Bhat G J, Baker K M
Pen State University College of Medicine, Weis Center for Research, Danville, PA 17822, USA.
Basic Res Cardiol. 1998;93 Suppl 3:26-9. doi: 10.1007/s003950050203.
In cultured neonatal rat cardiac fibroblasts and CHO-K1 cells expressing angiotensin II (Ang II) type 1 receptors (AT1) (T3CHO/AT1A cell line), Ang II induced a delayed tyrosine phosphorylation of Stat3 (Signal Transducers and Activators of Transcription) with maximal activation at 2 h. This was in contrast to the rapid tyrosine phosphorylation (15-30 min) of Stat3 by the cytokine interleukin-6 (IL-6). Using T3CHO/AT1A cells, we tested the hypothesis that the delayed tyrosine phosphorylation of Stat3 by Ang II resulted from the induction of an inhibitory pathway (0-30 min) prior to activation (1-2 h). In support of this hypothesis, we observed that a short treatment of cells with Ang II transiently inhibited the IL-6-induced Stat3 tyrosine phosphorylation. The inhibitory effect of Ang II could be attenuated by exposing the cells to a specific inhibitor of MAP kinase kinase 1, PD98059. Such modulatory cross-talk between Ang II and IL-6 may have relevance in pathophysiological conditions such as cardiac hypertrophy, and in acute phase and inflammatory responses.
在培养的新生大鼠心脏成纤维细胞和表达血管紧张素II（Ang II）1型受体（AT1）的CHO-K1细胞（T3CHO/AT1A细胞系）中，Ang II诱导信号转导子和转录激活子3（Stat3）的酪氨酸磷酸化延迟，在2小时时激活达到最大值。这与细胞因子白细胞介素-6（IL-6）引起的Stat3快速酪氨酸磷酸化（15 - 30分钟）形成对比。利用T3CHO/AT1A细胞，我们检验了这样一个假说，即Ang II导致的Stat3酪氨酸磷酸化延迟是由于在激活（1 - 2小时）之前诱导了一条抑制性途径（0 - 30分钟）。为支持这一假说，我们观察到用Ang II短暂处理细胞会短暂抑制IL-6诱导的Stat3酪氨酸磷酸化。通过使细胞暴露于丝裂原活化蛋白激酶激酶1（MAPKK1）的特异性抑制剂PD98059，Ang II的抑制作用可以减弱。Ang II与IL-6之间这种调节性串扰可能与诸如心脏肥大以及急性期和炎症反应等病理生理状况相关。
