Phosphorylation of NF-κB and IκB proteins: implications in cancer and inflammation

Viatour, Patrick; Merville, Marie‐Paule; Bours, Vincent; Chariot, Alain

doi:10.1016/j.tibs.2004.11.009

Cited by 1,335 publications

(1,169 citation statements)

References 86 publications

(108 reference statements)

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“…morphine injections, and the activated NF-κB co-localized with spinal neurons and astrocytes. The NF-κB activation was refl ected by the increased expression of p-p65, as NF-κB p65 requires phosphorylation prior to its binding to a specific target gene in the nucleus [38,39] . To further investigate the effects of NF-κB activation on the development and maintenance of morphine analgesic tolerance, we examined the effects of pre-and post-administration of PDTC or SN50, potent inhibitors of NF-κB with different mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Toll-like receptor 4-mediated nuclear factor-κB activation in spinal cord contributes to chronic morphine-induced analgesic tolerance and hyperalgesia in rats

et al. 2014

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Nuclear factor kappa B (NF-κB) in the spinal cord is involved in pro-infl ammatory cytokine-mediated pain facilitation. However, the role of NF-κB activation in chronic morphine-induced analgesic tolerance and the underlying mechanisms remain unclear. In the present study, we found that the level of phosphorylated NF-κB p65 (p-p65) was increased in the dorsal horn of the lumbar 4-6 segments after intrathecal administration of morphine for 7 consecutive days, and the p-p65 was co-localized with neurons and astrocytes. The expression of TNF-α and IL-1β was also increased in the same area. In addition, pretreatment with pyrrolidinedithiocarbamate (PDTC) or SN50, inhibitors of NF-κB, prevented the development of morphine analgesic tolerance and alleviated morphine withdrawal-induced allodynia and hyperalgesia. The increase in TNF-α and IL-1β expression induced by chronic morphine exposure was also partially blocked by PDTC pretreatment. In another experiment, rats receiving PDTC or SN50 beginning on day 7 of morphine injection showed partial recovery of the anti-nociceptive effects of morphine and attenuation of the withdrawal-induced abnormal pain. Meanwhile, intrathecal pretreatment with lipopolysaccharide from Rhodobacter sphae roides, an antagonist of toll-like receptor 4 (TLR4), blocked the activation of NF-κB, and prevented the development of morphine tolerance and withdrawalinduced abnormal pain. These data indicated that TLR4-mediated NF-κB activation in the spinal cord is involved in the development and maintenance of morphine analgesic tolerance and withdrawalinduced pain hypersensitivity.

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Section: Discussionmentioning

confidence: 99%

Toll-like receptor 4-mediated nuclear factor-κB activation in spinal cord contributes to chronic morphine-induced analgesic tolerance and hyperalgesia in rats

et al. 2014

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“…In resting cells, NF-κB is localized to the cytoplasm and binds to an inhibitor protein known as IκB (Viatour et al, 2005;Ghosh and Hayden, 2008). Extracellular stimuli such as viral or bacterial factors, oxidative stress, and pro-inflammatory cytokines such as IL-1 and TNF-α can trigger NF-κB-activated pathways, which in turn causes phosphorylation and subsequent proteasome-mediated degradation of the inhibitor of NF-κB proteins (IκB).…”

Section: Introductionmentioning

confidence: 99%

Aloe-emodin from rhubarb (Rheum rhabarbarum) inhibits lipopolysaccharide-induced inflammatory responses in RAW264.7 macrophages

Zhang

Meng

et al. 2014

Journal of Ethnopharmacology

163

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“…TNF-a has been proposed as a mediator with a variety of biological effects that include proinflammatory and immuno-regulatory properties [5][6][7]. Serum TNF-a and TNF-a mRNA levels, both in the liver and peripheral mononuclear cells, were found to be elevated in chronic hepatitis C patients [43], patients with alcoholic liver cirrhosis [44], and in rats with acute liver damage induced by carbon tetrachloride [45].…”

