Specific Modulation of Astrocyte Inflammation by Inhibition of Mixed Lineage Kinases with CEP-1347

• Published in: The Journal of immunology (1950) Vol. 173; no. 4; pp. 2762 - 2770
• Main Authors: Falsig, Jeppe, Porzgen, Peter, Lotharius, Julie, Leist, Marcel
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.08.2004
• Subjects: Animals; Astrocytes - drug effects; Astrocytes - enzymology; Astrocytes - immunology; Blotting, Western; Carbazoles - pharmacology; Cells, Cultured; Cyclooxygenase 2; Dose-Response Relationship, Drug; Enzyme Activation - drug effects; Enzyme Activation - immunology; Enzyme Inhibitors - pharmacology; Gene Expression - drug effects; Immunoassay; In Situ Hybridization; Indoles - pharmacology; Inflammation - immunology; Interleukin-6 - metabolism; Isoenzymes - drug effects; Isoenzymes - metabolism; JNK Mitogen-Activated Protein Kinases; MAP Kinase Kinase 4; MAP Kinase Kinase Kinases - drug effects; MAP Kinase Kinase Kinases - immunology; Mice; Mitogen-Activated Protein Kinase Kinases - drug effects; Mitogen-Activated Protein Kinase Kinases - metabolism; NF-kappa B - drug effects; NF-kappa B - metabolism; Nitric Oxide - metabolism; Nitric Oxide Synthase - drug effects; Nitric Oxide Synthase - metabolism; Nitric Oxide Synthase Type II; Polymerase Chain Reaction; Prostaglandin-Endoperoxide Synthases - drug effects; Prostaglandin-Endoperoxide Synthases - metabolism; Prostaglandins - metabolism; Transcription, Genetic - drug effects

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...