Title of project : Mechanisms underlying angiotensin II-stimulated production of proinflammatory cytokines : Are transcription factors involved?

我们最近报道血管紧张素II(Ang II)和血管紧张素1型(AT1)受体参与了内毒素(LPS)诱导的大鼠肝、脾和脑组织中IL-1SS的表达。我们研究了血管紧张素Ⅱ是否通过影响脂多糖诱导的大鼠肝和脾中促炎症转录因子--核因子-κB和AP-1的激活来促进IL-1的产生。令人惊讶的是，脂多糖诱导肝组织中核因子-血管紧张素转换酶B的活化显著增加，这种作用被血管紧张素转换酶抑制剂和κ受体拮抗剂预先处理后显著增强(而不是减弱)。此外，AT1受体拮抗剂可显著增强内毒素诱导的脾组织AP-1的表达。提示内源性血管紧张素转换酶II或AT1受体抑制内毒素诱导的大鼠肝、脾转录因子的激活。我们的结果似乎不支持NF-κB和AP-1在血管紧张素II促进内毒素诱导的大鼠促炎细胞因子产生中起关键作用的观点。

We recently reported an involvement of angiotensin II(ANG II) and ANG type 1(AT1) receptor in the hepatic, splenic and brain expression of IL-1ss induced in rats by lipopolysaccharide(LPS). We investigated whether ANG II contributes to the IL-1 production through its effect on the activation of proinflammatory transcription factors, NF-κB and AP-1, induced in the rat's liver and spleen by LPS. Surprisingly, LPS induced a marked increase in the hepatic activation of NF-κB, an effect that was significantly enhanced (rather than reduced) by pre-treatment with the ACE inhibitor and AT1-receptor antagonist. Furthermore, the LPS-induced expression of splenic AP-1 was significantly augmented by pre-treatment with the AT1-receptor antagonist. The present results suggest that endogenous ANG II or AT1 receptor suppress the activation of the hepatic or splenic transcription factors in LPS-treated rats. Our results does not seem to support the idea that NF-κB and AP-1 play a key role in the ANG II-enhanced production of proinflammatory cytokines induced by LPS in rats.