Autocrine/paracrine secretion of IL-6 family cytokines causes angiotensin II-induced delayed STAT3 activation
Autocrine/paracrine secretion of IL-6 family cytokines causes angiotensin II-induced delayed STAT3 activation
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DOI：
10.1006/bbrc.2000.2364
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发表时间：
2000-03-24
影响因子：
3.1
通讯作者：
Ogawa, S
中科院分区：
文献类型：
--
作者：
Sano, M;Fukuda, K;Ogawa, S
我们最近报道，血管紧张素II(AngII)在心肌细胞的晚期(120min)双相激活JAK/STAT通路并诱导STATs的延迟磷酸化。本研究旨在探讨STAT3的延迟磷酸化机制。经血管紧张素转换酶刺激的心肌细胞制备的条件培养液在5min时可重现STAT3的酪氨酸磷酸化。这种延迟的磷酸化几乎完全被抗gp130阻断抗体RX435所抑制，但不能被TAK044(ET-A/B-R拮抗剂)、哌唑嗪或心得安所抑制。晚期AngII诱导gp130的磷酸化，与STAT3的延迟磷酸化在时间上是平行的。在30~60min时，Angii促进IL-6、CT-1和LIF的表达，但不增加CNTF的表达；在2 h时，Angii使条件培养液中IL-6蛋白水平增加3倍。这些结果表明，血管紧张素Ⅱ诱导的STAT3延迟激活是由自分泌/旁分泌分泌的IL-6家族细胞因子引起的。(C)2000年学术出版社。
We recently reported that angiotensin II (AngII) biphasically activates the JAK/STAT pathway and induces delayed phosphorylation of STATS in the late stage (120 min) in cardiomyocytes. This study was designed to determine the mechanism of delayed phosphorylation of STAT3. Conditioned medium prepared from AngII-stimulated cardiomyocytes could reproduce the tyrosine phosphorylation of STAT3 at 5 min. This delayed phosphorylation was almost completely inhibited by anti-gp130 blocking antibody RX435, but not by TAK044 (ET-A/B-R antagonist), prazosin, or propranolol. AngII induced phosphorylation of gp130 in the late stage, which was temporally in parallel with the delayed phosphorylation of STAT3. AngII augmented IL-6, CT-1, and LIF mRNA expression at 30-60 min, but not CNTF expression, AngII increased IL-6 protein levels by 3-fold in the conditioned media at 2 h compared with the control. These findings indicated that AngII-induced delayed activation of STAT3 is caused by autocrine/paracrine secreted IL-6 family cytokines. (C) 2000 Academic Press.