HIV-1 Tat Protein-Mediated Inflammatory Response Inhibits the Erythroid Hematopoietic Support Function of Bone Marrow Mesenchymal Stem Cells.

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 (κ) 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 , , , , , , κ, and -κ was significantly upregulated by Tat protein. In conclusion, Tat protein induces the inflammatory response of BMSCs by activating the -κ pathway to inhibit the erythroid hematopoietic support function of BMSCs.