Role for CaMKII Inhibition in Rheumatoid Arthritis Effects on HIF-1-Induced VEGF Production by Rheumatoid Synovial Fibroblasts

Johanna Westra*, Elisabeth Brouwer, Erwin Bouwman, Berber Doornbos-van der Meer, Marcel D. Posthumus, Miek A. van Leeuwen, Pieter C. Limburg, Yutaka Ueda, Cees G. M. Kallenberg

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

15 Citaten (Scopus)

Samenvatting

Background and aims: The present study was designed to investigate the effects of a novel CaMKII inhibitor SMP-114, which was effective in a collagen-induced arthritis model in rats, on rheumatoid synovial fibroblasts. Methods: Rheumatoid synovial fibroblasts (RSF) were cultured under pro-inflammatory (IL-1 beta stimulation) and hypoxic conditions. Protein and mRNA expression of HIF-1 alpha and the effects of inhibitors of the CaMKII-, PI3K-, and ERK pathway on VEGF and IL-6 production were analyzed. Results: Stimulation under hypoxic conditions induced higher expression of HIF-1 alpha and VEGF mRNA than treatment with either IL-1 beta or hypoxia alone. However, incubation with a specific CaMKII inhibitor did not result in reduced VEGF production in RSF. Conclusions: CaMKII activation has been reported to be involved in HIF-1 alpha stabilization, but incubation with SMP-114, a specific CaMKII inhibitor, had no effect on HIF-1-induced VEGF production by rheumatoid synovial fibroblasts.

Originele taal-2English
TitelCONTEMPORARY CHALLENGES IN AUTOIMMUNITY
RedacteurenY Shoenfeld, ME Gershwin
Plaats van productieMALDEN
UitgeverijBlackwell Publishing
Pagina's706-711
Aantal pagina's6
ISBN van geprinte versie978-1-57331-762-7
DOI's
StatusPublished - 2009
Evenement6th International Congress on Autoimmunity - , Portugal
Duur: 10-sep-200814-sep-2008

Publicatie series

NaamAnnals of the New York Academy of Sciences
UitgeverijWILEY-BLACKWELL
Volume1173
ISSN van geprinte versie0077-8923

Other

Other6th International Congress on Autoimmunity
LandPortugal
Periode10/09/200814/09/2008

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