-kB and Rel proteins evolutionarily conserved mediators of immune responses. Annu Rev Immunol 16 225—260... 

The Rel homology domain (RHD) is an evolutionarily conserved domain found in some eukaryotic transcription factors, including NF-kB, the nuclear factors of activated T-cells (NFATs) and the drosophila proteins Dif and Relish. Some of these transcription factors form... 

Essential for induction ofthe/Z-5 gene in inflammatory reactions is the binding site for nuclear factor kappa B (NF-kB). NF-kB responds to cytokines, stress, free radicals, ultraviolet irradiation, and bacterial, viral, or even parasitic antigens [2]. NF-kB stands for a family of subunits, which form homo-, and heterodimers. All NF-kB proteins share a highly conserved DNA-binding/dimerization domain called the Rel homology domain (RHD) consisting of two (3-strand core domains... 

Treatment of hippocampal slices with kainate produces a time-dependent increase in NF-/< B levels in areas CA3 and CA1, but not dentate gyrus, compared with controls (Lubin et al., 2005). The kainate-mediated NF-kB complex that binds to DNA is composed of p65, p50, and c-Rel subunits. Pharmacological studies indicate that extracellular signal-regulated protein kinase (ERK) and Ptdlns-3K... 

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