Beneficial role of the GPR30 agonist G-1 in an animal model of multiple sclerosis.
Beneficial role of the GPR30 agonist G-1 in an animal model of multiple sclerosis.
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DOI：
10.1016/j.jneuroim.2009.06.023
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发表时间：
2009-09-29
影响因子：
3.3
通讯作者：
Horuk R
中科院分区：
文献类型：
--
作者：
Blasko E;Haskell CA;Leung S;Gualtieri G;Halks-Miller M;Mahmoudi M;Dennis MK;Prossnitz ER;Karpus WJ;Horuk R
The beneficial effects of estrogens in multiple sclerosis are thought to be mediated exclusively by the classical nuclear estrogen receptors ERα and ERβ. However, recently many reports revealed that estrogens are able to mediate rapid signals through a G protein-coupled receptor (GPCR), known as GPR30. In the present study, we set out to explore whether effects mediated through this receptor were anti-inflammatory and could account for some of the beneficial effects of estrogen. We demonstrate that GPR30 is expressed in both human and mouse immune cells. Furthermore a GPR30-selective agonist, G-1, previously described by us, inhibits the production of lipopolysaccharide (LPS)-induced cytokines such as TNF-α and IL-6 in a dose-dependent manner in human primary macrophages and in a murine macrophage cell line. These effects are likely mediated solely through the estrogen-specific receptor GPR30 since the agonist G-1 displayed an IC50 far greater than 10 μM on the classical nuclear estrogen receptors as well as a panel of 25 other GPCRs. Finally, we show that the agonist G-1 is able to reduce the severity of disease in both active and passive EAE models of multiple sclerosis in SJL mice and that this effect is concomitant with a G-1-mediated decrease in proinflammatory cytokines, including IFN-γ and IL-17, in immune cells harvested from these mice. The effect of G-1 appears indirect, as the GPR30 agonist did not directly influence IFN-γ or IL-17 production by purified T cells. These data indicate that G-1 may represent a novel therapeutic agent for the treatment of chronic autoimmune, inflammatory diseases.
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影响因子：
4.8
作者：
Guo, ZY;Krücken, J;Wunderlich, F
通讯作者：
Wunderlich, F
影响因子：
5.3
作者：
Morales, Laurie Beth J.;Loo, Kyi Kyi;Voskuhl, Rhonda R.
通讯作者：
Voskuhl, Rhonda R.
影响因子：
3.5
作者：
Kvingedal, AM;Smeland, EB
通讯作者：
Smeland, EB
影响因子：
3.3
作者：
Kennedy, KJ;Strieter, RM;Karpus, WJ
通讯作者：
Karpus, WJ
17β-雌二醇抑制实验性自身免疫性脑脊髓炎雌性小鼠中枢神经系统中细胞因子、趋化因子和趋化因子受体 mRNA 的表达
影响因子：
4.2
作者：
Matejuk, A;Adlard, K;Offner, H
通讯作者：
Offner, H