Shingu M, Isayama T, Yasutake C, Naono T, Nobunaga M, Tomari K, Horie K, Goto Y
Department of Clinical Immunology, Kyushu University, Beppu, Japan.
Inflammation. 1994 Dec;18(6):613-23. doi: 10.1007/BF01535259.
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-1 beta-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-1 beta. IL-6 significantly suppressed cartilage matrix degradation produced spontaneously or by IL-1 beta stimulation in chondrocytes. IL-6 inhibited superoxide production by chondrocytes both in IL-1 beta-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 radical-mediated 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.
有人提出，白细胞介素-1（IL-1）通过诸如胶原酶等金属蛋白酶导致软骨基质降解，且这种降解受金属蛋白酶抑制剂调控。在本研究中，研究了白细胞介素-6（IL-6）和氧自由基清除剂对软骨基质降解的影响。超氧化物歧化酶、过氧化氢酶或蛋氨酸在白细胞介素-1β（IL-1β）刺激和未刺激的实验条件下均显著抑制软骨基质降解。10 mM乙二胺四乙酸（EDTA）和100 nM金属蛋白酶组织抑制剂（TIMP）均显著抑制软骨基质降解。添加蛋氨酸显著抑制IL-1β刺激的软骨细胞培养上清液中产生的胶原酶活性。IL-6显著抑制软骨细胞自发产生或由IL-1β刺激产生 的软骨基质降解。在IL-1β刺激或未刺激的条件下，IL-6均抑制软骨细胞产生超氧化物。这些结果表明，氧自由基参与旁分泌和自分泌IL-1机制介导的软骨基质降解，且软骨细胞中氧自由基介导的胶原酶激活可能解释了氧自由基参与软骨基质降解的机制。IL-6抑制软骨细胞产生超氧化物，从而抑制软骨基质降解。
