Interleukin 17 induces cartilage collagen breakdown: novel synergistic effects in combination with proinflammatory cytokines
Interleukin 17 induces cartilage collagen breakdown: novel synergistic effects in combination with proinflammatory cytokines
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DOI：
10.1136/ard.61.8.704
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发表时间：
2002-08-01
影响因子：
27.4
通讯作者：
Rowan, AD
中科院分区：
文献类型：
--
作者：
Koshy, PJ;Henderson, N;Rowan, AD
目的：研究T细胞特异性白细胞介素17（IL 17）对软骨Ⅱ型胶原释放的影响。IL 17的能力，协同与其他促炎介质，以诱导胶原蛋白从软骨中释放，什么样的效果抗炎剂对这个过程中，也assessed.Methods：IL 17单独，或与IL 1，IL 6，制瘤素M（OSM），或肿瘤坏死因子α（TNF α）的组合，被添加到牛鼻软骨外植体培养。测定蛋白多糖和胶原蛋白的释放。通过生物测定法测定胶原溶解活性。软骨保护作用的IL 4，IL 13，转化生长因子β 1（TGF β 1）和胰岛素样生长因子-1（IGF 1）进行了评估，包括在外植体culture.Results：IL 1 - 7单独刺激蛋白多糖和11型胶原从牛鼻软骨外植体的剂量依赖性释放。次优剂量的IL 17与TNF α、IL 1、OSM和IL 6有效协同促进胶原降解。这种胶原蛋白的释放被金属蛋白酶-1和BB-94（一种合成的金属蛋白酶抑制剂）的组织抑制剂完全抑制，并且被IL 4、IL 13、TGF β 1和IGF 1显著降低。在IL 17处理的软骨细胞中，检测到基质金属蛋白酶（MMP）-1，MMP-3和MMP-13的mRNA表达。此外，这些MMPs的协同诱导时，看到IL 17与其他促炎cytokines.Conclusions：IL 17可以，单独和协同结合与其他促炎细胞因子，促进软骨细胞介导的MMP依赖的11型胶原从软骨释放。由于所有这些促炎细胞因子的水平在类风湿关节液中升高，因此本研究表明IL 17可能在炎性关节疾病中充当软骨胶原分解的有效上游介质。
Objective: To investigate whether interleukin 17 (IL17), derived specifically from T cells, can promote type II collagen release from cartilage. The ability of IL17 to synergise with other proinflammatory mediators to induce collagen release from cartilage, and what effect anti-inflammatory agents had on this process, was also assessed.Methods: IL17 alone, or in combination with IL1, IL6, oncostatin M (OSM), or tumour necrosis factor alpha (TNFalpha), was added to bovine nasal cartilage explant cultures. Proteoglycan and collagen release were determined. Collagenolytic activity was determined by bioassay. Chondroprotective effects of IL4, IL13, transforming growth factor beta1 (TGFbeta1) and insulin-like growth factor-1 (IGF1) were assessed by inclusion in the explant cultures.Results: IL1 7 alone stimulated a dose dependent release of proteoglycan and type 11 collagen from bovine nasal cartilage explants. Suboptimal doses of IL17 synergised potently with TNFalpha, IL1, OSM, and IL6 to promote collagen degradation. This collagen release was completely inhibited by tissue inhibitor of metalloproteinase-1 and BB-94 (a synthetic metalloproteinase inhibitor), and was significantly reduced by IL4, IL13, TGFbeta1, and IGF1. In IL17 treated chondrocytes, mRNA expression for matrix metalloproteinase (MMP)-1, MMP-3, and MMP-13 was detected. Moreover, a synergistic induction of these MMPs was seen when IL17 was combined with other proinflammatory cytokines.Conclusions: IL17 can, alone and synergistically in combination with other proinflammatory cytokines, promote chondrocyte mediated MMP dependent type 11 collagen release from cartilage. Because levels of all these proinflammatory cytokines are raised in rheumatoid synovial fluids, this study suggests that IL17 may act as a potent upstream mediator of cartilage collagen breakdown in inflammatory joint diseases.