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The anti-malaria agent artesunate inhibits expression of vascular endothelial growth factor and hypoxia-inducible factor-1 alpha in human rheumatoid arthritis fibroblast-like synoviocyte
Rheumatology International, 10/30/09

He Y et al. – Increasing evidence indicates that the anti-malarial agent artemisinin and its derivatives may exert anti-angiogenic effect. In the present study, we explored the effect of artesunate, a artemisinin derivative, on TNF?- and hypoxia-induced expression of hypoxia inducible factor-1? (HIF-1?) and secretion of vascular endothelial growth factor (VEGF) and inteleukin-8 (IL-8) in human rheumatoid arthritis fibroblast-like synoviocytes (RA FLS), and further investigated the signal mechanism by which this compound modulates HIF-1?, VEGF and IL-8 expression.

Methods

RA FLS obtained from patients with active RA were pretreated with artesunate, and then stimulated with TNF &alpha and hypoxia
Production of VEGF and IL-8 measured by ELISA
Nuclear location of HIF-1 &alpha measured by confocal fluorescence microscopy
HIF-1 &alpha and other signal transduction proteins expression was measured by Western blot

Results

Artesunate decreased secretion of VEGF and IL-8 from TNF &alpha- or hypoxia-stimulated RA FLS in dose-dependent manner
Artesunate prevented Akt phosphorylation, but did not find evidence that phosphorylation of p38 and ERK was affected
TNF &alpha- or hypoxia-induced secretion of VEGF and IL-8 and expression of HIF-1 &alpha hampered by treatment with PI3 kinase inhibitor LY294002, suggesting that inhibition of PI3 kinase/Akt activation might inhibit VEGF and IL-8 secretion and HIF-1 &alpha expression induced by TNF &alpha or hypoxia

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