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

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingConference contributionAcademicpeer-review

15 Citations (Scopus)

Abstract

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.

Original languageEnglish
Title of host publicationCONTEMPORARY CHALLENGES IN AUTOIMMUNITY
EditorsY Shoenfeld, ME Gershwin
Place of PublicationMALDEN
PublisherBlackwell Publishing
Pages706-711
Number of pages6
ISBN (Print)978-1-57331-762-7
DOIs
Publication statusPublished - 2009
Event6th International Congress on Autoimmunity - , Portugal
Duration: 10-Sep-200814-Sep-2008

Publication series

NameAnnals of the New York Academy of Sciences
PublisherWILEY-BLACKWELL
Volume1173
ISSN (Print)0077-8923

Other

Other6th International Congress on Autoimmunity
Country/TerritoryPortugal
Period10/09/200814/09/2008

Keywords

  • CaMKII
  • synovial fibroblast
  • VEGF
  • PROTEIN-KINASE-II
  • HYPOXIA
  • ACTIVATION
  • ANGIOGENESIS
  • MACROPHAGES
  • EXPRESSION
  • CYTOKINE
  • CELLS

Cite this