Rheumatoid Arthritis Research Today is a free monthly online journal that collates and summarizes the latest research about Rheumatoid Arthritis, including details on treatment, symptoms, causes, medication.

TNF-alpha modulates angiopoietin-1 expression in rheumatoid synovial fibroblasts via the NF-kappa B signalling pathway.

Scott BB, Zaratin PF, Gilmartin AG, Hansbury MJ, Colombo A, Belpasso C, Winkler JD, Jackson JR

GlaxoSmithKline Pharmaceuticals, Neurobiology, Department of Neuroscience, Milan, Italy. bscott@concurrentpharma.com

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.

Published 7 February 2005 in Biochem Biophys Res Commun, 328(2): 409-14.
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