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Hyaluronan production in human rheumatoid fibroblastic synovial lining cells is increased by interleukin 1β but inhibited by transforming growth factor β1
  1. Makoto Kawakami,
  2. Kimihiro Suzuki,
  3. Yasunori Matsuki,
  4. Toshiaki Ishizuka,
  5. Toshihiko Hidaka,
  6. Tatsuya Konishi,
  7. Mitsuyo Matsumoto,
  8. Koji Kataharada,
  9. Haruo Nakamura
  1. Internal Medicine I, National Defence Medical College, Saitama, Japan
  1. Dr M Kawakami, Internal Medicine I, National Defence Medical College Namiki 3–2, Tokorozawa, Saitama, 359–8513, Japan.

Abstract

OBJECTIVES To investigate the regulatory roles of interleukin 1β (IL1β), tumour necrosis factor α (TNFα), interferon γ (IFNγ) or transforming growth factor β1 (TGFβ1) on hyaluronan (HA) synthesis by human fibroblastic synovial lining cells.

METHODS Concentrations of HA in culture supernatants of fibroblastic synovial lining cell line (RAMAK-1 cell line) with or without stimulation by IL1β, TNFα, IFNγ or TGFβ1 were measured by sandwich binding protein assay. Levels of HA synthase mRNA of the cells with or without stimulation were detected by reverse transcribed polymerase chain reaction. Molecular weights of HA in the culture supernatants of the cells with or without stimulation were measured using high performance gel permeation liquid chromatography.

RESULTS HA synthesis by the cells was not significantly augmented by TNFα or by IFNγ. It was significantly stimulated by IL1β but inhibited by TGFβ1. Molecular weights of HA in the culture supernatants of the cells were unchanged by stimulation with TNFα. They were remarkably increased by stimulation with IL1β and IFNγ, but reduced with TGFβ1.

CONCLUSION IL1β is an up regulator of HA synthesis, while TGFβ1 is a down regulator. HA production in the synovial lining cells of inflamed joints (for example, rheumatoid arthritis) might be regulated by the balance of these cytokines.

  • synovial lining cells
  • hyaluronan, interleukin 1β
  • transforming growth factor β1

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