Post-transcriptional and nongenomic effects of glucocorticoids.
Post-transcriptional and nongenomic effects of glucocorticoids.
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DOI：
10.1513/pats.200402-015ms
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发表时间：
2004-01-01
期刊：
影响因子：
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通讯作者：
Stellato, Cristiana
中科院分区：
文献类型：
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作者：
Stellato, Cristiana
糖皮质激素干扰转录后基因调控的能力最近被认为是其抗炎特性的潜在重要组成部分，控制这种活性的机制正在积极研究中。一些研究表明，糖皮质激素可以抑制已知的控制mRNA周转和翻译的炎症信号通路。此外，在炎症基因的mRNA分子上已经发现了几个糖皮质激素敏感的决定因素，与它们相互作用的rna结合因子可能构成相关的糖皮质激素靶点。糖皮质激素也发挥非基因组效应，在给药后几分钟内发生。非基因组糖皮质激素作用的机制不同于经典的转录依赖的糖皮质激素作用，涉及第二信使分子的产生和信号转导途径的激活，可能是通过核糖皮质激素受体或膜糖皮质激素受体，但尚未完全表征。最终，糖皮质激素介导作用的新途径的发现应该会改善抗炎治疗的靶点。
The ability of glucocorticoids to interfere with post-transcriptional gene regulation has recently been recognized as a potentially important part of their anti-inflammatory property, and the mechanisms governing such activity are under active investigation. Several studies have shown that glucocorticoids can inhibit inflammatory signaling pathways known to control mRNA turnover and translation. Moreover, several glucocorticoid-sensitive determinants have been identified on mRNA molecules of inflammatory genes, and the RNA-binding factors interacting with them might constitute relevant glucocorticoid targets. Glucocorticoids also exert effects characterized as nongenomic, which occur within minutes of drug administration. The mechanisms of action of nongenomic glucocorticoid effects differ from the classical, transcription-dependent glucocorticoid action and involve the production of second-messenger molecules and activation of signal transduction pathways, either by the nuclear glucocorticoid receptor or by a membrane glucocorticoid receptor that has not yet been fully characterized. Ultimately, the discovery of novel pathways involved in mediating the actions of glucocorticoids should lead to improved targets for anti-inflammatory therapy.