Immunoregulation of a CB2 receptor agonist in a murine model of neuroAIDS.

Immunoregulation of a CB2 receptor agonist in a murine model of neuroAIDS.
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DOI:
10.1007/s11481-010-9225-8
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发表时间:
2010-09
影响因子:
6.2
通讯作者:
Poluektova, Larisa
Poluektova, Larisa
中科院分区:
医学3区
文献类型:
--
作者:
Gorantla, Santhi;Makarov, Edward;Roy, Deepa;Finke-Dwyer, Jennifer;Murrin, L. Charles;Gendelman, Howard E.;Poluektova, Larisa

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慢性HIV-1感染通常会影响受感染人类宿主的行为、认知和运动功能,通常称为HIV-1相关神经认知障碍(HAND)。这在一定程度上是白细胞进入脑血管周围区域的结果。这些细胞通过引发血脑屏障和神经网络功能障碍而促进病毒感染和疾病。以前的工作表明,内源性大麻素系统调节神经免疫,因此神经元和神经胶质功能。在此,我们研究了CB 2 R受体在小鼠HIV-1脑炎(HIVE)中的表达以及高选择性CB 2 R激动剂Gp 1a调节疾病的能力。将HIV-1感染的人单核细胞衍生的巨噬细胞注射到用人外周血淋巴细胞(hu-PBL/HIVE)重建的免疫缺陷小鼠的尾状核和壳核中。hu-PBL/HIVE小鼠的脑显示小胶质细胞活化和CB 2 R的表达增加,但不显示CB 1 R或GPR 55。Gp 1a实质上减少了人类细胞向小鼠脑中的浸润,并减少了HLA DQ激活。Gp 1a下调人脾细胞CCR 5的表达,并增加Fas配体的表达。我们的研究结果支持CB 2受体激动剂可能是HAND的可行治疗候选者的观点。
Chronic HIV-1 infection commonly affects behavioral, cognitive, and motor functions in the infected human host and is commonly referred to as HIV-1-associated neurocognitive disorders (HAND). This occurs, in measure, as a consequence of ingress of leukocytes into brain perivascular regions. Such cells facilitate viral infection and disease by eliciting blood–brain barrier and neuronal network dysfunctions. Previous works demonstrated that the endocannabinoid system modulates neuroimmunity and as such neuronal and glial functions. Herein, we investigated CB2R receptor expression in murine HIV-1 encephalitis (HIVE) and the abilities of a highly selective CB2R agonist, Gp1a, to modulate disease. HIV-1-infected human monocyte-derived macrophages were injected into the caudate and putamen of immunodeficient mice reconstituted with human peripheral blood lymphocytes (hu-PBL/HIVE). Brains of hu-PBL/HIVE mice showed microglial activation and increased expression of CB2R, but not CB1R or GPR55. Gp1a substantively reduced infiltration of human cells into the mouse brain and reduced HLA DQ activation. Gp1a down modulated CCR5 expression on human cells in the spleen with an increase in Fas ligand expression. Our results support the notion that CB2 receptor agonists may be a viable therapeutic candidate for HAND.
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DOI: 10.4049/jimmunol.0902962
发表时间: 2010-01-15
期刊: Journal of immunology (Baltimore, Md. : 1950)
影响因子: --
作者:
Eggert D;Dash PK;Gorantla S;Dou H;Schifitto G;Maggirwar SB;Dewhurst S;Poluektova L;Gelbard HA;Gendelman HE
通讯作者: Gendelman HE
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发表时间: 2000-08-01
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