Chemical biology of inflammatory cytokine signaling

Kataoka, Takao

doi:10.1038/ja.2009.98

Cited by 51 publications

(32 citation statements)

References 151 publications

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“…It is generally accepted that many intracellular signal pathways participate in the LPS-induced activation of macrophages and resultant production of pro-inflammatory cytokines/ mediators, and that nuclear factor NF -κB and mitogenactivated protein kinase MAPK pathways play key roles. NF-κB is one of the most ubiquitous transcription factors and coordinates the expression of pro-inflammatory enzymes and cytokines, making it a popular target for the development of potent inhibitors as novel anti-infl ammatory drugs [21][22][23][24] . Given the role of NF-κB in modulating the expression of infl ammatory mediators, it is possible that the inhibitory effects of D-limonene involve the inhibition of the NF-κB signalling pathway.…”

Section: Discussionmentioning

confidence: 99%

Limonene Suppresses Lipopolysaccharide-Induced Production of Nitric Oxide, Prostaglandin E2, and Pro-inflammatory Cytokines in RAW 264.7 Macrophages

2010

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Section: Discussionmentioning

confidence: 99%

Limonene Suppresses Lipopolysaccharide-Induced Production of Nitric Oxide, Prostaglandin E2, and Pro-inflammatory Cytokines in RAW 264.7 Macrophages

2010

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“…8,9) We previously reported that (11S)-2α-bromo-3-oxoeudesmano-12,6α-lactone (1), initially designated as santonin-related compound 2 (SRC2; Fig. 1), inhibited cell-surface intercellular adhesion molecule-1 (ICAM-1) expression induced by interleukin-1β (IL-1β) in human lung carcinoma A549 cells.…”

Section: )mentioning

confidence: 99%

“…3) Sesquiterpene lactones are found in many plants, and have been attracting increasing attention for drug development due to their various biological activities, including anti-cancer and anti-inflammatory activities. 8,9) We previously reported that (11S)-2α-bromo-3-oxoeudesmano-12,6α-lactone (1), initially designated as santonin-related compound 2 (SRC2; Fig. 1), inhibited cell-surface intercellular adhesion molecule-1 (ICAM-1) expression induced by interleukin-1β (IL-1β) in human lung carcinoma A549 cells.…”

Section: )mentioning

confidence: 99%

Eudesmane-Type Sesquiterpene Lactones Inhibit Nuclear Translocation of the Nuclear Factor κB Subunit RelB in Response to a Lymphotoxin β Stimulation

Quach

Kondo

Watanabe

et al. 2017

Biological & Pharmaceutical Bulletin

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The transcription factor nuclear factor κB (NF-κB) regulates various biological processes, including inflammatory responses. We previously reported that eudesmane-type sesquiterpene lactones inhibited multiple steps in the canonical NF-κB signaling pathway induced by tumor necrosis factor-α and interleukin-1α. In contrast, the biological activities of eudesmane-type sesquiterpene lactones on the non-canonical NF-κB signaling pathway remain unclear. In the present study, we found that (11S)-2α-bromo-3-oxoeudesmano-12,6α-lactone, designated santonin-related compound 2 (SRC2), inhibited NF-κB luciferase reporter activity induced by lymphotoxin β (LTβ) in human lung carcinoma A549 cells. Although SRC2 did not prevent the processing of the NF-κB subunit p100 induced by LTβ, it inhibited the nuclear translocation of RelB and p52 in response to the LTβ stimulation. In contrast to ( )-dehydroxymethylepoxyquinomicin, SRC2 inhibited the LTβ-induced nuclear translocation of the RelB (C144S) mutant in a manner similar to wild-type RelB. While eudesmane derivatives possessing an α-bromoketone moiety or α,β-unsaturated carbonyl moieties inhibited LTβ-induced NF-κB luciferase reporter activity, eudesmane derivatives possessing an α-bromoketone moiety exhibited stronger inhibitory activity on the LTβ-induced nuclear translocation of RelB than those possessing a single α-methylene-γ-lactone moiety. The results of the present study revealed that SRC2 inhibits the nuclear translocation of RelB in the non-canonical NF-κB signaling pathway induced by LTβ.Key words eudesmane; lymphotoxin β; nuclear factor κB; RelB; sesquiterpene lactone Nuclear factor κB (NF-κB) is a family of structurally-related eukaryotic transcription factors that regulate the expression of a number of important genes, including those related to cell proliferation, cell death, and inflammation.1) The NF-κB family consists of five subunits: RelA(p65), RelB, c-Rel, p105/p50, and p100/p52. 2)Various types of stimuli, including inflammatory cytokines, activate the canonical and non-canonical NF-κB signaling pathways.3) In the canonical NF-κB pathway, tumor necrosis factor (TNF) family members, such as TNF-α, induce the activation of the inhibitor of NF-κB (IκB) kinase β. 4) In the cytosol, IκB sequesters the NF-κB heterodimers RelA and p50 and prevents their nuclear translocation. 4) Upon phosphorylation, IκB undergoes ubiquitination and proteasomal degradation, leading to the liberation and nuclear translocation of the RelA and p50 heterodimers. 5) In contrast, the non-canonical NF-κB pathway is triggered by other TNF family members, such as lymphotoxin β (LTβ).6) The NF-κB subunits RelB and p100/p52 play essential roles in the non-canonical NF-κB pathway. 7) In unstimulated cells, p100 constitutively associates with RelB in the cytosol and inhibits its activity.7) Upon a stimulation with LTβ, IκB kinase α is primarily activated and then directly phosphorylates p100.3) Phosphorylated p100 is ubiquitinated and processed into p52 by proteasome, leading to the nuclear ...

