TNF-alpha modulates angiopoietin-1 expression in rheumatoid synovial fibroblasts via the NF-kappa B signalling pathway.
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.
Scott
B B
BB
GlaxoSmithKline Pharmaceuticals, Neurobiology, Department of Neuroscience, Milan, Italy. bscott@concurrentpharma.com
Zaratin
P F
PF
Gilmartin
A G
AG
Hansbury
M J
MJ
Colombo
A
A
Belpasso
C
C
Winkler
J D
JD
Jackson
J R
JR
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*
D042683:Angiopoietin-1; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha