NOTE: NF-kB is a cellular transcription factor that has been reported to both inhibit and to activate apoptosis (controled cell killing). In cancer cells it is known for inhibition of apoptosis. Cell signals that activate it cause proliferation and cancer growth. It is held inactive by the inhibitor of kappa beta (IkB), while IkB kinase (IKKb) phosporylates the inhibitor, releasing and activating NF-kB.
Nuclear factor kB is activated by arachidonic acid but not by eicosapentaenoic acid.
Author information
The omega-6 arachidonic acid supplementation of the human promonocytic cell line U937 strongly stimulates the nuclear translocation of the transcription factor NF-kB. Inhibitors of arachidonate oxidative metabolism prevent NF-kB activation, indirectly indicating a role for prostaglandin and leukotriene metabolites in the genesis of this phenomenon. Of note, omega-3 eicosapentaenoic acid does not exert any effect on NF-kB DNA binding. In subsequent experiments, prostaglandin E2 consistently showed the ability to activate NF-kB in U937 promonocytic cells, as well as in J774 macrophages. NF-kB activation by arachidonate, together with the lack of effect by eicosapentaenoic acid, suggests a way to modulate the expression of certain genes by means of a suitable dietary n-6/n-3 fatty acid ratio.
Bcl10 is a positive regulator of antigen receptor-induced activation of NF-kappaB and neural tube closure.
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BcL10, a caspase recruitment domain (CARD)-containing protein identified from the t(1;14)(p22;q32) breakpoint in mucosa-associated lymphoid tissue (MALT) lymphomas, has been shown to induce apoptosis and activate NF-kappaB in vitro. We show that one-third of bcl10-/- embryos developed exencephaly, leading to embryonic lethality. Surprisingly, bcl10-/- cells retained susceptibility to various apoptotic stimuli in vivo and in vitro. However, surviving bcl10-/- mice were severely immunodeficient and bcl10-/- lymphocytes are defective in antigen receptor or PMA/Ionomycin-induced activation. Early tyrosine phosphorylation, MAPK and AP-1 activation, and Ca2+ signaling were normal in mutant lymphocytes, but antigen receptor-induced NF-kappaB activation was absent. Thus, Bcl10 functions as a positive regulator of lymphocyte proliferation that specifically connects antigen receptor signaling in B and T cells to NF-kappaB activation.
And of course cell proliferation promotes growth of carcinoma cells.
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Bcl10 Links Saturated Fat Overnutrition with Hepatocellular NF-κB Activation and Insulin Resistance
Summary
Genes
Nutr. 2009 Sep; 4(3): 215–222.
Published online 2009 Aug 26. doi: 10.1007/s12263-009-0133-6
PMCID: PMC2745749
Diet-induced obesity increases NF-kB signaling in reporter mice
Harald Carlsen,corresponding
author1 Fred Haugen,1 Susanne Zadelaar,2 Robert Kleemann,2 Teake Kooistra,2 Christian A. Drevon,1 and Rune Blomhoff1
Abstract
The nuclear factor (NF)-kB is a primary regulator of inflammatory responses and may be linked to pathology associated with obesity. We investigated the progression of NF-kB activity during a 12-week feeding period on a high-fat diet (HFD) or a low-fat diet (LFD) using NF-?B luciferase reporter mice. In vivo imaging of luciferase activity showed that NF-kB activity was higher in the HFD mice compared with LFD-fed mice. Thorax region of HFD females displayed fourfold higher activity compared with LFD females, while no such increase was evident in males. In male HFD mice, abdominal NF-kB activity was increased twofold compared with the LFD males, while females had unchanged NF-kB activity in the abdomen by HFD. HFD males, but not females, exhibited evident glucose intolerance during the study.
In conclusion, HFD increased NF-kB activity in both female and male mice. However, HFD differentially increased activity in males and females. The moderate increase in abdomen of male mice may be linked to glucose intolerance.
Diabetes
2015;64:2015–2027 | DOI: 10.2337/db14-0093
Central Inhibition of IKKb/NF-kB Signaling Attenuates High-Fat Diet–Induced Obesity and Glucose Intolerance
Jonas
Benzler,1 Goutham K. Ganjam,2 Dominik Pretz,1 Rebecca Oelkrug,1 Christiane E. Koch,1 Karen Legler,1 Sigrid Stöhr,1 Carsten Culmsee,2 Lynda M. Williams,3 and Alexander Tups1,4
ABSTRACT
Metabolic inflammation in the central
nervous system might be causative for the development of over nutrition induced metabolic syndrome and related disorders, such as obesity, leptin and insulin resistance, and type 2 diabetes. Here we investigated whether nutritive and genetic inhibition of
the central IkB kinase b (IKKb)/nuclear factor-kB (NF-kB) pathway in diet-induced obese (DIO) and leptin-deficient mice improves these metabolic impairments. A known prominent inhibitor of IKKb/NF-kB signaling is the dietary flavonoid butein. We initially
determined that oral, intraperitoneal, and intracerebroventricular administration of this flavonoid improved glucose tolerance and hypothalamic insulin signaling. The dosedependent glucose-lowering capacity was profound regardless of whether obesity was caused
by leptin deficiency or high-fat diet (HFD). To confirm the apparent
central role of IKKb/NF-kB signaling in the control of glucose and energy homeostasis, we genetically inhibited this pathway in neurons of the arcuate nucleus, one key center for
control of energy homeostasis, via specific adeno-associated virus serotype 2–mediated overexpression of IkBa, which inhibits NF-kB nuclear translocation. This treatment attenuated HFD-induced body weight gain, body fat mass accumulation, increased energy
expenditure, and reduced arcuate suppressor of cytokine signaling 3 expression, indicative for enhanced leptin signaling. These results reinforce a specific role of central proinflammatory IKKb/NF-kB signaling in the development and potential treatment of
DIO-induced comorbidities.