Although combination antiretroviral therapy is widely used to treat HIV-1 infection, anemia affects the health and quality of life in a large number of these patients. The proliferation and differentiation of bone marrow mesenchymal stem cells (BMSCs), as important support cells in the hematopoietic microenvironment, can be affected by HIV-1 Tat protein. In this study, we explored the mechanism underlying the effect of Tat protein on the hematopoietic support function of BMSCs in erythroid commitment. BMSCs were treated with Tat protein or transfected with Tat mRNA and cocultured with hematopoietic stem cells (HSCs) to detect the number of erythroid colony-forming units (CFUs) and the proportion of mature red blood cells from HSCs. Subsequently, the expression level of a series of erythroid hematopoietic support factors and inflammatory factors in BMSCs after Tat treatment were analyzed. Then, the activation effect of Tat on the mitogen-activated protein kinase/nuclear factor kappa-B (MAPK/NF-κB) pathway, which is an important inflammatory response signaling pathway, was evaluated. The results showed that the number of erythroid CFUs and the production of mature red blood cells supported by BMSCs treated with Tat protein were significantly reduced and the expression of a series of erythroid supporting factors of BMSCs were significantly decreased by Tat protein. Tat-treated BMSCs highly express a variety of inflammatory mediators. Moreover, the expression of P38, p-p38, ERK1/2, p-ERK1/2, JNK1/2, p-JNK1/2, NF-κB, and p-NF-κB was significantly upregulated by Tat protein. In conclusion, Tat protein induces the inflammatory response of BMSCs by activating the MAPK/NF-κB pathway to inhibit the erythroid hematopoietic support function of BMSCs.

中文翻译：

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HIV-1 Tat蛋白介导的炎症反应抑制骨髓间充质干细胞的红系造血支持功能

尽管联合抗逆转录病毒疗法广泛用于治疗 HIV-1 感染，但贫血会影响大量此类患者的健康和生活质量。骨髓间充质干细胞（BMSCs）作为造血微环境中的重要支持细胞，其增殖和分化可受到HIV-1 Tat蛋白的影响。在这项研究中，我们探讨了 Tat 蛋白对 BMSCs 在红系定型中造血支持功能影响的潜在机制。将BMSCs用Tat蛋白处理或用Tat mRNA转染并与造血干细胞（HSCs）共培养以检测红细胞集落形成单位（CFUs）的数量和来自HSCs的成熟红细胞的比例。随后，分析Tat处理后BMSCs中一系列红系造血支持因子和炎症因子的表达水平。然后，Tat 对丝裂原活化蛋白激酶/核因子 kappa-B 的激活作用（评估了MAPK/NF-κB )通路，这是一种重要的炎症反应信号通路。结果表明，经Tat蛋白处理后的BMSCs支持的红系CFUs数量和成熟红细胞的产生显着降低，Tat蛋白显着降低BMSCs一系列红系支持因子的表达。Tat 处理的 BMSCs 高度表达多种炎症介质。此外，P38、p-p38、ERK1/2、p-ERK1/2、JNK1/2、p-JNK1/2 、 NF -κB和p -NF-κB的表达被 Tat 蛋白显着上调。综上所述，Tat蛋白通过激活MAPK/NF -κB通路抑制BMSCs的红系造血支持功能，从而诱导BMSCs发生炎症反应。