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“…Thus, it seems likely that the cardenolide aglycones act as translation inhibitors in the TNF-α-induced gene expression, except for those capable of inducing the ectodomain shedding of TNF receptor 1 and thereby blocking the TNF-α-induced NF-κB signaling pathway (e.g., glutarimides and triene-ansamycins). 39,40) Na + /K + -ATPase pumps Na + out and K + in via hydrolysis of ATP and plays a critical role in the maintenance of the Na + gradient across the plasma membrane. 41) The transport of amino acids across the plasma membrane is mediated by a broad range of transporters, including those coupling the influx of amino acids with the transmembrane gradient of Na + .…”

Section: Discussionmentioning

confidence: 99%

Cardenolide Aglycones Inhibit Tumor Necrosis Factor α-Induced Expression of Intercellular Adhesion Molecule-1 at the Translation Step by Blocking Na+/K+-ATPase

et al. 2015

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Cardiac glycosides, which are inhibitors of Na /K -ATPase, are classified into cardenolides and bufadienolides. We have recently shown that two cardenolide glycosides, ouabain and odoroside A, inhibit Na / K -ATPase, thereby preventing nuclear factor κB-inducible protein expression by blocking Na -dependent amino acid transport. In this study, we investigated the mechanism of action of cardenolide aglycones in tumor necrosis factor α (TNF-α)-induced gene expression. Ouabagenin, digitoxigenin, and digoxigenin were found to inhibit the TNF-α-induced cell-surface expression of intercellular adhesion molecule-1 (ICAM-1) in human lung carcinoma A549 cells. Those cardenolide aglycones did not inhibit the TNF-α-induced expression of ICAM-1 mRNA, but strongly inhibited the TNF-α-induced expression of ICAM-1 as translation product. The inhibition of the TNF-α-induced ICAM-1 expression by ouabagenin, digitoxigenin, and digoxigenin was significantly reversed by the ectopic expression of ouabain-resistant rat Na /K -ATPase α1 isoform. Moreover, knockdown of Na /K -ATPase α1 isoform augmented the inhibition of the TNF-α-induced ICAM-1 expression by ouabagenin or ouabain. These results clearly indicate that cardenolide aglycones inhibit the TNF-α-induced ICAM-1 expression at the translation step by blocking Na /K -ATPase.

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Chemical biology of inflammatory cytokine signaling

Cited by 51 publications

References 151 publications

Limonene Suppresses Lipopolysaccharide-Induced Production of Nitric Oxide, Prostaglandin E2, and Pro-inflammatory Cytokines in RAW 264.7 Macrophages

Limonene Suppresses Lipopolysaccharide-Induced Production of Nitric Oxide, Prostaglandin E2, and Pro-inflammatory Cytokines in RAW 264.7 Macrophages

Eudesmane-Type Sesquiterpene Lactones Inhibit Nuclear Translocation of the Nuclear Factor κB Subunit RelB in Response to a Lymphotoxin β Stimulation

Cardenolide Aglycones Inhibit Tumor Necrosis Factor α-Induced Expression of Intercellular Adhesion Molecule-1 at the Translation Step by Blocking Na+/K+-ATPase

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