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Gliostatin/thymidine phosphorylase-regulated vascular endothelial growth-factor production in human fibroblast-like synoviocytes

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Abstract

Gliostatin/thymidine phosphorylase (GLS/TP) is known to have angiogenic and arthritogenic activities. The purpose of this study was to elucidate whether GLS/TP is involved in the regulation of the angiogenic cytokine vascular endothelial growth factor (VEGF) in rheumatoid arthritis (RA). Fibroblast-like synoviocytes (FLSs) from patients with RA were cultured and stimulated with recombinant human GLS (rHuGLS) and interleukin (IL)-1β. Immunohistochemistry showed that GLS/TP and VEGF were detectable in the synovial lining cells. In cultured FLSs, both VEGF mRNA and protein levels were markedly increased by rHuIL-1β treatment. rHuGLS increased VEGF mRNA expression in a dose-dependent manner. We detected high concentrations of VEGF165 protein in culture supernatants from FLSs treated with rHuGLS (300 ng/ml), which were comparable to GLS levels found in synovial fluid of RA patients. These findings indicate that GLS/TP and VEGF have synergistic effects on angiogenesis in rheumatoid synovitis, and that GLS/TP has a role in regulating VEGF.

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Acknowledgments

This research was supported in part by a Grant-in-Aid for Scientific Research (C) from the Ministry of Education, Science, Sports and Culture of Japan, a Grant-in-Aid for Research from Nagoya City University, Japan, and a Grant-in-Aid for Aichi D.R.G. Foundation, Japan.

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Authors and Affiliations

  1. Department of Musculoskeletal Medicine, Nagoya City University Graduate School of Medical Sciences, Kawasumi 1, Mizuho chou, Mizuho-Ku, Nagoya, 467-8601, Japan

    Tomohiro Tanikawa, Yuko Waguri-Nagaya, Takuma Kusabe & Takanobu Otsuka

  2. Department of Molecular Neurobiology, Nagoya City University Graduate School of Medical Sciences, Mizuho-Ku, Nagoya, 467-8601, Japan

    Takuma Kusabe, Mineyoshi Aoyama & Kiyofumi Asai

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  1. Tomohiro Tanikawa
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  2. Yuko Waguri-Nagaya
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  3. Takuma Kusabe
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  4. Mineyoshi Aoyama
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  5. Kiyofumi Asai
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  6. Takanobu Otsuka
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Correspondence to Yuko Waguri-Nagaya.

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Tanikawa, T., Waguri-Nagaya, Y., Kusabe, T. et al. Gliostatin/thymidine phosphorylase-regulated vascular endothelial growth-factor production in human fibroblast-like synoviocytes. Rheumatol Int 27, 553–559 (2007). https://doi.org/10.1007/s00296-006-0258-5

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  • DOI: https://doi.org/10.1007/s00296-006-0258-5

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