Abstract
BackgroundHuman T-cell leukemia virus (HTLV-1) is a lymphotropic retrovirus associated to adult T cell leukemia (ATL) and to non-neoplastic inflammatory conditions affecting the central nervous system, lung or skin. The inflammatory disorders associated to HTLV-1 are mediated by different proinflammatory cytokines as IL-1α, IL-6, TNF-α. The release and the role of IL-17 is still debated. Aims of this study were to analyze IL-17 induction by HTLV-1 infection and to determine whether resveratrol (RES) is able to down regulate the pathway of cytokines production either in HTLV-1 chronically infected MT-2 cell line or in human CD4+ cells infected in vitro with HTLV-1.MethodsMT-2 and HTLV-1 infected CD4+ cells were analyzed for proinflammatory cytokine production before or after RES treatment. The concentrations of IL-17, IL-1α, IL-6, and TNF-α were measured in cell culture supernatants by ELISA and SearchLight™ technology. The IL-17 mRNA expression was evaluated by RT-PCR. NF-kB activation was detected by non-radioactive, Electro Mobility Shift Assay (EMSA). HTLV-1 RNA expression was detected by Real-time-PCR (RQ-PCR).ResultsWe found that RES is capable of inducing a dose-dependent inhibition of IL-1α, IL-6 and TNF-α production in vitro and can down regulate the expression of IL-17 at both mRNA and protein levels in HTLV-1 infected cells. This effect was associated with a dose-dependent inhibition of the of the nuclear factor kappa-B (NF-kB) activity. Conversely, RES did not apparently affect HTLV-1 proliferation.ConclusionsThese results support the anti-inflammatory properties of RES, suggesting that it might be a useful therapeutic agent for the treatment of HTLV-1 related inflammatory diseases.
Highlights
Human T-cell leukemia virus (HTLV-1) is a lymphotropic retrovirus associated to adult T cell leukemia (ATL) and to non-neoplastic inflammatory conditions affecting the central nervous system, lung or skin
Monitoring of cytokines production in MT-2 and HTLV-1 infected CD4 + lymphocytes In order to evaluate the production of cytokines induced by an HTLV-1 infection we analyzed the kinetics of IL17, IL-1α, IL-6 and TNF-α production in the cell culture supernatants of MT-2 cells and of peripheral T CD4+ cells infected in vitro with HTLV-1
In the present study we investigated the effects of RES on proinflammatory cytokines production from MT-2 cell line and from peripheral healthy donors CD4+ lymphocytes infected in vitro by HTLV-1
Summary
Human T-cell leukemia virus (HTLV-1) is a lymphotropic retrovirus associated to adult T cell leukemia (ATL) and to non-neoplastic inflammatory conditions affecting the central nervous system, lung or skin. Identified as the etiological agent of ATL it was successively associated with progressive neurological disorders such as the HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a chronic inflammatory disease of the central nervous system [2]. The HTLV-1 associated disorders HAM/TSP is characterized by spontaneous proliferation of CD4+ lymphocytes that harbor a provirus, which appear capable of promoting an active expansion of infected T cells. HTLV-1 is capable to infect CD4+ T and CD8+ T cells in vitro [5] and to immortalize healthy CD4+ T cells that undergo to an active expansion and proliferation [6].
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