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首页> 外文期刊>Cytokine >IL-10 overexpression differentially affects cartilage matrix gene expression in response to TNF-alpha in human articular chondrocytes in vitro.
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IL-10 overexpression differentially affects cartilage matrix gene expression in response to TNF-alpha in human articular chondrocytes in vitro.

机译:IL-10的过表达在体外对人关节软骨细胞中的TNF-α响应有差异地影响软骨基质基因的表达。

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Cartilage-specific extracellular matrix synthesis is the prerequisite for chondrocyte survival and cartilage function, but is affected by the pro-inflammatory cytokine TNF-alpha in arthritis. The aim of the present study was to characterize whether the immunoregulatory cytokine IL-10 might modulate cartilage matrix and cytokine expression in response to TNF-alpha. Primary human articular chondrocytes were treated with either recombinant IL-10, TNF-alpha or a combination of both (at 10ng/mL each) or transduced with an adenoviral vector overexpressing human IL-10 and subsequently stimulated with 10ng/ml TNF-alpha for 6 or 24h. The effects of IL-10 on the cartilage-specific matrix proteins collagen type II, aggrecan, matrix-metalloproteinases (MMP)-3, -13 and pro-inflammatory cytokines were evaluated by real-time RT-PCR and immunohistochemistry. Transduced chondrocytes overexpressed high levels of IL-10 which significantly up-regulated collagen type II expression. TNF-alpha suppressed collagen type II andaggrecan, but increased MMP and cytokine expression in chondrocytes compared to the non-stimulated controls. The TNF-alpha mediated down-regulation of aggrecan expression was significantly antagonized by IL-10 overexpression, whereas the suppression of collagen type II was barely affected. The MMP-13 and IL-1beta expression by TNF-alpha was slightly reduced by IL-10. These results suggest that IL-10 overexpression modulates some catabolic features of TNF-alpha in chondrocytes.
机译:软骨特异性细胞外基质合成是软骨细胞存活和软骨功能的先决条件,但受到关节炎中促炎性细胞因子TNF-α的影响。本研究的目的是鉴定免疫调节细胞因子IL-10是否可以调节对TNF-α的软骨基质和细胞因子的表达。用重组IL-10,TNF-α或两者的组合(每次10ng / mL)处理原代人关节软骨细胞,或用过表达人IL-10的腺病毒载体转导,然后用10ng / mlTNF-α刺激。 6或24小时。通过实时RT-PCR和免疫组织化学评估IL-10对软骨特异性基质蛋白II型胶原蛋白,聚集蛋白聚糖,基质金属蛋白酶(MMP)-3,-13和促炎细胞因子的影响。转导的软骨细胞过表达高水平的IL-10,后者显着上调了II型胶原蛋白的表达。与未刺激的对照组相比,TNF-α抑制II型胶原和aggrecan,但增加了软骨细胞中MMP和细胞因子的表达。 TNF-α介导的聚集蛋白聚糖表达的下调被IL-10过表达明显拮抗,而II型胶原蛋白的抑制作用几乎没有受到影响。 IL-10使TNF-α的MMP-13和IL-1beta表达略有降低。这些结果表明,IL-10过度表达可调节软骨细胞中TNF-α的某些分解代谢功能。

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