Early response genes induced in chondrocytes stimulated with the inflammatory cytokine interleukin-1beta.
Early response genes induced in chondrocytes stimulated with the inflammatory cytokine interleukin-1beta.
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DOI：
10.1186/ar331
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Brinckerhoff CE
中科院分区：
文献类型：
--
作者：
Vincenti MP;Brinckerhoff CE
最近的研究已经确定，IL-1β在类风湿性关节炎和骨关节炎中观察到的炎症和结缔组织破坏中起核心作用。这些过程是由这种炎性细胞因子激活中性蛋白酶（如基质金属蛋白酶）基因表达的能力引起的。虽然IL-1β在几小时内激活基质金属蛋白酶基因，但它也激活了即刻早期基因，这些基因是基质金属蛋白酶和其他关节炎持续基因后期表达所需的。为了鉴定参与IL-1β介导的关节炎疾病的推定的立即早期基因，用该细胞因子刺激软骨细胞系（SW 1353）2小时，分离总RNA，并通过微阵列分析鉴定表达的基因。该分析确定了多种转录因子、细胞因子、生长因子及其受体、粘附分子、蛋白酶和信号中间体表达的改变，这些可能导致关节炎中的炎症和软骨破坏。有趣的是，通过逆转录聚合酶链反应证实活化蛋白-1家族成员的表达揭示了junB（一种已知的c-jun的转录拮抗剂）的优先增加。没有观察到早期生长反应基因-1的诱导，通过逆转录聚合酶链反应检测到IL-1处理1小时基本上和短暂地诱导了早期生长反应基因-1，可以用早期诱导后已知的消息不稳定性来解释。然而，该分析已经鉴定了许多IL-1β应答基因，这些基因作为关节炎疾病的介质值得进一步研究。
Recent work has established that IL-1β plays a central role in the inflammation and connective tissue destruction observed in both rheumatoid arthritis and osteoarthritis. These processes result from the ability of this inflammatory cytokine to activate expression of genes for neutral proteases, such as the matrix metalloproteinases. While IL-1β activates matrix metalloproteinase genes within several hours, it also activates immediate early genes, which are required for the later expression of matrix metalloproteinases and other arthritis-perpetuating genes, are also activated. To identify putative immediate early genes involved in IL-1β-mediated arthritic disease, a chondrocytic cell line (SW1353) was stimulated with this cytokine for 2 hours, total RNA was isolated, and expressed genes were identified by microarray analysis. This analysis identified alterations in the expression of multiple transcription factors, cytokines, growth factors and their receptors, adhesion molecules, proteases, and signaling intermediates that may contribute to inflammation and cartilage destruction in arthritis. Interestingly, confirmation of the expression of activating protein-1 family members by reverse transcriptase polymerase chain reaction revealed a preferential increase in junB, a known transcriptional antagonist of c-jun. The failure to observe induction of early growth response gene-1, which was detected by reverse transcriptase polymerase chain reaction to be substantially and transiently induced by 1 hour of IL-1 treatment, may be explained by the known instability of the message after early induction. However, this analysis has identified numerous IL-1β-responsive genes that warrant further investigation as mediators of disease in arthritis.
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