Interleukin-2 modulates the responsiveness to angiotensin II in cultured vascular smooth muscle cells
Interleukin-2 modulates the responsiveness to angiotensin II in cultured vascular smooth muscle cells
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DOI：
10.1016/s0021-9150(97)00107-x
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发表时间：
1997-08-01
期刊：
影响因子：
5.3
通讯作者：
Ogihara, T
中科院分区：
文献类型：
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作者：
Nabata, T;Fukuo, K;Ogihara, T
用白细胞介素-2（IL-2）（一种T细胞衍生的细胞因子）预孵育可增强血管紧张素II（AII）诱导的血管平滑肌细胞（VSMC）胞内Ca 2+（[Ca 2 +]（i））的增加。IL-2本身不影响AII诱导的基础[Ca ~（2+）]（i）水平或[Ca ~（2+）]（i）增加的最大反应。此外，IL-2诱导的增强没有观察到细胞外Ca 2+的情况下，表明IL-2增强AII诱导的Ca 2+内流。IL-2还增强了由All诱导的DNA合成的刺激，尽管单独的IL-2不刺激DNA合成。Genistein是一种蛋白酪氨酸激酶抑制剂，可显著抑制IL-2诱导的AII诱导的Ca ~（2+）内流和DNA合成的增加。抗肝素结合表皮生长因子样生长因子（HB-EGF）的中和抗体部分抑制IL-1诱导的由All诱导的DNA合成增强。这些结果表明，自分泌KB-EGF是部分参与IL-2诱导的DNA合成增强的机制。另一方面，IL-2刺激糖胺聚糖（GAG）和前列环素的合成，并增强AII诱导的GAG和前列环素合成的刺激。因此，IL-2可能通过调节VSMC对AII的反应性，在动脉粥样硬化和血管疾病的发病机制中发挥重要作用。(C)1997 Elsevier Science爱尔兰有限公司
Preincubation with interleukin-2 (IL-2), a T cell-derived cytokine, enhanced the increase in intracellular Ca2+ ([Ca2+](i)) induced by angiotensin II (AII) in vascular smooth muscle cells (VSMC). IL-2 itself did not affect the basal [Ca2+](i) level or the maximal response of [Ca2+](i) increase induced by AII. Furthermore, IL-2-induced enhancement was not observed in the absence of extracellular Ca2+, suggesting that IL-2 enhances Ca2+ influx induced by AII. IL-2 also enhanced the stimulation of DNA synthesis induced by All, although IL-2 alone did not stimulate DNA synthesis. Genistein, an inhibitor of protein tyrosine kinases, significantly inhibited IL-2-induced enhancement of both Ca2+ influx and DNA synthesis induced by AII. A neutralizing antibody against heparin-binding epidermal growth factor-like growth factor (HB-EGF) partially inhibited IL-l-induced enhancement of DNA synthesis induced by All. These findings suggest that autocrine KB-EGF is partially involved in the mechanism of IL-2-induced enhancement of DNA synthesis. On the other hand IL-2 stimulated both glycosaminoglycan (GAG) and prostacyclin syntheses and enhanced the stimulation of both GAG and prostacyclin syntheses induced by AII. Therefore, IL-2 may play important roles in the pathogenesis of atherosclerosis and vascular disease by modulating the responsiveness to AII in VSMC. (C) 1997 Elsevier Science Ireland Ltd.