Induction of pro-inflammatory cytokines by human T-cell leukemia virus type-1 Tax protein as determined by multiplexed cytokine protein array analyses of human dendritic cells
| Autor: | Pooja Jain, Zafar K. Khan, Brian Wigdahl, Jaya Ahuja, Veronique Lepoutre |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Chemokine
medicine.medical_treatment Protein Array Analysis Enzyme-Linked Immunosorbent Assay In Vitro Techniques Article Proinflammatory cytokine Immune system immune system diseases medicine Humans Antigen-presenting cell Pharmacology Dose-Response Relationship Drug biology NF-kappa B virus diseases Dendritic Cells Gene Products tax General Medicine Dendritic cell Cytokine Immunology biology.protein Cytokines Cytokine secretion Chemokines CD8 Signal Transduction |
| Zdroj: | Biomedicine & Pharmacotherapy. 61:201-208 |
| ISSN: | 0753-3322 |
| DOI: | 10.1016/j.biopha.2007.02.006 |
| Popis: | Human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is characterized by a hyperstimulated immune response, including elevated levels of inflammatory cytokines/chemokines and oligoclonal expansion of virus-specific CD8(+) T cells in the cerebrospinal fluid. Studies have shown that the HTLV-1 transactivator protein Tax is available for immune recognition by antigen presenting cells (APCs), such as dendritic cells (DCs). DCs are relevant to the pathogenesis of HAM/TSP because the presentation of Tax peptides by activated DCs to naive CD8(+) T cells may play an important role in the induction of the Tax-specific immune response that is observed in HAM/TSP. In this study, a human cytokine protein array was used to study the secretion of cytokines by monocyte-derived DCs (MDDCs) exposed to Tax. Of the 16 cytokines analyzed, 6 cytokines were secreted in significantly high amounts (> or =2-fold), including Th1 cytokines (IFN-gamma, IL-12, and TNF-alpha) and C-C chemokines (Eotaxin, MCP-1, and MCP-3). Selected cytokines were further examined at two concentrations of Tax and at two time periods. Furthermore, a transient exposure to Tax did not result in any cytokine production when examined at three different time points after exposure, indicating that a prolonged presence of Tax is required for its activity. Finally, inhibition of the NF-kappaB signaling pathway by specific inhibitors, abrogated Tax-mediated cytokine secretion. Collectively, these findings suggest a role for Tax-induced cytokine secretion from MDDCs, which may be critical for the cellular activation and tissue damage that has been observed in HAM/TSP. |
| Databáze: | OpenAIRE |
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