Alteration of liver immunity by increasing inflammatory response during co-administration of methamphetamine and atazanavir
Alteration of liver immunity by increasing inflammatory response during co-administration of methamphetamine and atazanavir
复制标题
甲基苯丙胺和阿扎那韦联合给药期间通过增加炎症反应改变肝脏免疫力
DOI：
10.1080/08923973.2020.1745829
复制
发表时间：
2020-04-06
影响因子：
3.3
通讯作者：
Wang, Yong
中科院分区：
文献类型：
--
作者：
Li, Yanfei;Li, Sangsang;Wang, Yong
摘要 目的：甲基苯丙胺（METH）的使用在 HIV 感染者中很普遍。先前的研究表明，冰毒和艾滋病毒蛋白酶抑制剂都会对线粒体呼吸代谢和肝神经系统产生影响。本研究旨在研究冰毒和HIV蛋白酶抑制剂对肝免疫功能的联合作用。材料与方法：基于小鼠模型肝脏RNA-seq获得的差异表达基因，采用qRT-PCR和流式细胞术检测CD48和具有胶原结构的巨噬细胞受体（MARCO）的表达水平，并采用qRT-PCR和ELISA测定细胞因子IL-1β、IL-6、IL-8、IL-10、IFN-γ、IFN-β和TNF-α的表达和分泌。 THP-1 衍生的巨噬细胞。结果：我们的结果表明，与对照组相比，METH-阿扎那韦联合治疗后 CD48 分子显着下调，并且 CD48 的表达水平随着 METH 浓度的增加而降低。 MARCO 分子增加，尤其是在较大剂量的冰毒和阿扎那韦治疗时。此外，在METH-阿扎那韦存在下，一系列促炎细胞因子TNF-α、IL-1β、IL-6和IL-8的表达和分泌增加，而抗炎细胞因子IL-10的表达和分泌减少。结论：这些结果表明，METH 和阿扎那韦对肝脏免疫具有联合影响，表明联合治疗可以增强炎症反应并通过 CD48 抑制 NK 细胞活化。
Abstract Objective: Use of methamphetamine (METH) is prevalent among HIV-infected individuals. Previous research has shown that both METH and HIV protease inhibitors exert influences on mitochondrial respiratory metabolism and hepatic nervous system. This study aims to study the joint effect of METH and HIV protease inhibitors on hepatic immune function. Materials and methods: Based on the differentially expressed genes obtained from RNA-seq of the liver from mouse model, the expression levels of CD48 and Macrophage Receptor with Collagenous Structure (MARCO) were examined using qRT-PCR and flow cytometry, and the expression and secretion of cytokines IL-1β, IL-6, IL-8, IL-10, IFN-γ, IFN-β, and TNF-α were determined using qRT-PCR and ELISA in THP-1-derived macrophages. Results: Our results indicated that compared with the control group, CD48 molecules were significantly down-regulated by METH–atazanavir co-treatment, and the expression level of CD48 decreased as METH concentration increases. MARCO molecules were increased, especially at larger doses of METH and atazanavir treatment. In addition, in the presence of METH–atazanavir, the expression and secretion of a series of pro-inflammatory cytokines TNF-α, IL-1β, IL-6, and IL-8 increased while the expression and secretion of anti-inflammatory cytokine IL-10 decreased. Conclusion: These results demonstrated that METH and atazanavir had a combined impact on the liver immunity, suggesting that the co-treatment could enhance inflammatory response and suppress NK cell activation via CD48.