Section: Discussionmentioning

confidence: 99%

“…TNF-a is a potent inducer of NFjB, a key transcription factor that induces genes involved in inflammation, responses to infection, and stress. Activated HSCs predominantly express the classic NFjB p65:p50 complex [5][6][7]. Once activated, NFjB dimers are translocated to the nucleus wherein they stimulate the transcription of genes that carry NFjB binding motifs, including genes encoding iNOS and intercellular adhesion molecule-1 (ICAM-1) [46].…”

Section: Discussionmentioning

confidence: 99%

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Anti-Fibrotic Effects of Thalidomide on Hepatic Stellate Cells and Dimethylnitrosamine-Intoxicated Rats

Chong¹,

Hsu²,

Chiu

et al. 2006

J Biomed Sci

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SummaryTumor necrosis factor-alpha (TNF-a) plays a central role in cellular necrosis, apoptosis, organ failure, tissue damage, inflammation and fibrosis. These processes, occurring in liver injury, may lead to cirrhosis. Thalidomide, a-N-phthalidoglutarimide, (C 13 H 10 N 2 ) 4 , has been shown to have immunomodulatory and anti-inflammatory properties, possibly mediated through its anti-TNF-a effect. In this study, we investigated the in vitro and in vivo effects of thalidomide on hepatic fibrosis. A cell line of rat hepatic stellate cells (HSC-T6) was stimulated with transforming growth factor-b1 (TGF-b1) or TNF-a. The inhibitory effects of thalidomide on the NFjB signaling cascade and fibrosis markers including a-smooth muscle actin (a-SMA) and collagen, were assessed. An in vivo therapeutic study was conducted in dimethylnitrosamine (DMN)-treated rats, which were randomly assigned to 1 of 4 groups: vehicle (0.7% carboxyl methyl cellulose, CMC), thalidomide (40 mg/kg), thalidomide (200 mg/kg), or silymarin (50 mg/kg), each given by gavage twice daily for 3 weeks starting after 1 week of DMN administration. Thalidomide (100-800 nM) concentration-dependently inhibited NFjB transcriptional activity induced by TNF-a, including IKKa expression and IjBa phosphorylation in HSC-T6 cells. In addition, thalidomide also suppressed TGF-b1-induced a-SMA expression and collagen deposition in HSC-T6 cells. Fibrosis scores of livers from DMNtreated rats receiving high dose of thalidomide (0.89±0.20) were significantly reduced in comparison with those of DMN-treated rats receiving vehicle (1.56±0.18). Hepatic collagen contents of DMN rats were also significantly reduced by either thalidomide or silymarin treatment. Immunohistochemical double staining results showed that a-SMA-and NFjB-positive cells were decreased in the livers from DMN rats receiving either thalidomide or silymarin treatment. In addition, real-time PCR analysis indicated that hepatic mRNA expressions of TGF-b1, a-SMA, collagen 1a2, TNF-a and iNOS genes were attenuated by thalidomide treatment. In conclusion, our results showed that thalidomide inhibited activation of HSC-T6 cells by TNF-a and ameliorated liver fibrosis in DMN-intoxicated rats.

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Phosphorylation of NF-κB and IκB proteins: implications in cancer and inflammation

Cited by 1,335 publications

References 86 publications

Toll-like receptor 4-mediated nuclear factor-κB activation in spinal cord contributes to chronic morphine-induced analgesic tolerance and hyperalgesia in rats

Toll-like receptor 4-mediated nuclear factor-κB activation in spinal cord contributes to chronic morphine-induced analgesic tolerance and hyperalgesia in rats

Aloe-emodin from rhubarb (Rheum rhabarbarum) inhibits lipopolysaccharide-induced inflammatory responses in RAW264.7 macrophages

Anti-Fibrotic Effects of Thalidomide on Hepatic Stellate Cells and Dimethylnitrosamine-Intoxicated Rats

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