Candesartan reduces the innate immune response to lipopolysaccharide in human monocytes.
Candesartan reduces the innate immune response to lipopolysaccharide in human monocytes.
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DOI：
10.1097/hjh.0b013e3283314bc7
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发表时间：
2009-12
影响因子：
4.9
通讯作者：
Saavedra JM
中科院分区：
文献类型：
--
作者：
Larrayoz IM;Pang T;Benicky J;Pavel J;Sánchez-Lemus E;Saavedra JM
抑制血管紧张素II受体1（AT 1）可减少与高血压相关的慢性炎症。我们询问AT 1受体抑制是否会减少细菌脂多糖（LPS）诱导的先天性炎症反应。我们使用未经刺激的人循环单核细胞从健康供体逆流离心淘析。单核细胞在体外与LPS（50 ng/ml）孵育后进行了研究，其中含有和不含1 μmol/l坎地沙坦（一种AT 1受体阻断剂）。血管紧张素II受体mRNA的表达通过逆转录酶-PCR和受体结合放射自显影法测定;炎症因子mRNA的表达通过逆转录酶-PCR和细胞因子释放ELISA法进行研究。人单核细胞不表达可检测的AT 1受体，血管紧张素II不诱导炎症因子mRNA表达或细胞因子释放。然而，坎地沙坦显著降低LPS诱导的LPS识别蛋白分化簇14、促炎细胞因子肿瘤坏死因子α、白细胞介素-1 β和白细胞介素-6以及凝集素样氧化低密度脂蛋白受体的mRNA表达。此外，坎地沙坦降低核因子κ B途径的激活、肿瘤坏死因子α和白细胞介素6的分泌以及LPS诱导的ROS形成，而不影响白细胞介素10的分泌。我们推测坎地沙坦在这些细胞中的抗炎作用可能是由与AT 1受体阻断无关的机制介导的。我们的研究结果表明，坎地沙坦显着降低人循环单核细胞对LPS的先天性免疫反应。坎地沙坦的抗炎作用可能不仅在高血压中而且在其他炎性疾病中具有重要意义。
Inhibition of angiotensin II receptor type 1 (AT1) reduces chronic inflammation associated with hypertension. We asked whether AT1 receptor inhibition would reduce the innate inflammatory response induced by bacterial lipopolysaccharide (LPS). We used unstimulated human circulating monocytes obtained from healthy donors by counterflow centrifugal elutriation. Monocytes were studied in vitro after incubation with LPS (50 ng/ml) with and without 1 μmol/l candesartan, an AT1 receptor blocker. Angiotensin II receptor mRNA expression was determined by reverse transcriptase-PCR and receptor binding by autoradiography; inflammatory factor mRNA expression was studied by reverse transcriptase-PCR and cytokine release by ELISA. Human monocytes did not express detectable AT1 receptors, and angiotensin II did not induce inflammatory factor mRNA expression or cytokine release. However, candesartan substantially reduced the LPS-induced expression of the mRNAs for the LPS recognition protein cluster of differentiation 14, the proinflammatory cytokines tumor necrosis factor alpha, interleukin-1 beta and interleukin-6 and the lectin-like oxidized low-density lipoprotein receptor. In addition, candesartan reduced the activation of the nuclear factor kappa B pathway, the tumor necrosis factor alpha and interleukin-6 secretion, and the ROS formation induced by LPS, without affecting the secretion of interleukin-10. We hypothesize that the anti-inflammatory effects of candesartan in these cells are likely mediated by mechanisms unrelated to AT1 receptor blockade. Our results demonstrate that candesartan significantly reduces the innate immune response to LPS in human circulating monocytes. The anti-inflammatory effects of candesartan may be of importance not only in hypertension but also in other inflammatory disorders.