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• W2000690104 abstract "Proinflammatory mediators have been implicated in demyelinating disorders, including multiple sclerosis, whereas it has been proposed that the anti-inflammatory cytokines interleukin- (IL-) 4 and IL-10 participate in disease recovery. The present study analysed the effect of interferon-gamma (IFN-gamma) and bacterial endotoxin (lipopolysaccharide, LPS) on proliferation and survival of progenitors and differentiated oligodendrocytes. We also investigated the presence of receptors for IL-4 and IL-10 in oligodendroglial cells and explored a possible protective action of IL-4 and IL-10 in cultures following LPS/IFN-gamma. Finally, the role of endogenous nitric oxide (NO) on cell viability and the modulatory action of IL-4 and IL-10 on inducible nitric oxide synthase (iNOS) expression were also analysed. We report that LPS and/or IFN-gamma reduced proliferation and viability of oligodendroglial cells. Cell death, presumably by apoptosis as evidence by TUNEL and Annexin V binding, was observed following LPS/IFN-gamma, progenitors being more sensitive than differentiated cells. At both developmental stages, LPS/IFN-gamma-treated cultures expressed iNOS protein and released micromolar concentrations of NO. In progenitors, LPS/IFN-gamma-mediated cell damage was partially dependent on endogenous NO production, whereas NO was fundamental for cytotoxicity of differentiated oligodendrocytes. Both cell types expressed mRNA for IL-4 and IL-10 receptors and expression of IL-10 receptors at the protein level was also demonstrated. Treatment with either cytokine inhibited the expression of iNOS resulting from the proinflammatory stimulation. IL-10 was more effective than IL-4 in suppressing iNOS expression and, interestingly, IL-10 conferred protection against oligodendroglial death evoked by LPS/IFN-gamma. Our data raise the question of whether IL-10 may play a protective role in demyelinating diseases, not only downregulating the function of inflammatory cells but also promoting survival of progenitors and differentiated oligodendrocytes." @default.
• W2000690104 created "2016-06-24" @default.
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• W2000690104 date "2001-02-01" @default.
• W2000690104 modified "2023-10-10" @default.
• W2000690104 title "LPS/IFN-γ cytotoxicity in oligodendroglial cells: role of nitric oxide and protection by the anti-inflammatory cytokine IL-10" @default.
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• W2000690104 doi "https://doi.org/10.1046/j.0953-816x.2000.01412.x" @default.
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