title: Inflammatory cytokine-induced expression of vasohibin-1 by rheumatoid synovial fibroblasts.
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.
authors.affiliation: Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Miyake
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Nishida
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Kadota
authors.forename: Hiroko
authors.initials: H
authors.lastname: Yamasaki
authors.forename: Tatsuyo
authors.initials: T
authors.lastname: Nasu
authors.forename: Daisuke
authors.initials: D
authors.lastname: Saitou
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Tanabe
authors.forename: Hikaru
authors.initials: H
authors.lastname: Sonoda
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Sato
authors.forename: Yohei
authors.initials: Y
authors.lastname: Maeshima
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Makino
mesh_terms: D000368:Aged; D020533:Angiogenesis Inhibitors / Q000378:metabolism*; D018952:Antigens, CD34 / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology*; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000276:immunology / Q000473:pathology; D013583:Synovial Membrane / Q000166:cytology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D018952:Antigens, CD34; D018797:Cell Cycle Proteins; D016207:Cytokines; C493181:VASH1 protein, human; D042461:Vascular Endothelial Growth Factor A