ANG II is involved in the LPS-induced production of proinflammatory cytokines in dehydrated rats
ANG II is involved in the LPS-induced production of proinflammatory cytokines in dehydrated rats
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DOI：
10.1152/ajpregu.00700.2002
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发表时间：
2003-04-01
影响因子：
2.8
通讯作者：
Watanabe, T
中科院分区：
文献类型：
--
作者：
Miyoshi, M;Nagata, K;Watanabe, T
我们之前报道的结果使我们推测Ang II参与了内毒素诱导的促炎细胞因子的产生，特别是在脱水条件下。为了验证这种可能性，在本研究中，我们检测了血管紧张素转换酶(ACE)抑制剂和1型Ang II受体(AT受体)拮抗剂对内毒素诱导的脱水大鼠前炎症细胞因子IL-1和IL-6产生的影响。单次静脉注射脂多糖可诱导大鼠肝脏IL-1βmRNA表达显著增加，该作用可被ACE抑制剂预处理后显著减弱。此外，血管紧张素转换酶抑制剂可降低内毒素引起的肝脏IL-1β蛋白浓度的升高。当内毒素注射前静脉注射AT(1)受体拮抗剂时，肝组织中IL-1β浓度升高的幅度明显减小。最后，血管紧张素转换酶抑制剂降低了内毒素引起的血浆IL-6浓度的升高。这些结果首次在体内证明Ang II及其AT(1)受体在内毒素在脱水条件下诱导的促炎细胞因子的产生中起重要作用。
We have previously reported results that led us to speculate that ANG II is involved in the LPS-induced production of proinflammatory cytokines, especially under dehydrated conditions. To test this possibility, in this study we examined the effects of an angiotensin-converting enzyme (ACE) inhibitor and an antagonist of the type-1 ANG II receptor (AT, receptor) on the LPS-induced production of the proinflammatory cytokines IL-1 and IL-6 in dehydrated rats. A single intravenous injection of LPS induced a marked increase in the expression of IL-1beta mRNA in the liver, an effect that was significantly attenuated by pretreatment with the ACE inhibitor. Furthermore, the ACE inhibitor reduced the LPS-induced increase in the hepatic concentration of IL-1beta protein. When the AT(1)-receptor antagonist was given intravenously before the LPS, the increase in the hepatic concentration of IL-1beta was significantly reduced. Finally, the ACE inhibitor reduced the LPS-induced increase in the plasma concentration of IL-6. These results represent the first in vivo evidence that ANG II and its AT(1) receptor play important roles in the production of proinflammatory cytokines that is induced by LPS under dehydrated conditions.