kn-93 and Arthritis--Rheumatoid

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.. Rheumatoid synovial fibroblasts (RSF) were cultured under pro-inflammatory (IL-1beta stimulation) and hypoxic conditions. Protein and mRNA expression of HIF-1alpha and the effects of inhibitors of the CaMKII-, PI3K-, and ERK pathway on VEGF and IL-6 production were analyzed.. Stimulation under hypoxic conditions induced higher expression of HIF-1alpha and VEGF mRNA than treatment with either IL-1beta or hypoxia alone. However, incubation with a specific CaMKII inhibitor did not result in reduced VEGF production in RSF.. CaMKII activation has been reported to be involved in HIF-1alpha stabilization, but incubation with SMP-114, a specific CaMKII inhibitor, had no effect on HIF-1-induced VEGF production by rheumatoid synovial fibroblasts.

Topics: Arthritis, Rheumatoid; Benzylamines; Blotting, Western; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Calcium-Calmodulin-Dependent Protein Kinases; Cell Hypoxia; Cells, Cultured; Chromones; Enzyme-Linked Immunosorbent Assay; Fibroblasts; Flavonoids; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Interleukin-1beta; Interleukin-6; Morpholines; Phosphatidylinositol 3-Kinases; Phosphoinositide-3 Kinase Inhibitors; Protein Kinase Inhibitors; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sulfonamides; Synovial Membrane; Vascular Endothelial Growth Factor A