Department of Forensic Science, School of Basic Medical Science, Central South University, Changsha, Hunan, P.R. China.
Department of Immunology, School of Basic Medical Science, Central South University, Changsha, Hunan, P.R. China.
Immunopharmacol Immunotoxicol. 2020 Jun;42(3):237-245. doi: 10.1080/08923973.2020.1745829. Epub 2020 Apr 6.
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. 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. 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. 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 CD48.
METH 的使用在感染 HIV 的个体中很普遍。先前的研究表明，METH 和 HIV 蛋白酶抑制剂都对线粒体呼吸代谢和肝神经系统有影响。本研究旨在研究 METH 和 HIV 蛋白酶抑制剂对肝免疫功能的联合作用。基于从小鼠模型肝脏的 RNA-seq 获得的差异表达基因，使用 qRT-PCR 和流式细胞术检查 CD48 和具有胶原结构的巨噬细胞受体（MARCO）的表达水平，并使用 qRT-PCR 和 ELISA 测定 THP-1 衍生的巨噬细胞中细胞因子 IL-1β、IL-6、IL-8、IL-10、IFN-γ、IFN-β 和 TNF-α的表达和分泌。我们的结果表明，与对照组相比，METH-atazanavir 共同处理显著下调 CD48 分子，并且 CD48 的表达水平随着 METH 浓度的增加而降低。MARCO 分子增加，特别是在较大剂量的 METH 和 atazanavir 治疗时。此外，在 METH-atazanavir 存在的情况下，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。这些结果表明 METH 和 atazanavir 对肝脏免疫有联合影响，提示联合治疗可能增强炎症反应并抑制 NK 细胞激活 CD48。
