Nuclear factor kB NFkB

Recently, it has been shown that oxidant stress can induce the expression and replication of human immunodeficiency virus-1 (HIV-1) in a human T cell line [64], The effect was shown to be mediated by the transcription factor NFk,B, which was potently and rapidly activated by exposure of target cells to H2O2. Moreover, the activation of NFkB by a variety of stimuli including phorbol-12-myristate-13-acetate (PMA), calcium ionophores and tumour necrosis factor alpha (TNFa) was inhibited by the ROI scavenger, N-acetyl cysteine [64]. It was therefore suggested that the formation of ROI was the common mechanism involved in the activation of NFk,B by a variety of agents. 

The c-fos and c-jun products are contained in the API (Activator Protein 1) transcription factor. Recently, it was shown that this transcription factor is the target for the induction of anergy (tolerance) in T cells [68], Interestingly, although anergic T cells produce only low levels of IL-2, the levels of NFkB in anergic T cells are similar to those in activated cells. 

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Simon, M. M. et al., UVB light induces a nuclear factor kB (NFkB) activity independently from chromosomal DNA damage in cell-free cytosolic extracts, J. Invest. Dermatol. 102, 422 127, 1994. 

Nanoparticles in lungs at critical dose levels can initiate the oxidative stress-responsive transcription factors, such as nuclear factor kB (NFkB) and activator protein-1, and then translate the oxidative stress to release proinflammatory proteins such as IL6 and IL8 (64). This may lead to chronic degenerative pulmonary and cardiovascular disease. It is possible but not as yet proven that surface factors may trigger oxidative stress (64). 

An important compound with biological activity of clavines is represented by 6 as end product of EA biosynthesis in A. fumigatus. In animal experiments using rats, 6 exhibited vasorelaxant effects on isolated thoracic aortic rings independent of endothelial mediators. Several mechanisms are proposed for the vasorelaxant effect of 6. These results indicate that 6 has potential capacity in vascular protection and may be used as therapeutic dmg against cardiovascular diseases [78]. Treatment of mice with induced liver damage and colitis with 6 showed clear beneficial effects on these diseases [79, 80]. In addition, it has also been demonstrated that 6 exhibits potential relevance as an antiatherosclerotic agent. Inflammation processes like activation of toll-like receptor 4 (TLR 4) and nuclear factor kB (NFkB) have been shown to be responsible in the development... 

Olive oil has an effect on inflammation—olive oil decreases expression of VCAM-1 and interferes with activation of nuclear factor kB (NFkB) (96). 

MHC to exit the endoplasmic reticulum (ER). As a result, there is an endoplasmic reticulum stress response, which leads to activation of the transcription factor nuclear factor kB (NFkB) and further cytokine release with subsequent accumulation of misfoided MHC glycoproteins, including phosphorylated tau and amyloid-related proteins. (Reproduced fromDalakas [72].)... 

NFkB, nuclear factor kB BAPP, amyloid precursor protein ... 

NeuNac, A-acetylneuraminic acid (sialic),. /V-acetylneurarriirioside (sialoside), jV-acetylneuraminosyl acid (sialosyl) NEUT, neurotensin NEUT-R, neurotensin receptor NFkB, nuclear factor kB NEAT, nuclear factor of activated T cells NGF, nerve growth factor NGF-RTK, nerve growth factor receptor tyrosine kinase... 

Alternative substrates may exist for the PHDs proposed examples include RNA polymerase II and IkB kinase-P (which is negatively regulated by PHDl) (115, 116). However, unequivocal evidence (e.g., demonstration of hydroxylation by mass spectrometry) has not yet been demonstrated for these proteins. In contrast, FIH has been shown to catalyze hydroxylation of ankyrin repeat domain (ARD) proteins from the NFkB (nuclear factor kB) and Notch family at highly conserved as-paraginyl residues (117, 118). The ARD is a common protein motif, with over 200 human members of the ARD protein family being predicted. Evidence that ARD hydroxylation occurs frequently in human cells supports the assertion (117, 118) that posttranslational hydroxylation of cytoplasmic proteins in... 

Fig. 6.7 Interactions among exdtotoxidty, neuroinflammation, and oxidative stress following TBI. Plasma membrane (PM) Glutamate (Glu) phosphatidylcholine (PtdCho) cytosolic phospholipase A2 (CPLA2) lyso-phosphatidylchoUne (lyso-PtdCho) arachidonic acid (ARA) plateletactivating factor (PAF) secretory phospholipase A2 (SPLA2) reactive oxygen species (ROS) reactive nitrogen species (RNS) nitric oxide synthase (NOS) nuclear factor kB inhibited form (IkB/NFkB) nuclear factor KB-response element (NFkB-RE), inhibitory subunit of NFkB (IkB) tumor necrosis factor-a (TNF-a) interleukin-If (IL-lf ) interleukin-6 (IL-6) cyclooxygenase-2 (COX-2) lipoxygenase (LOX) peroxynitrite (ONOO ) inducible nitric oxide synthase (iNOS). Positive sign (+) indicates stimulation...

Fig. 3. Possible intracellular signaling cascade involved in regulation of cyclooxygenase (COX)-2 expression. Abbreviations AP-1, activator protein 1 ERK, extracellular signal-regulated protein kinase IkB, inhibitory Bk JNK, c-Jun NHj-terminal kinase MAPK, mitogen-activated protein kinase MKK, mitogen-activated protein kinase kinase NFkB, nuclear factor-KB NIK, NF-KB-inducing kinase PKC, protein kinase C TPA, 12-O-tetradecanoylphorbol-13-acetate ROS, reactive oxygen species UV, ultraviolet light.

Fig. 2. Proposed mechanism of vitamin E-mediated inhibition of prostaglandin (PG)E2 production. Abbreviations COX, cyclooxygenase NFkB, nuclear factor kB IkB, inhibitory kB erk, extracellular signal-regulated kinase JNK, c-Jun N-terminal kinase.

NFkB Inhibition of nuclear factor kappa B (NF-kB) activity... 

Two polysaccharides (TOP-1 and TOP-2) isolated from Taraxacum officinale exhibited anti-inflammatory activity by reducing expression of inducible oxide synthase (iNOS) and tumor necrosis factor (TNF)-a in LPS-stimulated RAW 264.7 cells. In cells treated with TOPs the inhibition of phosphorylation of inflammatory transcription factor, nuclear factor (NF)kB, and its upstream signaling molecule, PI3K/Akt, was observed. Then, TOPs exerted their anti-infammatory effect through the inhibition of NFkB expression [77]. In a previous paper the inhibitory effect of a polysaccharide from tomato wastes on NFkB expression was already described [78]. In particular, PS(1)... 

A major signalling pathway involves activation of a protein kinase that phosphorylates inhibitor kB proteins (IkBs) that normally inhibit the function of the nuclear transcription factor NFkB. Phosphorylation of IkB by the serine/threonine-specific IkB kinases (IKKs) leads to NFkB de-inhibition, nuclear translocation and expression of pro-inflammatory proteins such as inducible cyclooxygenase (iCOX) (which generates prostaglandins), inducible nitric oxide synthase (iNOS) (which generates vasodilatory and toxic free radicalgenerating NO) and pro-inflammatory cytokines. 

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