The role of synovial macrophages and macrophage-produced cytokines in driving aggrecanases, matrix metalloproteinases, and other destructive and inflammatory responses in osteoarthritis.
The role of synovial macrophages and macrophage-produced cytokines in driving aggrecanases, matrix metalloproteinases, and other destructive and inflammatory responses in osteoarthritis.
复制标题
滑膜巨噬细胞和巨噬细胞产生的细胞因子在驱动聚集蛋白聚糖酶、基质金属蛋白酶和骨关节炎中其他破坏性和炎症反应中的作用。
DOI：
10.1186/ar2099
复制
发表时间：
2006
影响因子：
4.9
通讯作者：
Hughes CE
中科院分区：
文献类型：
--
作者：
Bondeson J;Wainwright SD;Lauder S;Amos N;Hughes CE
越来越多的证据表明滑膜炎在骨关节炎的进展中起作用，发炎的滑膜产生过多的细胞因子和生长因子会影响降解酶的产生以及软骨的破坏。在这项研究中，我们探讨滑膜巨噬细胞及其主要促炎细胞因子白细胞介素（IL）-1和肿瘤坏死因子 -α（TNF -α）在引发骨关节炎滑膜炎以及影响其他促炎和抗炎细胞因子的产生、基质金属蛋白酶的产生和聚集蛋白聚糖酶在骨关节炎滑膜中的表达方面的作用。我们建立了一个来自接受膝关节或髋关节置换术患者的消化后的骨关节炎滑膜的滑膜细胞培养模型。通过抗CD14偶联的磁珠，可以从这些培养物中特异性去除骨关节炎滑膜巨噬细胞。去除CD14⁺的培养物不再产生大量由巨噬细胞衍生的细胞因子，如IL -1和TNF -α。有趣的是，几种主要由滑膜成纤维细胞产生的细胞因子，如IL -6和IL -8（p < 0.001）以及基质金属蛋白酶1和3（p < 0.01）也显著下调。为了研究相关机制，我们接着在这些骨关节炎滑膜细胞培养物中对IL -1和/或TNF -α进行特异性下调。结果表明，需要中和IL -1和TNF -α才能达到一定程度的细胞因子（IL -6、IL -8和单核细胞趋化蛋白 -1）和基质金属蛋白酶（1、3、9和13）抑制，这通过酶联免疫吸附测定和逆转录 - 聚合酶链反应（RT - PCR）评估，与在去除CD14⁺的培养物中观察到的情况相似。另一个有趣的观察结果是，在这些骨关节炎滑膜细胞培养物中，与类风湿关节炎的情况相反，IL -1β的产生不依赖于TNF -α。通过RT - PCR，我们还证明了虽然含血小板反应蛋白基序的解聚素和金属蛋白酶4（ADAMTS4）聚集蛋白聚糖酶主要由TNF -α驱动，但ADAMTS5不受IL -1和/或TNF -α中和的影响。这些结果表明，在骨关节炎滑膜中，炎症反应和破坏反应在很大程度上都依赖于巨噬细胞，并且这些效应是由细胞因子驱动的，通过IL -1和TNF -α的共同作用。
There is an increasing body of evidence that synovitis plays a role in the progression of osteoarthritis and that overproduction of cytokines and growth factors from the inflamed synovium can influence the production of degradative enzymes and the destruction of cartilage. In this study, we investigate the role of synovial macrophages and their main proinflammatory cytokines, interleukin (IL)-1 and tumour necrosis factor-alpha (TNF-α), in driving osteoarthritis synovitis and influencing the production of other pro- and anti-inflammatory cytokines, production of matrix metalloproteinases, and expression of aggrecanases in the osteoarthritis synovium. We established a model of cultures of synovial cells from digested osteoarthritis synovium derived from patients undergoing knee or hip arthroplasties. By means of anti-CD14-conjugated magnetic beads, specific depletion of osteoarthritis synovial macrophages from these cultures could be achieved. The CD14+-depleted cultures no longer produced significant amounts of macrophage-derived cytokines like IL-1 and TNF-α. Interestingly, there was also significant downregulation of several cytokines, such as IL-6 and IL-8 (p < 0.001) and matrix metalloproteinases 1 and 3 (p < 0.01), produced chiefly by synovial fibroblasts. To investigate the mechanisms involved, we went on to use specific downregulation of IL-1 and/or TNF-α in these osteoarthritis cultures of synovial cells. The results indicated that neutralisation of both IL-1 and TNF-α was needed to achieve a degree of cytokine (IL-6, IL-8, and monocyte chemoattractant protein-1) and matrix metalloproteinase (1, 3, 9, and 13) inhibition, as assessed by enzyme-linked immunosorbent assay and by reverse transcription-polymerase chain reaction (RT-PCR), similar to that observed in CD14+-depleted cultures. Another interesting observation was that in these osteoarthritis cultures of synovial cells, IL-1β production was independent of TNF-α, in contrast to the situation in rheumatoid arthritis. Using RT-PCR, we also demonstrated that whereas the ADAMTS4 (a disintegrin and metalloprotease with thrombospondin motifs 4) aggrecanase was driven mainly by TNF-α, ADAMTS5 was not affected by neutralisation of IL-1 and/or TNF-α. These results suggest that, in the osteoarthritis synovium, both inflammatory and destructive responses are dependent largely on macrophages and that these effects are cytokine-driven through a combination of IL-1 and TNF-α.
登录
查看更多内容
影响因子：
4.8
作者：
Abbaszade, I;Liu, RQ;Burn, TC
通讯作者：
Burn, TC
影响因子：
6.9
作者：
Caterson, B;Flannery, CR;Little, CB
通讯作者：
Little, CB
影响因子：
--
作者：
Andreakos, E;Smith, C;Foxwell, BM
通讯作者：
Foxwell, BM
影响因子：
--
作者：
Haywood, L;McWilliams, DF;Walsh, DA
通讯作者：
Walsh, DA
DOI：
10.1073/pnas.96.10.5668
发表时间：
1999-05-11
影响因子：
11.1
作者：
Bondeson, J;Foxwell, B;Feldmann, M
通讯作者：
Feldmann, M