Inflammatory cytokine-induced expression of vasohibin-1 by rheumatoid synovial fibroblasts

Acta Med Okayama. 2009 Dec;63(6):349-58. doi: 10.18926/AMO/31820.

Abstract

Angiogenesis is an essential event in the development of synovial inflammation in rheumatoid arthritis (RA). The aim of the current study was to investigate the expression of vasohibin-1, a novel endothelium-derived vascular endothelial growth factor (VEGF)-inducible angiogenesis inhibitor, in the RA synovium, and to test the effect of inflammatory cytokines on the expression of vasohibin-1 by RA synovial fibroblasts (RASFs). Synovial tissue samples were obtained at surgery from patients with osteoarthritis (OA) and RA, and subjected to immunohistochemistry to investigate the expression and distribution of vasohibin-1 relevant to the degree of synovial inflammation. In an in vitro analysis, RASFs were used to examine the expression of vasohibin-1 and VEGF mRNA by real-time PCR after stimulation with VEGF or inflammatory cytokines under normoxic or hypoxic conditions. The immunohistochemical results showed that vasohibin-1 was expressed in synovial lining cells, endothelial cells, and synovial fibroblasts. In synovial tissue, there was a significant correlation between the expression of vasohibin-1 and histological inflammation score (p=0.002, r=0.842). In vitro, stimulation with VEGF induced the expression of vasohibin-1 mRNA in RASFs under normoxic conditions, and stimulation with cytokines induced vasohibin-1 mRNA expression under a hypoxic condition. These results suggest that vasohibin-1 was expressed in RA synovial tissue and might be regulated by inflammatory cytokines.

MeSH terms

  • Aged
  • Angiogenesis Inhibitors / metabolism*
  • Antigens, CD34 / metabolism
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / pathology
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cells, Cultured
  • Cytokines / immunology*
  • Female
  • Fibroblasts / cytology
  • Fibroblasts / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Osteoarthritis / immunology
  • Osteoarthritis / pathology
  • Synovial Membrane / cytology*
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Angiogenesis Inhibitors
  • Antigens, CD34
  • Cell Cycle Proteins
  • Cytokines
  • VASH1 protein, human
  • Vascular Endothelial Growth Factor A