title: Downregulation of proinflammatory cytokines in HTLV-1-infected T cells by Resveratrol.
abstract: 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. 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.
  
  
  
  MT-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).
  
  
  
  We 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.
  
  
  
  These 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.
authors.affiliation: Institute of Translational Pharmacology (IFT), National Research Council (CNR), Via Fosso del Cavaliere 100, 00133, Rome, Italy. mariapia.fuggetta@ift.cnr.it.
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Fuggetta
authors.affiliation: Laboratory of Clinical Pathology and Microbiology, San Gallicano Dermatologic Institute, Via Elio Chianesi, 53, 00144, Rome, Italy. valentina.bordignon@ifo.gov.it.
authors.forename: Valentina
authors.initials: V
authors.lastname: Bordignon
authors.affiliation: Institute of Translational Pharmacology (IFT), National Research Council (CNR), Via Fosso del Cavaliere 100, 00133, Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Cottarelli
authors.affiliation: Department of System Medicine, University of Rome "Tor Vergata", Via Montpellier 1, 00133, Rome, Italy.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Macchi
authors.affiliation: Department of Biochemical Science and Surgery, University of Rome "Tor Vergata", Via Montpellier 1, 00133, Rome, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Frezza
authors.affiliation: Laboratory of Clinical Pathology and Microbiology, San Gallicano Dermatologic Institute, Via Elio Chianesi, 53, 00144, Rome, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Cordiali-Fei
authors.affiliation: Laboratory of Clinical Pathology and Microbiology, San Gallicano Dermatologic Institute, Via Elio Chianesi, 53, 00144, Rome, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Ensoli
authors.affiliation: Institute of Translational Pharmacology (IFT), National Research Council (CNR), Via Fosso del Cavaliere 100, 00133, Rome, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Ciafrè
authors.affiliation: Department of Chemical, Biological, Pharmaceutical, and Environmental Sciences, University of Messina, 98166, Messina, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Marino-Merlo
authors.affiliation: Institute of Translational Pharmacology (IFT), National Research Council (CNR), Via Fosso del Cavaliere 100, 00133, Rome, Italy.|Department of Chemical, Biological, Pharmaceutical, and Environmental Sciences, University of Messina, 98166, Messina, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Mastino
authors.affiliation: Institute of Translational Pharmacology (IFT), National Research Council (CNR), Via Fosso del Cavaliere 100, 00133, Rome, Italy.
authors.forename: Giampietro
authors.initials: G
authors.lastname: Ravagnan
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005786:Gene Expression Regulation / Q000187:drug effects; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D053582:Interleukin-1alpha / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; C508584:IL1A protein, human; C508600:IL6 protein, human; D020381:Interleukin-17; D053582:Interleukin-1alpha; D015850:Interleukin-6; D016328:NF-kappa B; D013267:Stilbenes; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D000077185:Resveratrol
keywords: HTLV-1; Inflammatory cytokines; Resveratrol