Gene interactions and pathways from curated databases and text-mining
J Immunol 2000, PMID: 10820260

Vesnarinone suppresses TNF-induced activation of NF-kappa B, c-Jun kinase, and apoptosis.

Manna, S K; Aggarwal, B B

Vesnarinone, a synthetic quinolinone derivative used in the treatment of cardiac failure, exhibits immunomodulatory, anti-inflammatory, and cell growth regulatory properties. The mechanisms underlying these properties are not understood, but due to the critical role of nuclear transcription factor NF-kappa B in these responses, we hypothesized that vesnarinone must modulate NF-kappa B activation. We investigated the effect of vesnarinone on NF-kappa B activation induced by inflammatory agents. Vesnarinone blocked TNF-induced activation of NF-kappa B in a concentration- and time-dependent manner. This effect was mediated through inhibition of phosphorylation and degradation of I kappa B alpha, an inhibitor of NF-kappa B. The effects of vesnarinone were not cell type specific, as it blocked TNF-induced NF-kappa B activation in a variety of cells. NF-kappa B-dependent reporter gene transcription activated by TNF was also suppressed by vesnarinone. The TNF-induced NF-kappa B activation cascade involving TNF receptor 1-TNF receptor associated death domain-TNF receptor associated factor 2 NF-kappa B-inducing kinase-IKK was interrupted at the TNF receptor associated factor 2 and NF-kappa B-inducing kinase sites by vesnarinone, thus suppressing NF-kappa B reporter gene expression. Vesnarinone also blocked NF-kappa B activation induced by several other inflammatory agents, inhibited the TNF-induced activation of transcription factor AP-1, and suppressed the TNF-induced activation of c-Jun N-terminal kinase and mitogen-activated protein kinase kinase. TNF-induced cytotoxicity, caspase activation, and lipid peroxidation were also abolished by vesnarinone. Overall, our results indicate that vesnarinone inhibits activation of NF-kappa B and AP-1 and their associated kinases. This may provide a molecular basis for vesnarinone's ability to suppress inflammation, immunomodulation, and growth regulation.

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Text Mining Data

NF-kappa B → TNF: " Vesnarinone suppresses TNF induced activation of NF-kappa B , c-Jun kinase, and apoptosis "

NF-kappa B → TNF: " Vesnarinone blocked TNF induced activation of NF-kappa B in a concentration- and time dependent manner "

NF-kappa B ⊣ I kappa B alpha: " This effect was mediated through inhibition of phosphorylation and degradation of I kappa B alpha , an inhibitor of NF-kappa B "

NF-kappa B → TNF: " The effects of vesnarinone were not cell type specific, as it blocked TNF induced NF-kappa B activation in a variety of cells "

AP-1 ⊣ TNF: " Vesnarinone also blocked NF-kappa B activation induced by several other inflammatory agents, inhibited the TNF induced activation of transcription factor AP-1 , and suppressed the TNF induced activation of c-Jun N-terminal kinase and mitogen activated protein kinase kinase "

AP-1 ⊣ mitogen activated protein kinase kinase: " Vesnarinone also blocked NF-kappa B activation induced by several other inflammatory agents, inhibited the TNF induced activation of transcription factor AP-1 , and suppressed the TNF induced activation of c-Jun N-terminal kinase and mitogen activated protein kinase kinase "

AP-1 ⊣ NF-kappa B: " Vesnarinone also blocked NF-kappa B activation induced by several other inflammatory agents, inhibited the TNF induced activation of transcription factor AP-1 , and suppressed the TNF induced activation of c-Jun N-terminal kinase and mitogen activated protein kinase kinase "

mitogen activated protein kinase kinase ⊣ TNF: " Vesnarinone also blocked NF-kappa B activation induced by several other inflammatory agents, inhibited the TNF induced activation of transcription factor AP-1, and suppressed the TNF induced activation of c-Jun N-terminal kinase and mitogen activated protein kinase kinase "

NF-kappa B ⊣ TNF: " Vesnarinone also blocked NF-kappa B activation induced by several other inflammatory agents, inhibited the TNF induced activation of transcription factor AP-1, and suppressed the TNF induced activation of c-Jun N-terminal kinase and mitogen activated protein kinase kinase "

caspase → TNF: " TNF induced cytotoxicity, caspase activation, and lipid peroxidation were also abolished by vesnarinone "

Manually curated Databases

No curated data.