Inhibitory action of novel aromatic diamine compound on lipopolysaccharide‐induced nuclear translocation of NF‐κB without affecting IκB degradation

Shin, Hyun-Mo; Kim, Min-Hee; Kim, Byung Hak; Jung, Sang‐Hun; Kim, Yeong Shik; Park, Hye Ji; Hong, Jin Tae; Min, Kyung Rak; Kim, Youngsoo

doi:10.1016/j.febslet.2004.06.056

Cited by 216 publications

(164 citation statements)

References 22 publications

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“…Activation of the hypothalamic-pituitary-adrenal axis and elevation of glucocorticoids are typically associated with antiinflammatory responses, including inhibition of NF-κB signaling, via inhibition of IKK and inhibition of NF-κB transcription (17,18). However, there are also reports that stress can increase the effects of NF-κB, including enhancement of inflammatory responses (13,14,27).…”

Section: Discussionmentioning

confidence: 97%

“…A requirement for NF-κB is shown using two different selective inhibitors, one that blocks IkB kinase (IKK) (SC) and the dissociation of IκB and NF-κB and one that directly inhibits NF-κB (JSH) (17,18). Moreover, the results show that the antineurogenic effects of acute stress result from inhibition of NSC proliferation (Fig.…”

Section: Discussionmentioning

confidence: 98%

“…1A). Two selective structurally different NF-κB inhibitors were tested: JSH-23 (JSH) and SC-514 (SC) (17,18). Immediately after immobilization, rats were administered BrdU, a thymidine analogue that is incorporated into dividing cells (2 h post-BrdU injection).…”

Section: Nf-κb Signaling Mediates the Suppression Of Hippocampalmentioning

confidence: 99%

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Nuclear factor-κB is a critical mediator of stress-impaired neurogenesis and depressive behavior

Koo

Russo

Ferguson

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

548

389

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Proinflammatory cytokines, such as IL-1β, have been implicated in the cellular and behavioral effects of stress and in mood disorders, although the downstream signaling pathways underlying these effects have not been determined. In the present study, we demonstrate a critical role for NF-κB signaling in the actions of IL-1β and stress. Stress inhibition of neurogenesis in the adult hippocampus, which has been implicated in the prodepressive effects of stress, is blocked by administration of an inhibitor of NF-κB. Further analysis reveals that stress activates NF-κB signaling and decreases proliferation of neural stem-like cells but not early neural progenitor cells in the adult hippocampus. We also find that depressive-like behaviors caused by exposure to chronic stress are mediated by NF-κB signaling. Together, these data identify NF-κB signaling as a critical mediator of the antineurogenic and behavioral actions of stress and suggest previously undescribed therapeutical targets for depression.M ood disorders represent a major health concern, affecting over 15% of the population in developed countries, resulting in enormous personal and economic costs and, in many cases, suicide (1, 2). Despite significant efforts, the neurobiological mechanisms underlying depression have not been characterized. Both genetic and environmental factors contribute to depression, and traumatic or repeated stress is known to precipitate or exacerbate mood disorders (3-5). In addition, proinflammatory cytokines, including IL-1β, IL-6, and TNF-α, that are induced by injury and infection as well as by psychological stress have been implicated in depressive behavior in rodent models and depressed patients (6-8).Exposure to stress and depression can result in atrophy of limbic brain regions that control emotion and mood, including inhibition of neurogenesis in the adult hippocampus (5, 9, 10). Inhibition of neurogenesis is observed with many different types of physical and psychological stressors, but the types of cells, neural stem-like cells (NSCs) or intermediate transient amplifying neural progenitor cells (ANPs), that are influenced have not been characterized (9, 11). A role for proinflammatory cytokines is supported by a recent report that IL-1β signaling is necessary and sufficient for the antineurogenic and behavioral effects of stress (6). One possible signaling cascade that could mediate the effects of IL-1β is NF-κB, which is activated by IL-1β and other cytokines both in peripheral immune cells and in the brain (8,12). Chronic stress enhances the activation of NF-κB in response to inflammatory stimuli (13,14), and social stress increases NF-κB signaling in healthy subjects and produces an exaggerated response in depressed patients (15,16).In the present study, we investigate the role of NF-κB in the cellular and behavioral responses to acute and chronic stress. The results demonstrate that the inhibition of neurogenesis by stress occurs via activation of NF-κB in NSCs and that stress-induced anhedonia, a core symptom of depr...

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 98%

See 1 more Smart Citation

Nuclear factor-κB is a critical mediator of stress-impaired neurogenesis and depressive behavior

Koo

Russo

Ferguson

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

548

389

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“…This effect was reversed by LY341495 or by the PtdIns-3-K inhibitor, LY294002 (Figures 3c and d). The specific NF-kB inhibitor, 4-methyl-N1-(3-phenyl-propyl)-benzene-1,2-diamine (JSH-23), 18 enabled temozolomide toxicity and occluded the permissive action of LY341495 in GSCs (Figure 3e). Similar effects were obtained with salicylic acid (Supplementary Figure 4), which also inhibits NF-kB.…”

