Expression of Eph receptors and their ligands, ephrins, during lipopolysaccharide fever in rats
Expression of Eph receptors and their ligands, ephrins, during lipopolysaccharide fever in rats
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DOI：
10.1152/physiolgenomics.00043.2004
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发表时间：
2005-04-14
影响因子：
4.6
通讯作者：
Romanovsky, AA
中科院分区：
文献类型：
--
作者：
Ivanov, AI;Steiner, AA;Romanovsky, AA
促红细胞生成素(EPH)受体酪氨酸激酶及其配体通过介导细胞黏附和迁移参与胚胎发育和肿瘤发生。虽然细菌脂多糖在体外可以诱导肾上腺素，但它们在体内是否参与炎症反应尚不清楚。通过差异显示，我们发现发热性剂量的内毒素(50ug/kg iv)可诱导大鼠肝脏中eaffin-A1的转录上调。我们通过实时荧光RT-PCR证实了这一发现。然后，我们对不同器官中不同肾上腺素和Eph受体在不同器官中的表达进行了定量。发热期2(脂多糖后90min)和发热期3(300min)的特征是几种肾上腺素和Eph受体的强烈上调(高达16倍)和下调(高达21倍)。除EphA2外，EphA2的表达变化仅限于肝脏和肺这两个内毒素处理器官，EphA2在脑组织中的表达在第2时相上调。EphA_2和EphA_2在肝脏和肺中表达下调，EphB_3下调，EphA_2在肝脏中表达上调，EphA_3和EphA_3在肝脏中表达上调，EphA_1和EphA_3在肝脏中表达上调，EphA_2和EphB_3在肝组织中表达上调。在肝脏中，EphA2和EphB_3在蛋白质水平上发生了转录变化。这些协调的、时相特异的反应表明，不同的肾上腺素和Eph受体可能参与了内毒素全身炎症反应的不同阶段的细胞事件(如组织屏障的破坏和白细胞的迁移)。
Erythropoietin-producing hepatocellular (Eph) receptor tyrosine kinases and their ligands, ephrins, are involved in embryogenesis and oncogenesis by mediating cell adhesion and migration. Although ephrins can be induced by bacterial LPS in vitro, whether they are involved in inflammation in vivo is unknown. Using differential mRNA display, we found that a febrigenic dose of LPS (50 mu g/kg iv) induces a strong transcriptional upregulation of ephrin-A1 in rat liver. We confirmed this finding by real-time RT-PCR. We then quantified the mRNA expression of different ephrins and Eph receptors at phases 1-3 of LPS fever in different organs. Febrile phases 2 (90 min post-LPS) and 3 (300 min) were characterized by robust upregulation (up to 16-fold) and downregulation (up to 21-fold) of several ephrins and Eph receptors. With the exception of EphA2, which showed upregulation in the brain at phase 2, expressional changes of Eph receptors and ephrins were limited to the LPS-processing organs: liver and lung. Characteristic, counter-directed changes in expressional regulation of Eph receptors and their corresponding ligands were found: upregulation of EphA2, downregulation of ephrin-A1 in the liver and lung at phase 2; downregulation of EphB3, upregulation of ephrin-B2 in the liver at phase 2; downregulation of EphA1 and EphA3, upregulation of ephrins-A1 and -A3 in liver at phase 3. In the liver, transcriptional changes of EphA2 and EphB3 at phase 2 were confirmed at protein level. These coordinated, phase-specific responses suggest that different sets of ephrins and Eph receptors may be involved in cellular events ( such as disruption of tissue barriers and leukocyte transmigration) underlying different stages of systemic inflammatory response to LPS.