Genome-Wide Analysis of Gene Expression in T Cells to Identify Targets of the NF-κB Transcription Factor c-Rel

Bunting, Karen; Rao, Sudha; Hardy, Kristine; Woltring, Donna; Denyer, Gareth; Wang, Jun; Gerondakis, Steve; Shannon, M. Frances

doi:10.4049/jimmunol.178.11.7097

Cited by 105 publications

(97 citation statements)

References 58 publications

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“…It has been reported that activation of NF-kB and its dependent genes may be one of the important pathways used by IL-8 during inflammation angiogenesis [27]. c-Rel, a number of NFkB family and predominantly expressed in immune cells, could regulate gene transcription in T cells and was implicated in leukocyte trafficking, particularly that related to Th1-mediated inflammation [36]. Six binding sites for c-Rel located within turtle IL-8 gene promoter region suggests that c-Rel plays an important role in controlling turtle IL-8 gene transcription in inflammatory responses.…”

Section: Discussionmentioning

confidence: 99%

Molecular characterization and expression profiles in response to bacterial infection of Chinese soft-shelled turtle interleukin-8 (IL-8), the first reptilian chemokine gene

Zhou

Guo

Dai

2009

Developmental & Comparative Immunology

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Section: Discussionmentioning

confidence: 99%

Molecular characterization and expression profiles in response to bacterial infection of Chinese soft-shelled turtle interleukin-8 (IL-8), the first reptilian chemokine gene

Zhou

Guo

Dai

2009

Developmental & Comparative Immunology

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“…To investigate the detailed mechanism involved in the repression of PP2Aca and PP2Acb transcription, we analyzed the potential binding sites of NF-kB or NF-kB downstream genes [28][29][30] in the 5 0 upstream regions of PP2Aca and PP2Acb by using Genomatix software. 31 In addition to NFkB itself, the potential binding sites of several transcription factors, which have been proven to be the target genes of the NF-kB pathway, were identified ( Figure 5G).…”

Section: Inflammatory Stimuli Repressed Pp2ac Expression In An Nf-kbmentioning

confidence: 99%

Inflammatory stimuli promote growth and invasion of pancreatic cancer cells through NF-κB pathway dependent repression of PP2Ac

et al. 2016

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Previous studies have indicated that inflammatory stimulation represses protein phosphatase 2A (PP2A), a well-known tumor suppressor. However, whether PP2A repression participates in pancreatic cancer progression has not been verified. We used lipopolysaccharide (LPS) and macrophage-conditioned medium (MCM) to establish in vitro inflammation models, and investigated whether inflammatory stimuli affect pancreatic cancer cell growth and invasion PP2A catalytic subunit (PP2Ac)-dependently. Via nude mouse models of orthotopic tumor xenografts and dibutyltin dichloride (DBTC)-induced chronic pancreatitis, we evaluated the effect of an inflammatory microenvironment on PP2Ac expression in vivo. We cloned the PP2Aca and PP2Acb isoform promoters to investigate the PP2Ac transcriptional regulation mechanisms. MCM accelerated pancreatic cancer cell growth; MCM and LPS promoted cell invasion. DBTC promoted xenograft growth and metastasis, induced tumor-associated macrophage infiltration, promoted angiogenesis, activated the nuclear factor-kB (NF-kB) pathway, and repressed PP2Ac expression. In vitro, LPS and MCM downregulated PP2Ac mRNA and protein. PP2Aca overexpression attenuated JNK, ERK, PKC, and IKK phosphorylation, and impaired LPS/MCM-stimulated cell invasion and MCM-promoted cell growth. LPS and MCM activated the NF-kB pathway in vitro. LPS and MCM induced IKK and IkB phosphorylation, leading to p65/RelA nuclear translocation and transcriptional activation. Overexpression of the dominant negative forms of IKKa attenuated LPS and MCM downregulation of PP2Ac, suggesting inflammatory stimuli repress PP2Ac expression NF-kB pathway-dependently. Luciferase reporter gene assay verified that LPS and MCM downregulated PP2Ac transcription through an NF-kB-dependent pathway. Our study presents a new mechanism in inflammation-driven cancer progression through NF-kB pathway-dependent PP2Ac repression.

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“…The IkK signaling pathway is activated by extracellular cytokines (such as interleukin 1 beta (IL-1b) and IL-6), infectious agents, glutamate, and neurotrophins (Israel, 2010;O'Neill and Kaltschmidt, 1997;Schölzke et al, 2003). Downstream of IkK, many target genes of the NFkB transcriptional complex contribute significantly to synaptic plasticity, such as NCAM, BDNF, opioid receptors, glutamate receptors, and neuregulin (Bunting et al, 2007;Chen et al, 2006;Frensing et al, 2008;Richter et al, 2002;Saha et al, 2006). Indeed, c-Rel, a member of the NFkB transcriptional complex, is required for long-term potentiation in the hippocampus (Ahn et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Effects of Inhibitor of κB Kinase Activity in the Nucleus Accumbens on Emotional Behavior

Christoffel

Golden

Heshmati

et al. 2012

Neuropsychopharmacol

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Inhibitor of kB kinase (IkK) has historically been studied in the context of immune response and inflammation, but recent evidence demonstrates that IkK activity is necessary and sufficient for regulation of neuronal function. Chronic social defeat stress of mice increases IkK activity in the nucleus accumbens (NAc) and this increase is strongly correlated to depression-like behaviors. Inhibition of IkK signaling results in a reversal of chronic social defeat stress-induced social avoidance behavior. Here, we more completely define the role of IkK in anxiety and depressive-like behaviors. Mice underwent stereotaxic microinjection of a herpes simplex virus expressing either green fluorescent protein, a constitutively active form of IkK (IkKca), or a dominant negative form of IkK into the NAc. Of all three experimental groups, only mice expressing IkKca show a behavioral phenotype. Expression of IkKca results in a decrease in the time spent in the nonperiphery zones of an open field arena and increased time spent immobile during a forced swim test. No baseline differences in sucrose preference were observed, but following the acute swim stress we noted a marked reduction in sucrose preference. To determine whether IkK activity alters responses to other acute stressors, we examined behavior and spine morphology in mice undergoing an acute social defeat stress. We found that IkKca enhanced social avoidance behavior and promoted thin spine formation. These data show that IkK in NAc is a critical regulator of both depressive-and anxiety-like states and may do so by promoting the formation of immature excitatory synapses.

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Genome-Wide Analysis of Gene Expression in T Cells to Identify Targets of the NF-κB Transcription Factor c-Rel

Cited by 105 publications

References 58 publications

Molecular characterization and expression profiles in response to bacterial infection of Chinese soft-shelled turtle interleukin-8 (IL-8), the first reptilian chemokine gene

Molecular characterization and expression profiles in response to bacterial infection of Chinese soft-shelled turtle interleukin-8 (IL-8), the first reptilian chemokine gene

Inflammatory stimuli promote growth and invasion of pancreatic cancer cells through NF-κB pathway dependent repression of PP2Ac

Effects of Inhibitor of κB Kinase Activity in the Nucleus Accumbens on Emotional Behavior

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