CCL5/RANTES gene deletion attenuates opioid-induced increases in glial CCL2/MCP-1 immunoreactivity and activation in HIV-1 Tat-exposed mice.
CCL5/RANTES gene deletion attenuates opioid-induced increases in glial CCL2/MCP-1 immunoreactivity and activation in HIV-1 Tat-exposed mice.
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DOI：
10.1007/s11481-008-9127-1
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发表时间：
2008-12
影响因子：
6.2
通讯作者：
Hauser, Kurt F.
中科院分区：
文献类型：
--
作者：
El-Hage, Nazira;Bruce-Keller, Annadora J.;Knapp, Pamela E.;Hauser, Kurt F.
关键词：
为了评估CC-趋化因子配体5（CCL 5）/RANTES在阿片类药物滥用和人类免疫缺陷病毒1型（HIV-1）合并症中的作用，在野生型和CCL 5敲除小鼠中评估了全身吗啡和纹状体内HIV-1达特对巨噬细胞/小胶质细胞和星形胶质细胞活化的影响。向小鼠纹状体内注射载体或达特，7天后评估。通过时间释放植入物向一些Tat注射的小鼠施用吗啡（5 mg/天，s.c.持续5天）。与野生型小鼠相比，在达特和吗啡联合暴露后7天，CCL 5（−/−）中的神经胶质活化显著减少。此外，与野生型小鼠相比，注射达特±吗啡的CCL 5（−/−）小鼠中3-硝基酪氨酸免疫阳性巨噬细胞/小胶质细胞的百分比显著降低，表明CCL 5有助于HIV-1脑炎中的亚硝化应激。在CCL 5（-/-）小鼠中，与野生型小鼠相比，达特±吗啡诱导的神经胶质增生减少，同时CCL 2/MCP-1免疫反应性星形胶质细胞和巨噬细胞/小胶质细胞的比例显着下降。在基因敲除小鼠中，无论是单独的达特还是与吗啡联合使用，都不能增加CCL 2免疫反应性星形胶质细胞的比例，高于注射溶剂对照组的百分比。大胶质细胞/小胶质细胞不同，显示出适度的，虽然显着的，增加的比例与组合达特和吗啡暴露的CCL 2阳性细胞，表明CCL 5优先影响CCL 2表达的星形胶质细胞。因此，CCL 5介导由达特和吗啡引起的神经胶质活化，从而加重阿片类药物滥用者和非滥用者中的HIV-1神经发病机制。CCL 5涉及介导由星形胶质细胞产生的CCL 2的甘氨酸驱动的扩增以及由此产生的巨噬细胞/小胶质细胞募集和活化。
To assess the role of CC-chemokine ligand 5 (CCL5)/RANTES in opiate drug abuse and human immunodeficiency virus type 1 (HIV-1) comorbidity, the effects of systemic morphine and intrastriatal HIV-1 Tat on macrophage/microglial and astroglial activation were assessed in wild-type and CCL5 knockout mice. Mice were injected intrastriatally with vehicle or Tat and assessed after 7 days. Morphine was administered to some Tat-injected mice via time-release implant (5 mg/day, s.c. for 5 days) starting at 2 days post injection. Glial activation was significantly reduced in CCL5(−/−) compared to wild-type mice at 7 days following combined Tat and morphine exposure. Moreover, the percentage of 3-nitrotyrosine immunopositive macrophages/microglia was markedly reduced in CCL5(−/−) mice injected with Tat ± morphine compared to wild-type counterparts, suggesting that CCL5 contributes to nitrosative stress in HIV-1 encephalitis. In CCL5(−/−) mice, the reductions in Tat ± morphine-induced gliosis coincided with significant declines in the proportion of CCL2/MCP-1-immunoreactive astrocytes and macrophages/microglia compared to wild-type counterparts. In knockout mice, neither Tat alone nor in combination with morphine increased the proportion of CCL2-immunoreactive astrocytes above percentages seen in vehicle-injected controls. Macrophages/microglia differed showing modest, albeit significant, increases in the proportion of CCL2-positive cells with combined Tat and morphine exposure, suggesting that CCL5 preferentially affects CCL2 expression by astroglia. Thus, CCL5 mediates glial activation caused by Tat and morphine, thereby aggravating HIV-1 neuropathogenesis in opiate abusers and non-abusers. CCL5 is implicated as mediating the cytokine-driven amplification of CCL2 production by astrocytes and resultant macrophage/microglial recruitment and activation.
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影响因子：
5
作者：
Chen, CG;Li, J;Liu-Chen, LY
通讯作者：
Liu-Chen, LY
DOI：
10.1016/0736-5748(94)00061-7
发表时间：
1995-06-01
影响因子：
1.8
作者：
BENVENISTE, EN;TANG, LP;LAW, RM
通讯作者：
LAW, RM
DOI：
10.1073/pnas.94.26.14742
发表时间：
1997-12-23
影响因子：
11.1
作者：
Edinger, AL;Mankowski, JL;Doms, RW
通讯作者：
Doms, RW
影响因子：
5.3
作者：
Eugenin, EA;Osiecki, K;Berman, JW
通讯作者：
Berman, JW
影响因子：
6.2
作者：
Bidlack, Jean M.;Khimich, Maxim;Tipton, Christopher M.
通讯作者：
Tipton, Christopher M.