Buprenorphine decreases the CCL2-mediated chemotactic response of monocytes.
Buprenorphine decreases the CCL2-mediated chemotactic response of monocytes.
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DOI：
10.4049/jimmunol.1302647
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发表时间：
2015-04-01
期刊：
影响因子：
--
通讯作者：
Berman JW
中科院分区：
文献类型：
--
作者：
Carvallo L;Lopez L;Che FY;Lim J;Eugenin EA;Williams DW;Nieves E;Calderon TM;Madrid-Aliste C;Fiser A;Weiss L;Angeletti RH;Berman JW
尽管cART成功，但大约60%的HIV感染者表现出HIV相关的神经认知障碍（HAND）。CCL2在HAND感染者的中枢神经系统中升高，介导单核细胞流入中枢神经系统，这在神经艾滋病中是至关重要的。许多感染艾滋病毒的阿片类药物滥用者神经炎症增加，可能会增加HAND。丁丙诺啡用于治疗鸦片成瘾。然而，很少有研究考察其对HIV神经发病机制的影响。我们发现丁丙诺啡降低了单核细胞的趋化表型。丁丙诺啡减少响应CCL2的膜突起的形成。它还能降低CCL2诱导的趋化性，并介导CCL2介导的受体内化后CCL2受体重新插入细胞膜的延迟，提示丁丙诺啡的作用机制。ccl2诱导迁移的信号通路包括p38 MAPK和连接蛋白JAM-A磷酸化的增加。我们发现丁丙诺啡在ccl2处理的单核细胞中降低了这些磷酸化。使用DAMGO， CTAP和no - bni，我们证明丁丙诺啡对CCL2信号传导的影响是阿片受体介导的。为了确定丁丙诺啡抑制CCL2诱导的单核细胞迁移的其他潜在机制，我们进行了蛋白质组学分析，以表征在CCL2治疗后磷酸化被丁丙诺啡抑制的单核细胞中的其他蛋白质。Leukosialin和S100A9被鉴定出来，以前没有发现它们参与单核细胞迁移。我们建议丁丙诺啡限制ccl2介导的单核细胞向中枢神经系统的迁移，从而减少HAND的神经炎症特征。我们的研究结果强调了丁丙诺啡作为神经炎症和成瘾的治疗方法的使用。
Despite successful cART, approximately 60% of HIV infected people exhibit HIV associated neurocognitive disorders (HAND). CCL2 is elevated in the CNS of infected people with HAND and mediates monocyte influx into the CNS, which is critical in neuroAIDS. Many HIV infected opiate abusers have increased neuroinflammation that may augment HAND. Buprenorphine is used to treat opiate addiction. However, there are few studies that examine its impact on HIV neuropathogenesis. We show that buprenorphine reduces the chemotactic phenotype of monocytes. Buprenorphine decreases the formation of membrane projections in response to CCL2. It also decreases CCL2-induced chemotaxis and mediates a delay in reinsertion of the CCL2 receptor, CCR2, into the cell membrane after CCL2-mediated receptor internalization, suggesting a mechanism of action of buprenorphine. Signaling pathways in CCL2-induced migration include increased phosphorylation of p38 MAPK and of the junctional protein JAM-A. We show that buprenorphine decreases these phosphorylations in CCL2-treated monocytes. Using DAMGO, CTAP, and Nor-BNI, we demonstrate that the effect of buprenorphine on CCL2 signaling is opioid receptor mediated. To identify additional potential mechanisms by which buprenorphine inhibits CCL2-induced monocyte migration, we performed proteomic analyses to characterize additional proteins in monocytes whose phosphorylation after CCL2 treatment was inhibited by buprenorphine. Leukosialin and S100A9, were identified and had not been shown previously be involved in monocyte migration. We propose that buprenorphine limits CCL2-mediated monocyte transmigration into the CNS, thereby reducing neuroinflammation characteristic of HAND. Our findings underscore the use of buprenorphine as a therapeutic for neuroinflammation as well as for addiction.
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影响因子：
5.5
作者：
Ayala, JM;Goyal, S;Hanlon, WA
通讯作者：
Hanlon, WA
影响因子：
4.8
作者：
Garcia Lopez, M. A.;Aguado Martinez, A.;Fischer, T.
通讯作者：
Fischer, T.
影响因子：
7.4
作者：
Fleitz, Antoine;Nieves, Edward;Che, Fa-Yun
通讯作者：
Che, Fa-Yun
DOI：
10.1084/jem.190.9.1351
发表时间：
1999-11-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Del Maschio A;De Luigi A;Martin-Padura I;Brockhaus M;Bartfai T;Fruscella P;Adorini L;Martino G;Furlan R;De Simoni MG;Dejana E
通讯作者：
Dejana E
影响因子：
5.3
作者：
Eugenin, EA;Osiecki, K;Berman, JW
通讯作者：
Berman, JW