101,931 research outputs found

    HSP70 production and inhibition of cell proliferation in molt-4 T-cells after cell-to-cell transmission of HTLV-I: Effect of PGA1

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    Infection with HTLV-I is associated with leukemic transformation of mature CD4(+) T lymphocytes. PGA(1), a powerful inhibitor of tumour cell proliferation, can prevent the clonal expansion of HTLV-I-infected cells following acute infection of cord blood-derived mononuclear cells. Since the antiproliferative effect of PGA(1) on HTLV-I transformed, chronically infected MT-2 cell line was associated with induction of HSP70, we have investigated the effect of PGA(1) on cell cycle progression and HSP70 production in a leukemic T-cell line (Molt-4) shortly after exposure to HTLV-I in a cell-to-cell transmission model. rate of cell proliferation and HSP70 expression were studied within one duplication cycle of Molt-4 cells after exposure to HTLV-I. growth of both control and virus-exposed cultures was inhibited by treatment with PGA(1) (4 mu g/ml) and cell cycling was arrested preferentially at the G(1)/S interphase. synthesis of HSP70 was induced within 3 h by PGA(1) in control and virus-exposed Molt-4 cells and became undetectable from overnight onward, though the protein accumulated in the cells. the arrest of growth was observed from overnight up to 48 h so that treated cells almost missed one cycle. Interestingly, HSP70 transcript and protein persisted at remarkably high levels in molt-4 cells exposed to HTLV-I in the absence of PGA(1), showing that HSP70 expression can be directly activated during primary infection with this human retrovirus. moreover, in these cocultures, treatment with PGA(1) or heat shock was not able to increase further the elevated level of HSP70 found in untreated cocultures, suggesting that during the early period of the virus-transmission phase, HTLV-I could interfere with HSP70 induction by other inducers

    Anti-inflammatory Effect of Resveratrol and Polydatinby In Vitro IL-17 Modulation.

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    Interleukin-17 (IL-17) is a proinflammatory cytokine produced, although not exclusively, by T helper 17 recently identified as a distinct T helper lineage mediating tissue inflammation. IL-17 is known to be involved in a number of chronic disorders although the mechanisms regulating its production in inflammatory disease are still unclear. The beneficial properties of the polyphenolic compound resveratrol including its nti-inflammatory, antioxidant, and antitumor effects, its role in the aging process and in the prevention of heart and neurodegenerative diseases are well-known. In addition, derivatives of resveratrol, including glucosylated molecules as polydatin have been linked to similar beneficial effects. We have investigated the effects of resveratrol and polydatin on the in vitro production of IL-17 in a model of inflammation in vitro. The results obtained by activated human peripheral blood mononuclear cells, stimulated with anti-CD3/anti-CD28 monoclonal antibodies and treated with these polyphenolic compounds at different concentrations show that both decrease IL-17 production in a concentration-dependent manner. This study confirms the anti-inflammatory activity of resveratrol and its derivatives and suggests a potential clinical relevance in the therapy of inflammatory diseases

    IL-2 reverses the inhibition of cytotoxic T-cell responses induced by 5-(3,3' dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC) in vitro

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    One of the major limitations in the use of triazene compounds for inducing increased immunogenicity of tumor cells in vivo (i.e. chemical xenogenization) is the profound immunodepressive activity of these drugs. The present study analysed the inhibitory effects of DTIC on various T-dependent immune responses in mice in an attempt to determine the mechanism of action and appropriate treatments for reverting the immune damage produced by the agent. Results obtained show that treatment with DTIC in vivo produced: (a) inhibition of spleen cell proliferation; (b) reduced IL-2 production in response to allogeneic stimuli; (c) reduction of the generation of IL-2R + CD8 + cells in allogeneic MLC; (d) inhibition of allo-CTL generation. The addition of IL-2 to MLC on day 2 of the co-culture restored full allogeneic CTL responses. These data suggest that exogenous IL-2 could be used to counteract DTIC-induced depression of T-cell reactivity, which is presumably involved in hosts' responses against autochthonous xenogenized tumor cells
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