Increase in chemokine CXCL1 by ERβ ligand treatment is a key mediator in promoting axon myelination.
Increase in chemokine CXCL1 by ERβ ligand treatment is a key mediator in promoting axon myelination.
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DOI：
10.1073/pnas.1721732115
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发表时间：
2018-06-12
影响因子：
11.1
通讯作者：
Tiwari-Woodruff SK
中科院分区：
文献类型：
--
作者：
Karim H;Kim SH;Lapato AS;Yasui N;Katzenellenbogen JA;Tiwari-Woodruff SK
CXCL 1是一种主要的中性粒细胞趋化因子，它与中性粒细胞和少突胶质细胞上的趋化因子受体CXCR 2结合。雌激素受体β配体治疗多发性硬化小鼠模型诱导外周和脑CXCL 1水平增加，这与轴突髓鞘再生增加相关。CXCL 1引起的少突胶质细胞祖细胞的募集和分化，与减少细胞凋亡的减弱的IFN-γ产生相结合，可能是雌激素受体β配体发挥其临床益处的至少一种途径。雌激素受体β（ERβ）配体促进多发性硬化小鼠模型的髓鞘再生。最近的工作使用实验性自身免疫性脑脊髓炎（EAE）表明，ERβ配体诱导轴突髓鞘再生，但不同程度地影响外周炎症。为了鉴定ERβ配体是否在髓鞘再生中启动共同的免疫机制，评估了在EAE峰值时给予ERβ配体的小鼠的中枢和外周免疫和病理学。所有ERβ配体诱导细胞因子和趋化因子的差异表达，但增加外周和星形胶质细胞中CXCL 1的水平。少突胶质细胞CXCR 2结合CXCL 1，并参与正常的髓鞘形成。此外，尽管免疫细胞在CNS中大量蓄积，但所有ERβ配体在EAE高峰时均促进小鼠广泛的髓鞘再生。这一发现强调了ERβ配体介导髓鞘再生机制的一个组成部分。因此，免疫系统和中枢神经系统之间的相互作用可能是ERβ配体的髓鞘再生作用的原因。我们发现CXCL 1的存在可能产生潜在的神经保护作用，这可能对改善多发性硬化症的治疗方法有意义。
CXCL1 is a major neutrophil chemoattractant that binds to the chemokine receptor, CXCR2, on neutrophils and oligodendrocytes. Estrogen receptor β ligand treatment in a mouse model of multiple sclerosis induces an increase in peripheral and brain CXCL1 levels that correlate with an increase in axon remyelination. Oligodendrocyte progenitor recruitment and differentiation by CXCL1, in combination with attenuated IFN-γ production reducing apoptosis, may account for at least one avenue whereby estrogen receptor β ligands exert their clinical benefits. Estrogen receptor β (ERβ) ligands promote remyelination in mouse models of multiple sclerosis. Recent work using experimental autoimmune encephalomyelitis (EAE) has shown that ERβ ligands induce axon remyelination, but impact peripheral inflammation to varying degrees. To identify if ERβ ligands initiate a common immune mechanism in remyelination, central and peripheral immunity and pathology in mice given ERβ ligands at peak EAE were assessed. All ERβ ligands induced differential expression of cytokines and chemokines, but increased levels of CXCL1 in the periphery and in astrocytes. Oligodendrocyte CXCR2 binds CXCL1 and has been implicated in normal myelination. In addition, despite extensive immune cell accumulation in the CNS, all ERβ ligands promoted extensive remyelination in mice at peak EAE. This finding highlights a component of the mechanism by which ERβ ligands mediate remyelination. Hence, interplay between the immune system and central nervous system may be responsible for the remyelinating effects of ERβ ligands. Our findings of potential neuroprotective benefits arising from the presence of CXCL1 could have implications for improved therapies for multiple sclerosis.
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DOI：
10.1111/aji.12021
发表时间：
2013-02
期刊：
American journal of reproductive immunology (New York, N.Y. : 1989)
影响因子：
--
作者：
Hickey DK;Fahey JV;Wira CR
通讯作者：
Wira CR
影响因子：
6.1
作者：
Kumar S;Patel R;Moore S;Crawford DK;Suwanna N;Mangiardi M;Tiwari-Woodruff SK
通讯作者：
Tiwari-Woodruff SK
影响因子：
6.2
作者：
Filipovic, Radmiia;Zecevic, Nada
通讯作者：
Zecevic, Nada
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.
DOI：
10.1073/pnas.1411294111
发表时间：
2014-12-16
影响因子：
11.1
作者：
Moore, Spencer M.;Khalaj, Anna J.;Tiwari-Woodruff, Seema Kaushalya
通讯作者：
Tiwari-Woodruff, Seema Kaushalya