Beneficial role of the GPR30 agonist G-1

decloud2009

以后求助文献请到论坛发帖，具体要求请看版规，也要支持论坛啊。
/ D* N* {2 h, I- R
# k3 }1 r: C+ |6 kThe beneficial effects of estrogens in multiple sclerosis are thought to be mediated exclusively by the classical
  K5 p) k9 b/ O. D% F1 ^nuclear estrogen receptors ERα and ERβ. However, recently many reports revealed that estrogens are able to1 i, [+ a8 ?' W% u0 H7 x
mediate rapid signals through a G protein-coupled receptor (GPCR), known as GPR30. In the present study,we
1 W3 z7 K: g+ Y# Oset out to explore whether effects mediated through this receptor were anti-inflammatory and could account6 l1 t5 V  a: p
for some of the beneficial effects of estrogen. We demonstrate that GPR30 is expressed in both human and( [" {5 P$ i3 V% @7 j
mouse immune cells. Furthermore a GPR30-selective agonist, G-1, previously described by us, inhibits the
0 |) m2 X* F/ o$ ~7 Qproduction of lipopolysaccharide (LPS)-induced cytokines such as TNF-αand IL-6 in a dose-dependentmanner
' i( s. c3 H1 z. Z' t+ X! B/ `6 a% i$ ~in human primary macrophages and in amurine macrophage cell line. These effects are likelymediated solely; c3 g  j0 a% T7 z8 I' M: v
through the estrogen-specific receptor GPR30 since the agonist G-1 displayed an IC50 far greater than 10 μMon% W. K+ j% T- F6 ~2 _/ ?
the classical nuclear estrogen receptors aswell as a panel of 25 other GPCRs. Finally,we showthat the agonistG-
7 a- Y' m0 g( Y9 N- b6 e: P: x1 is able to reduce the severity of disease in both active and passive EAEmodels ofmultiple sclerosis in SJLmice1 a3 U+ A# j; e# ^1 `( J) I
and that this effect is concomitant with a G-1-mediated decrease in proinflammatory cytokines, including IFN-# w, w. r! l, L. ]
γ and IL-17, in immune cells harvested fromthesemice. The effect of G-1 appears indirect, as the GPR30 agonist
; [5 L; Y6 ~) x0 S  L- Z/ \did not directly influence IFN-γ or IL-17 production by purified T cells. These data indicate that G-1 may
2 {) y( j$ {6 o3 Xrepresent a novel therapeutic agent for the treatment of chronic autoimmune, inflammatory diseases.

decloud2009

文章。

songxinxing

十分感谢～衷心的～谢谢decloud姐姐～