首页> 外文期刊>Rheumatology >Mechanism of the anti-inflammatory effect of colchicine in rheumatic diseases: a possible new outlook through microarray analysis.
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Mechanism of the anti-inflammatory effect of colchicine in rheumatic diseases: a possible new outlook through microarray analysis.

机译:秋水仙碱在风湿性疾病中的抗炎作用机理:通过微阵列分析的可能新观点。

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OBJECTIVE: Colchicine is an alkaloid that is used to alleviate acute gout and to prevent acute attacks of familial Mediterranean fever (FMF). However, it is not beneficial when given during the occurrence of an acute episode of FMF. It is believed that colchicine exerts its anti-inflammatory effect through direct interaction with microtubules. We aim to study the molecular basis of colchicine action by analysing the effect of this drug on global gene expression of HUVEC (human umbilical vein endothelial cell line) cells. METHODS: HUVEC cells were exposed to various concentrations of colchicine and were harvested at different time points. Ribonucleic acid was extracted, amplified, reverse transcribed and hybridized to complementary deoxyribonucleic acid microarrrays containing more than 40,000 probes to human expressed sequence tags. This approach enabled us to have a global look at the transcriptional response induced by colchicine treatment. RESULTS: Colchicine changed the expression of many genes in HUVEC cells following exposure to a concentration of 100 ng/ml or higher. Following short exposure (30 or 120 min), colchicine affected genes known to be involved in the cell cycle and its regulation. However, change in expression of genes involved in neutrophil migration or other inflammatory processes were observed mainly after 12 to 24 h. CONCLUSIONS: The anti-inflammatory effect of colchicine may be mediated not only through direct interaction with microtubules but also through changes at the transcriptional level. This latter effect apparently requires a higher concentration and a longer time to occur. This can explain the observation that colchicine does not have an immediate effect when given during an acute attack of FMF.
机译:目的:秋水仙碱是一种生物碱,用于缓解急性痛风和预防家族性地中海热(FMF)的急性发作。但是,如果在FMF急性发作期间给予,则无益。据信秋水仙碱通过与微管直接相互作用而发挥其抗炎作用。我们旨在通过分析该药物对HUVEC(人脐静脉内皮细胞系)细胞整体基因表达的作用来研究秋水仙碱作用的分子基础。方法:HUVEC细胞暴露于不同浓度的秋水仙碱中,并在不同的时间点收获。提取核糖核酸,进行扩增,反转录并与互补的脱氧核糖核酸微阵列杂交,该微阵列包含超过40,000种针对人类表达的序列标签的探针。这种方法使我们能够全面了解秋水仙碱处理诱导的转录反应。结果:秋水仙碱暴露于浓度为100 ng / ml或更高的HUVEC细胞后改变了许多基因的表达。短暂暴露(30或120分钟)后,秋水仙碱影响的基因已知参与细胞周期及其调控。然而,主要在12至24小时后观察到涉及中性粒细胞迁移或其他炎症过程的基因表达变化。结论秋水仙碱的抗炎作用不仅可以通过与微管的直接相互作用来介导,还可以通过转录水平的改变来介导。后一种效果显然需要更高的浓度和更长的时间才能发生。这可以解释观察到的事实,即在FMF的急性发作期间给予秋水仙碱不会立即起效。

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