title: TNF-alpha modulates angiopoietin-1 expression in rheumatoid synovial fibroblasts via the NF-kappa B signalling pathway.
abstract: Angiopoietin-1 (Ang-1) is one of a family of ligands for the Tie-2 receptor which has been demonstrated to be involved in angiogenesis. Little is known about the regulation of Ang-1 gene expression. We have previously demonstrated that TNF-alpha is able to up-regulate the expression of Ang-1 mRNA in synovial fibroblasts. This present study investigated the signal transduction pathways involved in the TNF-alpha induced expression of Ang-1. TNF-alpha signals primarily through the p38, JNK, MAP kinase, and IKK pathways resulting in the activation of the transcription factors AP-1 and NF-kappa B. Experiments with inhibitors and siRNA for these various signal transduction pathways revealed that TNF-alpha stimulation of Ang-1 expression occurs via the NF-kappa B signal transduction pathway.
authors.affiliation: GlaxoSmithKline Pharmaceuticals, Neurobiology, Department of Neuroscience, Milan, Italy. bscott@concurrentpharma.com
authors.forename: B B
authors.initials: BB
authors.lastname: Scott
authors.forename: P F
authors.initials: PF
authors.lastname: Zaratin
authors.forename: A G
authors.initials: AG
authors.lastname: Gilmartin
authors.forename: M J
authors.initials: MJ
authors.lastname: Hansbury
authors.forename: A
authors.initials: A
authors.lastname: Colombo
authors.forename: C
authors.initials: C
authors.lastname: Belpasso
authors.forename: J D
authors.initials: JD
authors.lastname: Winkler
authors.forename: J R
authors.initials: JR
authors.lastname: Jackson
mesh_terms: D042683:Angiopoietin-1 / Q000378:metabolism*; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D042683:Angiopoietin-1; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha