Exuberant expression of chemokine genes by adult human articular chondrocytes in response to IL-1β
Exuberant expression of chemokine genes by adult human articular chondrocytes in response to IL-1β
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DOI：
10.1016/j.joca.2008.04.027
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发表时间：
2008-12-01
影响因子：
7
通讯作者：
Patra, D.
中科院分区：
文献类型：
--
作者：
Sandell, L. J.;Xing, X.;Patra, D.
目的：与候选基因方法相比，更全面地了解白细胞介素 1 β (IL-1 β) 对成人关节软骨细胞基因表达的影响。设计：在含有 IL-1 β 的培养基中培养来自人膝关节软骨的软骨细胞。通过微阵列和逆转录酶-聚合酶链式反应分析来分析基因表达的变化。分析了转化生长因子 β-1 (TGF-β 1)、成纤维细胞生长因子 (FGF)-18 和骨形态发生蛋白 2 (BMP-2) 改变 IL-1 β 作用的能力。对转录因子结合基序差异表达基因的启动子区域进行了计算分析。结果：IL-1β处理的人软骨细胞显示粒细胞集落刺激因子-3、内皮白细胞粘附分子1和白血病抑制因子以及包括CXCL1、 CXCL2、CXCL3、CXCL5、CXCL6、CXCL8、CCL2、CCL3、CCL4、CCL5、CCL8、CCL20、CCL3L1、CX3CL1 和细胞因子 IL-6。正如预期的那样，基质金属蛋白酶 (MMP)-13 和 BMP-2 的 mRNA 也增加，而基质基因 COL2A1 和聚集蛋白聚糖的 mRNA 下调。趋化因子的一个子集在 IL-1 β 水平非常低时迅速增加。 IL-1β诱导的表型被TGF-β1部分逆转，但BMP-2不能逆转。在 IL-1 beta 存在的情况下，FGF-18 增加 ADAMTS-4、聚集蛋白聚糖、BMP-2、COL2A1、CCL3、CCL4、CCL20、CXCL1、CXCL3、CXCL6、IL-1 13、IL-6 和 IL-8 的表达，并减少 ADAMTS-5、MMP-13、CCL2 和 CCL8。计算分析显示，最上调的趋化因子很可能受到转录因子肌细胞增强子结合因子-3 (MEF-3)、CCAAT/增强子结合蛋白 (C/EBP) 和核因子-κ B (NF-κ B) 的调节。结论：IL-1 beta 对影响基质基因的人软骨细胞中的基因表达谱具有多种影响 以及趋化因子和细胞因子。 TGF-β1 具有拮抗 IL-1β 诱导的某些表型的能力。 (C) 2008 年国际骨关节炎研究协会。由爱思唯尔有限公司出版。保留所有权利。
Objective: To provide a more complete picture of the effect of interleukin-1 beta (IL-1 beta) on adult human articular chondrocyte gene expression, in contrast to the candidate gene approach.Design: Chondrocytes from human knee cartilage were cultured in medium containing IL-1 beta. Changes in gene expression were analyzed by microarray and reverse transcriptase-polymerase chain reaction analysis. The ability of transforming growth factor beta-1 (TGF-beta 1), fibroblast growth factor (FGF)-18, and bone morphogenetic protein 2 (BMP-2) to alter the effects of IL-1 beta was analyzed. Computational analysis of the promoter regions of differentially expressed genes for transcription factor binding motifs was performed.Results: IL-1 beta-treated human chondrocytes showed significant increases in the expression of granulocyte colony stimulating factor-3, endothelial leukocyte adhesion molecule 1 and leukemia inhibitory factor as well as for a large group of chemokines that include CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, CXCL8, CCL2, CCL3, CCL4, CCL5, CCL8, CCL20, CCL3L1, CX3CL1 and the cytokine IL-6. As expected, the mRNA for matrix metalloproteinase (MMP)-13 and BMP-2 also increased while mRNA for the matrix genes COL2A1 and aggrecan was down-regulated. A subset of chemokines increased rapidly at very low levels of IL-1 beta. The phenotype induced by IL-1 beta was partially reversed by TGF-beta 1, but not by BMP-2. In the presence of IL-1 beta, FGF-18 increased expression of ADAMTS-4, aggrecan, BMP-2, COL2A1, CCL3, CCL4, CCL20, CXCL1, CXCL3, CXCL6, IL-1 13, IL-6, and IL-8 and decreased ADAMTS-5, MMP-13, CCL2, and CCL8. Computational analysis revealed a high likelihood that the most up-regulated chemokines are regulated by the transcription factors myocyte enhancer binding factor-3 (MEF-3), CCAAT/enhancer binding protein (C/EBP) and nuclear factor-kappa B (NF-kappa B).Conclusion: IL-1 beta has a diverse effect on gene expression profile in human chondrocytes affecting matrix genes as well as chemokines and cytokines. TGF-beta 1 has the ability to antagonize some of the phenotype induced by IL-1 beta. (C) 2008 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.