cep-11004 and Inflammation

cep-11004 has been researched along with Inflammation* in 1 studies

Other Studies

1 other study(ies) available for cep-11004 and Inflammation

ArticleYear
Specific modulation of astrocyte inflammation by inhibition of mixed lineage kinases with CEP-1347.
    Journal of immunology (Baltimore, Md. : 1950), 2004, Aug-15, Volume: 173, Issue:4

    Inflammatory conversion of murine astrocytes correlates with the activation of various MAPK, and inhibition of terminal MAPKs like JNK or p38 dampens the inflammatory reaction. Mixed lineage kinases (MLKs), a family of MAPK kinase kinases, may therefore be involved in astrocyte inflammation. In this study, we explored the effect of the MLK inhibitors CEP-1347 and CEP-11004 on the activation of murine astrocytes by either TNF plus IL-1 or by a complete cytokine mix containing additional IFN-gamma. The compounds blocked NO-, PG-, and IL-6 release with a median inhibitory concentration of approximately 100 nM. This activity correlated with a block of the JNK and the p38 pathways activated in complete cytokine mix-treated astrocytes. Although CEP-1347 did not affect the activation of NF-kappaB, it blocked the expression of cyclooxygenase-2 and inducible NO synthase at the transcriptional level. Quantitative transcript profiling of 17 inflammation-linked genes revealed a specific modulation pattern of astrocyte activation by MLK inhibition, for instance, characterized by up-regulation of the anti-stress factors inhibitor of apoptosis protein-2 and activated transcription factor 4, no effect on manganese superoxide dismutase and caspase-11, and down-regulation of major inflammatory players like TNF, GM-CSF, urokinase-type plasminogen activator, and IL-6. In conclusion, MLK inhibitors like CEP-1347 are highly potent astrocyte immune modulators with a novel spectrum of activity.

    Topics: Animals; Astrocytes; Blotting, Western; Carbazoles; Cells, Cultured; Cyclooxygenase 2; Dose-Response Relationship, Drug; Enzyme Activation; Enzyme Inhibitors; Gene Expression; Immunoassay; In Situ Hybridization; Indoles; Inflammation; Interleukin-6; Isoenzymes; JNK Mitogen-Activated Protein Kinases; MAP Kinase Kinase 4; MAP Kinase Kinase Kinases; Mice; Mitogen-Activated Protein Kinase Kinases; NF-kappa B; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Polymerase Chain Reaction; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Transcription, Genetic

2004