Section: Mergementioning

confidence: 99%

Type-3 metabotropic glutamate receptors regulate chemoresistance in glioma stem cells, and their levels are inversely related to survival in patients with malignant gliomas

et al. 2012

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Drug treatment of malignant gliomas is limited by the intrinsic resistance of glioma stem cells (GSCs) to chemotherapy. GSCs isolated from human glioblastoma multiforme (GBM) expressed metabotropic glutamate receptors (mGlu3 receptors). The DNAalkylating agent, temozolomide, killed GSCs only if mGlu3 receptors were knocked down or pharmacologically inhibited. In contrast, mGlu3 receptor blockade did not affect the action of paclitaxel, etoposide, cis-platinum, and irinotecan. mGlu3 receptor blockade enabled temozolomide toxicity by inhibiting a phosphatidylinositol-3-kinase/nuclear factor-jB pathway that supports the expression of O 6 -methylguanine-DNA methyltransferase (MGMT), an enzyme that confers resistance against DNAalkylating agents. In mice implanted with GSCs into the brain, temozolomide combined with mGlu3 receptor blockade substantially reduced tumor growth. Finally, 87 patients with GBM undergoing surgery followed by adjuvant chemotherapy with temozolomide survived for longer time if tumor cells expressed low levels of mGlu3 receptors. In addition, the methylation state of the MGMT gene promoter in tumor extracts influenced survival only in those patients with low expression of mGlu3 receptors in the tumor. These data encourage the use of mGlu3 receptor antagonists as add-on drugs in the treatment of GBM, and suggest that the transcript of mGlu3 receptors should be measured in tumor specimens for a correct prediction of patients' survival in response to temozolomide treatment.

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“…To examine whether the expression of CrI B is indeed affected by the NF-B pathway, we studied the effect of NF-B-specific inhibitors on the up-regulation of CrI B. Injection of DMSO (vehicle) did not affect activation of CrI B during infection (Fig. 3E), whereas treatment with three unrelated NF-B-specific inhibitors, helenalin, MG-132, or NF-B activation inhibitor II (JSH-23) (20), prior to infection consistently suppressed the up-regulation of CrI B. This indicates a possible role of the NF-B pathway in the regulation of CrI B expression in vivo.…”

mentioning

confidence: 99%

Evidence for the ancient origin of the NF-κB/IκB cascade: Its archaic role in pathogen infection and immunity

Wang

Tan²,

Ho³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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The evolutionary conservation of the NF-B transcription factors, from Drosophila to humans, underscores its pivotal role in immune response. Unexpectedly, the canonical NF-B signaling pathway is not functional in the immune system of Caenorhabditis elegans. Therefore, the ancient origin of the NF-B signaling pathway is still unknown. Here, we report the discovery and characterization of a primitive and functional NF-B͞I B pathway in the immune defense of a ''living fossil,'' the horseshoe crab, Carcinoscorpius rotundicauda. The ancient NF-B͞I B homologues, CrNF B, CrRelish, and CrI B, share numerous signature motifs with their vertebrate orthologues. CrNF B recognizes both horseshoe crab and mammalian B response elements. CrI B interacts with CrNF B and inhibits its nuclear translocation and DNA-binding activity. The activation of the CrNF B is autoregulated by a feedback mechanism mediated by CrI B, the natural inhibitor of CrNF B. We further show that Gram-negative bacteria infection causes rapid degradation of CrI B and nuclear translocation of CrNF B. Infection also leads to an increase in the B-binding activity and up-regulation of immune-related gene expression, like inducible nitric oxide synthase and Factor C, an LPS-activated serine protease. Altogether, our study shows that, although absent in C. elegans, the NF-B͞I B signaling cascade remains well conserved from horseshoe crab to humans, playing an archaic but fundamental role in regulating the expression of critical immune defense molecules.conservation and coevolution ͉ horseshoe crab ͉ infection and immune response ͉ transcriptional control T he family of NF-B transcription factors plays an indispensable role in immunity, inflammation, apoptosis, development, and differentiation (1, 2). NF-B dimers are held in an inactive cytoplasmic complex with a family of inhibitory proteins, the I Bs. Degradation of I Bs permits nuclear translocation of NF-B, where they stimulate the transcription of various immune-related genes (1). In Drosophila melanogaster, NF-B homologues (Dorsal, Dif, and Relish) are responsible for regulating several biological roles, including humoral immunity and development (3, 4). These important and diverse functions make NF-B one of the best-studied transcriptional factors in biology (2). Unexpectedly, in Caenorhabditis elegans, the NF-B protein is absent, and similar functional homologues (Toll, Traf, Cactus) are not involved in innate immune response (5). This led to the suggestion that the p38 mitogen-activated protein kinase pathway, which mediates the immune response in C. elegans, is the ancestral signaling pathway of the common ancestor of nematodes, arthropods, and vertebrates, predating the evolution of the NF-B immune signaling pathway (6). Thus, the ancient origin of the NF-B signaling pathway is still a conundrum, and it remains unclear whether the similarities between Drosophila and the human NF-B pathway have resulted from convergent evolution or reflect common ancestral pathways. Therefore, additional information on ...

show abstract

Inhibitory action of novel aromatic diamine compound on lipopolysaccharide‐induced nuclear translocation of NF‐κB without affecting IκB degradation

Cited by 216 publications

References 22 publications

Nuclear factor-κB is a critical mediator of stress-impaired neurogenesis and depressive behavior

Nuclear factor-κB is a critical mediator of stress-impaired neurogenesis and depressive behavior

Type-3 metabotropic glutamate receptors regulate chemoresistance in glioma stem cells, and their levels are inversely related to survival in patients with malignant gliomas

Evidence for the ancient origin of the NF-κB/IκB cascade: Its archaic role in pathogen infection and immunity

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