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Role of oxygen radicals and IL-6 in IL-1-dependent cartilage matrix degradation

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Abstract

It has been suggested that IL-1 produces cartilage matrix degradation by metalloproteinases such as collagenase and that such degradation is regulated by metalloproteinase inhibitors. In the present study, the effects of IL-6 and oxygen radical scavengers on cartilage matrix degradation were studied. Superoxide dismutase, catalase, or methionine all significantly inhibited cartilage matrix degradation both in IL-1β-stimulated and unstimulated experimental conditions. Both 10 mM EDTA and 100 nM tissue inhibitor of metalloproteinase (TIMP) significantly inhibited cartilage matrix degradation. The addition of methionine significantly inhibited collagenase activity produced in the culture supernatants of chondrocytes stimulated with IL-1β. IL-6 significantly suppressed cartilage matrix degradation produced spontaneously or by IL-1β stimulation in chondrocytes. IL-6 inhibited superoxide production by chondrocytes both in IL-1β-stimulated or unstimulated conditions. These results suggest that oxygen radicals are involved in cartilage matrix degradation mediated by both paracrine and autocrine IL-1 mechanisms and that oxygen radicalmediated activation of collagenase in chondrocytes may explain the mechanisms of how oxygen radicals are involved in cartilage matrix degradation. IL-6 inhibited superoxide production in chondrocytes and thus inhibited cartilage matrix degradation.

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Authors and Affiliations

  1. Department of Clinical Immunology, Medical Institute of Bioregulation, Kyushu University 69, Beppu, Japan

    Masao Shingu, Tetsurou Isayama & Masashi Nobunaga

  2. Department of Orthopedics, Beppu National Hospital, Beppu, Japan

    Tetsurou Isayama, Chie Yasutake & Takashi Naono

  3. Department of Orthopedics, New Beppu Hospital, Beppu, Japan

    Kazuhide Tomari

  4. Tokyo Research Institute of Seikagaku-Kogyo Co. Ltd., Tokyo, Japan

    Katsuyuki Horie & Yukiko Goto

Authors
  1. Masao Shingu
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  2. Tetsurou Isayama
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  3. Chie Yasutake
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  4. Takashi Naono
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  5. Masashi Nobunaga
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  6. Kazuhide Tomari
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  7. Katsuyuki Horie
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  8. Yukiko Goto
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Shingu, M., Isayama, T., Yasutake, C. et al. Role of oxygen radicals and IL-6 in IL-1-dependent cartilage matrix degradation. Inflammation 18, 613–623 (1994). https://doi.org/10.1007/BF01535259

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