Recent Advances in Understanding NF-κB Regulation

Boone, David L.; Lee, Eric G.; Libby, Shon; Gibson, P.; Chien, Marcia; Chan, Faye; Madonia, Michelle; Burkett, Patrick R.; Ma, Averil

doi:10.1097/00054725-200205000-00008

Cited by 46 publications

(41 citation statements)

References 131 publications

(191 reference statements)

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“…48,64 In fact, some biochemical evidence suggests that the inhibitory effects of A20 on this signaling might involve an action at the level of either TRAF2 or of another molecule positioned immediately downstream of TNF-R1 (Figure 3). 48,120,121,123 Accordingly, A20 appears to selectively hinder NF-kB and JNK activations induced by TNF-Rs, and to have no effect on these activations downstream of IL-1b receptor -shown by analyses of A20 À/À MEFs.…”

Section: A20mentioning

confidence: 92%

“…120,121 This is rapidly induced by TNFa through a mechanism that depends on NF-kB, 3,121 and this induction by NF-kB plays an essential role in downmodulation of JNK signaling activated downstream of TNF-Rs (Figure 3). 120,121 Accordingly, A20…”

Section: A20mentioning

confidence: 99%

“…120,121 Notably, however, overexpressed A20 is incapable of protecting NF-kB-deficient cells against TNFa-induced killing. 3,121 Hence, while being required, upregulation of A20 alone appears to be insufficient to account for the NF-kB-mediated suppression of TNFa-induced JNK signaling and PCD. The precise mechanism(s) by which A20 blunts activation of the JNK cascade are not known.…”

Section: A20mentioning

confidence: 99%

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The NF-κB-mediated control of the JNK cascade in the antagonism of programmed cell death in health and disease

et al. 2006

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NF-jB/Rel transcription factors have recently emerged as crucial regulators of cell survival. Activation of NF-jB antagonizes programmed cell death (PCD) induced by tumor necrosis factor-receptors (TNF-Rs) and several other triggers. This prosurvival activity of NF-jB participates in a wide range of biological processes, including immunity, lymphopoiesis and development. It is also crucial for pathogenesis of various cancers, chronic inflammation and certain hereditary disorders. This participation of NF-jB in survival signaling often involves an antagonism of PCD triggered by TNF-Rfamily receptors, and is mediated through a suppression of the formation of reactive oxygen species (ROS) and a control of sustained activation of the Jun-N-terminal kinase (JNK) cascade. Effectors of this antagonistic activity of NF-jB on this ROS/JNK pathway have been recently identified. Indeed, further delineating the mechanisms by which NF-jB promotes cell survival might hold the key to developing new highly effective therapies for treatment of widespread human diseases.

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Section: A20mentioning

confidence: 92%

Section: A20mentioning

confidence: 99%

Section: A20mentioning

confidence: 99%

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The NF-κB-mediated control of the JNK cascade in the antagonism of programmed cell death in health and disease

et al. 2006

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“…16,20 Inflammatory mediators, including tumor necrosis factor alpha (TNFa), interleukin-1 (IL-1), and IL-6 have been demonstrated in blister 23 and spinal cord fluid1 of CRPS patients, and can activate or are activated themselves by NFkB. 9,26,48 Moreover, NFkB interacts with neuropeptides such as calcitonin gene related protein (CGRP) 35 and substance P (SP) 36 that have been found abnormally expressed during CRPS. 7,34 Finally, animal studies have revealed that NFkB is involved in spinal plasticity 39 and the development of neuropathic pain.…”

Section: Introductionmentioning

confidence: 99%

Role of NFκB in an Animal Model of Complex Regional Pain Syndrome–type I (CRPS-I)

Mos¹,

Laferrière

Millecamps

et al. 2009

The Journal of Pain

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NFκB is involved in several pathogenic mechanisms that are believed to underlie the complex regional pain syndrome (CRPS), including ischemia, inflammation and sensitization. Chronic post-ischemia pain (CPIP) has been developed as an animal model that mimics the symptoms of CRPS-I. The possible involvement of NFκB in CRPS-I was studied in CPIP rats. Under sodium pentobarbital anesthesia a tourniquet was placed around the rat left ankle joint, producing 3 h ours of ischemia, followed by rapid reperfusion (IR Injury). NFκB was measured in nuclear extracts of muscle and spinal cord tissue using ELISA. Moreover, the anti-allodynic (mechanical and cold) effect was tested for systemic, intrathecal, or intraplantar treatment with the NFkB inhibitor pyrrolidine dithiocarbamate (PDTC). At 2 and 48 hrs after IR injury, NFκB was elevated in muscle and spinal cord of CPIP rats compared to sham rats. At 7 days, NFκB levels were normalized in muscle, but were still elevated in spinal cord tissue. Systemic PDTC treatment relieved mechanical and cold allodynia in a dose-dependent manner, lasting for at least three hours. Intrathecal --but not intraplantar --administration also relieved mechanical allodynia. The results suggest that muscle and spinal NFκB plays a role in the pathogenesis of CPIP and potentially of human CRPS.

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“…A number of different NF-jB proteins are known (for a review see [7][8][9]), and the ones most likely to be activated by TLR4 are heterodimers of p65/RelA and p50 [10] held in the cytoplasm in an inactive form by the inhibitory protein I-jB [11]. Upon stimulation by LPS, the TLR4/MD2 complex relays signals that effectuate phosphorylation and ubiquitin-mediated degradation of I-jBa (reviewed in [11]), allowing for phosphorylation of p65 and entry of p65/p50 heterodimers into the nucleus, where they bind to cognate target gene promoters (reviewed in [11][12][13]).…”

Section: Introductionmentioning

confidence: 99%

The zinc finger protein Gfi1 acts upstream of TNF to attenuate endotoxin‐mediated inflammatory responses in the lung

et al. 2006

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Gfi1 is a 55-kD nuclear zinc finger protein that is differentially expressed in lymphoid and myeloid cells. Gfi1 -/-mice show a very strong systemic response to the endotoxin LPS and die rapidly within 36 h with symptoms of septic shock. Here we report that the pathohysiological processes for this exaggerated inflammatory response take place in the lung. After LPS treatment, lungs of Gfi1 -/-mice showed a rapid accumulation of mononuclear cells and a significant overproduction of inflammatory cytokines such as TNF, IL-1b and IL-6. Increased cytokine production was also observed in blood-free perfused lungs from Gfi1 -/-mice exposed to either LPS or overventilation. Alveolar macrophages but not airway epithelial cells from Gfi1 -/-mice were found to be responsible for the enhanced cytokine production. Strikingly, when the TNF gene was deleted, Gfi1 -/-animals were completely rescued from LPS hypersensitivity and had significantly lower IL-1b and IL-6 levels. We conclude that the unrestrained endotoxin response of Gfi1 -/-mice occurs mainly in the lung and that Gfi1 represents a novel factor limiting the inflammatory immune response of this organ, and propose that Gfi1 exerts its regulatory function in alveolar macrophages downstream of the LPS receptor (TLR4) and upstream of TNF.

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Recent Advances in Understanding NF-κB Regulation

Cited by 46 publications

References 131 publications

The NF-κB-mediated control of the JNK cascade in the antagonism of programmed cell death in health and disease

The NF-κB-mediated control of the JNK cascade in the antagonism of programmed cell death in health and disease

Role of NFκB in an Animal Model of Complex Regional Pain Syndrome–type I (CRPS-I)

The zinc finger protein Gfi1 acts upstream of TNF to attenuate endotoxin‐mediated inflammatory responses in the lung

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