Urocortin-related peptides increase interleukin-6 output via cyclic adenosine 5'-monophosphate-dependent pathways in A7r5 aortic smooth muscle cells.
Urocortin-related peptides increase interleukin-6 output via cyclic adenosine 5'-monophosphate-dependent pathways in A7r5 aortic smooth muscle cells.
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DOI：
10.1210/en.2002-0023
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发表时间：
2003-06
期刊：
影响因子：
4.8
通讯作者：
K. Kageyama;T. Suda
中科院分区：
文献类型：
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作者：
K. Kageyama;T. Suda
促肾上腺皮质激素释放因子受体2型β在啮齿动物心血管系统中表达，是G蛋白偶联受体家族的一员。该受体与腺苷酸环化酶正偶联，并优先与尿皮质素（Ucn）相关肽（Uncs）结合：Ucn、Ucn II和Ucn III。在本研究中，我们研究了Ucns对A7r5主动脉平滑肌细胞中IL-6水平的影响。在该细胞系中，Ucn和Ucn II均通过促肾上腺皮质激素释放因子受体2型β诱导细胞内cAMP的积累，并引起IL-6输出水平的显著增加。腺苷酸环化酶抑制剂MDL-12330A抑制Ucn-或Ucn ii诱导的IL-6水平升高。虽然蛋白激酶a抑制剂H89 （10 nM）对IL-6浓度的增加没有影响，但发现蛋白激酶C抑制剂双吲哚酰马来酰亚胺I （10 nM）显著抑制IL-6的输出水平。p38 MAPK抑制剂SB203580 （100 nM）阻断Ucn-或Ucn ii诱导IL-6水平升高，表明p38 MAPK通路参与了这一调控。双吲哚马来酰亚胺I和SB203580协同抑制camp介导的IL-6水平升高。这些发现表明，蛋白激酶C和p38 MAPK信号级联都参与了A7r5主动脉平滑肌细胞中Ucns-cAMP通路的下游。
Corticotropin-releasing factor receptor type 2beta, expressed in the rodent cardiovascular system, is a member of the G protein-coupled receptor family. This receptor is coupled positively to adenylate cyclase and is bound preferentially by the urocortin (Ucn)-related peptides (Uncs): Ucn, Ucn II, and Ucn III. In the present study, we investigated the effects of Ucns on IL-6 levels in A7r5 aortic smooth muscle cells. In this cell line, both Ucn and Ucn II induced accumulation of intracellular cAMP via corticotropin-releasing factor receptor type 2beta and also caused a significant increase in IL-6 output levels. The adenylate cyclase inhibitor, MDL-12330A, inhibited this Ucn- or Ucn II-induced increase in IL-6 levels. Although H89 (10 micro M), a protein kinase A inhibitor, had no effect on the increase in IL-6 concentration, bisindolylmaleimide I (10 nM), a protein kinase C inhibitor, was found to significantly inhibit IL-6 output levels. Blockade of Ucn- or Ucn II-induced increases in IL-6 levels by SB203580 (100 nM), a p38 MAPK inhibitor, suggested that the p38 MAPK pathway was involved in this regulation. The cAMP-mediated increase in IL-6 levels was suppressed synergistically by both bisindolylmaleimide I and SB203580. These findings demonstrate that both protein kinase C and p38 MAPK signaling cascades are involved downstream of the Ucns-cAMP pathway in A7r5 aortic smooth muscle cells.