Effect of tenofovir on nucleotidases and cytokines in HIV-1 target cells
| Autor: | John V. Fahey, Charles R. Wira, Zheng Shen, Marta Rodriguez-Garcia, Jack E. Bodwell, Nabanita Biswas, Sarah G. Crist |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
CD4-Positive T-Lymphocytes
Time Factors Nucleotidase activity Organophosphonates lcsh:Medicine Inflammation Biology Pharmacology Lymphocyte Activation Gene Expression Regulation Enzymologic 5'-nucleotidase 03 medical and health sciences Nucleotidase Gene expression medicine Humans Immunologic Factors Secretion Tenofovir lcsh:Science 5'-Nucleotidase 030304 developmental biology 0303 health sciences Multidisciplinary Innate immune system Dose-Response Relationship Drug 030306 microbiology Adenine Macrophages lcsh:R Dendritic Cells Immunity Innate 3. Good health Immunology HIV-1 Cytokines Tumor necrosis factor alpha lcsh:Q medicine.symptom Research Article |
| Zdroj: | PLoS ONE, Vol 8, Iss 10, p e78814 (2013) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Tenofovir (TFV) has been widely used for pre-exposure prophylaxis of HIV-1 infection with mixed results. While the use of TFV in uninfected individuals for prevention of HIV-1 acquisition is actively being investigated, the possible consequences of TFV exposure for the HIV-target cells and the mucosal microenvironment are unknown. In the current study, we evaluated the effects of TFV treatment on blood-derived CD4⁺ T cells, monocyte-derived macrophages and dendritic cells (DC). Purified HIV-target cells were treated with different concentrations of TFV (0.001-1.0 mg/ml) for 2 to 24 hr. RNA was isolated and RT-PCR was performed to compare the levels of mRNA expression of nucleotidases and pro-inflammatory cytokine genes (MIP3α, IL-8 and TNFα) in the presence or absence of TFV. We found that TFV increases 5'-ecto-nucleotidase (NT5E) and inhibits mitochondrial nucleotidase (NT5M) gene expression and increases 5' nucleotidase activity in macrophages. We also observed that TFV stimulates the expression and secretion of IL-8 by macrophages, DC, and activated CD4⁺ T cells and increases the expression and secretion of MIP3α by macrophages. In contrast, TFV had no effect on TNFα secretion from macrophages, DC and CD4⁺ T cells. Our results demonstrate that TFV alters innate immune responses in HIV-target cells with potential implications for increased inflammation at mucosal surfaces. As new preventive trials are designed, these findings should provide a foundation for understanding the effects of TFV on HIV-target cells in microbicide trials. |
| Databáze: | OpenAIRE |
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