Dexamethasone, but not IL-1 alone, upregulates acute-phase serum amyloid A gene expression and production by cultured human aortic smooth muscle cells
Dexamethasone, but not IL-1 alone, upregulates acute-phase serum amyloid A gene expression and production by cultured human aortic smooth muscle cells
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DOI：
10.1046/j.1365-3083.2001.00829.x
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发表时间：
2001-01-01
影响因子：
3.7
通讯作者：
Sipe, JD
中科院分区：
文献类型：
--
作者：
Kumon, Y;Suehiro, T;Sipe, JD
虽然SAA 1和SAA 2蛋白亚型（A-SAA）的血清淀粉样蛋白A（SAA）家族的急性期反应物已被发现在一些肝外组织，合成的肝外SAA的网站仍有待澄清。为研究SAA蛋白在动脉粥样硬化斑块中的合成位点，本实验检测了培养的人主动脉平滑肌细胞（HASMC）中SAA 1和SAA 2基因的表达，并通过免疫印迹分析检测到A-SAA蛋白的亚型。A-SAA和C-SAA（SAA 4）mRNA亚型组成型表达的HASMC，但没有，然而，由人脐静脉内皮细胞。A-SAA mRNA的表达由HASMC上调皮质激素包括地塞米松（Dex），皮质酮，氢化可的松，和醛固酮，但不是由细胞因子白细胞介素（IL）-1，IL-6，和肿瘤坏死因子（TNF）-α单独。地塞米松对A-SAA mRNA的刺激在6 ~ 48 h呈时间和剂量依赖性。Dex上调HASMC中A-SAA mRNA的阈值浓度在0.1和1 nM之间。已知在其它细胞系统中上调肝外A-SAA基因表达的IL-1即使上调，也仅轻微上调HASMC的Dex诱导的A-SAA表达。因此，血管壁（动脉粥样硬化斑块）中的一些A-SAA蛋白可能来源于平滑肌细胞。考虑到A-SAA调节炎症过程和脂质合成的最近报道，A-SAA可以潜在地用作平滑肌细胞内稳态的生理调节剂，在疾病状态下，参与动脉粥样硬化斑块的形成。
Although the SAA1 and SAA2 protein isoforms (A-SAA) of the serum amyloid A (SAA) family of acute phase reactants have been found in a number of extrahepatic tissues; the site of synthesis of extrahepatic SAA remains to be clarified. To investigate site(s) of synthesis of the SAA protein localized to atherosclerotic plaque, expression of the SAA1 and SAA2 genes by cultured human aortic smooth muscle cells (HASMC) was investigated, A-SAA protein isoforms were detectable by immunoblot analysis in the culture medium of HASMC. Both A-SAA and C-SAA (SAA4) mRNA isoforms were constitutively expressed by HASMC, but not, however, by the human umbilical vein endothelial cells. Expression of A-SAA mRNA by HASMC was upregulated by corticoid hormones including dexamethasone (Dex), corticosterone, hydrocortisone, and aldosterone, but not by the cytokines interleukin (IL)-1, IL-6, and tumour necrosis factor (TNF)-alpha alone. Dex stimulation of A-SAA mRNA was time and dose dependent from 6 to 48 h. The threshold concentration for upregulation of A-SAA mRNA in HASMC by Dex was between 0.1 and 1 nM. IL-1, known to upregulate extrahepatic A-SAA gene expression in other cell systems only slightly, if at all, upregulated Dex-induced A-SAA expression by HASMC. Thus, it is possible that some of the A-SAA protein in the vascular wall (atherosclerotic plaques) can originate from smooth muscle cells. In consideration of recent reports that A-SAA modulates the inflammatory process and lipid synthesis, A-SAA can potentially serve as a physiological regulator of smooth muscle cell homeostasis within that, in a disease state, participates in the formation of atherosclerotic plaques.