The aldosterone-mineralocorticoid receptor pathway exerts anti-inflammatory effects in endotoxin-induced uveitis.
The aldosterone-mineralocorticoid receptor pathway exerts anti-inflammatory effects in endotoxin-induced uveitis.
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DOI：
10.1371/journal.pone.0049036
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Behar-Cohen F
中科院分区：
文献类型：
--
作者：
Bousquet E;Zhao M;Ly A;Leroux Les Jardins G;Goldenberg B;Naud MC;Jonet L;Besson-Lescure B;Jaisser F;Farman N;De Kozak Y;Behar-Cohen F
我们之前已经证明眼睛是盐皮质激素敏感的器官，现在我们质疑盐皮质激素受体（MR）在眼部炎症中的作用。内毒素诱导的葡萄膜炎（EIU）是一种人眼内炎症的大鼠模型，是通过全身施用脂多糖（LPS）诱导的。眼内注射醛固酮（与LPS注射同时）后6小时和24小时进行评价。 EIU发病后3小时，虹膜/睫状体中MR和糖皮质激素代谢酶11-β羟基类固醇脱氢酶2型（11β-HSD2）表达下调，房水中皮质酮浓度升高，改变了正常的MR/糖皮质激素受体（GR）平衡。 24小时时，GR表达也下降。在 EIU 中，醛固酮以剂量依赖性方式降低临床炎症的强度。醛固酮的临床益处在 MR 拮抗剂 (RU26752) 存在时被消除，而 GR 拮抗剂 (RU38486) 则仅部分消除。醛固酮减少房水中炎症介质（6 小时和 24 小时：TNF-α、IFN-γ、MIP-1α）的释放以及活化的小胶质细胞/巨噬细胞的数量。醛固酮部分阻止了葡萄膜炎引起的 MR 下调。这些结果表明，虹膜/睫状体中的 MR 表达和激活可以保护眼部结构免受 EIU 引起的损伤。
We have previously shown that the eye is a mineralocorticoid-sensitive organ and we now question the role of mineralocorticoid receptor (MR) in ocular inflammation. The endotoxin-induced uveitis (EIU), a rat model of human intraocular inflammation, was induced by systemic administration of lipopolysaccharide (LPS). Evaluations were made 6 and 24 hours after intraocular injection of aldosterone (simultaneous to LPS injection). Three hours after onset of EIU, the MR and the glucocorticoid metabolizing enzyme 11-beta hydroxysteroid dehydrogenase type 2 (11β-HSD2) expression were down-regulated in iris/ciliary body and the corticosterone concentration was increased in aqueous humor, altering the normal MR/glucocorticoid receptor (GR) balance. At 24 hours, the GR expression was also decreased. In EIU, aldosterone reduced the intensity of clinical inflammation in a dose-dependent manner. The clinical benefit of aldosterone was abrogated in the presence of the MR antagonist (RU26752) and only partially with the GR antagonist (RU38486). Aldosterone reduced the release of inflammatory mediators (6 and 24 hours: TNF-α, IFN-γ, MIP-1α) in aqueous humor and the number of activated microglia/macrophages. Aldosterone partly prevented the uveitis-induced MR down-regulation. These results suggest that MR expression and activation in iris/ciliary body could protect the ocular structures against damages induced by EIU.
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影响因子：
8.8
作者：
Hicks, Caitlin W.;Sweeney, Daniel A.;Natanson, Charles
通讯作者：
Natanson, Charles
影响因子：
4.8
作者：
Deuchar GA;McLean D;Hadoke PWF;Brownstein DG;Webb DJ;Mullins JJ;Chapman K;Seckl JR;Kotelevtsev YV
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8.3
作者：
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通讯作者：
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37.8
作者：
Michel, F;Ambroisine, ML;Silvestre, JS
通讯作者：
Silvestre, JS