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• W2077597042 abstract "Peroxisome proliferators (PPs) cause rodent liver enlargement and tumors. In vitro, PPs induce rat and mouse hepatocyte DNA synthesis and suppress apoptosis, a response mimicked by exogenous tumor necrosis factor α (TNFα). Here, we determine the role of TNF receptor 1 (TNFR1), TNF receptor 2 (TNFR2), and nuclear factor κ beta (NFκB) in the response of mouse hepatocytes to the PP, nafenopin. Nafenopin (50 μmol/L) induced DNA synthesis as measured by bromodeoxyuridine (BrdU) incorporation, suppressed cell death as measured by Hoechst 33258 staining, induced peroxisomal β-oxidation as measured by cyanide insensitive palmitoyl CoA oxidation (PCO) and caused activation of nuclear factor kappa β (NFκB) as determined by electrophoretic mobility gel shift assay (EMSA). The induction of DNA synthesis and the suppression of apoptosis in response to nafenopin was abrogated completely by blocking antibodies to TNFR1 but not to TNFR2. In contrast, the induction of peroxisomal β-oxidation by nafenopin was not blocked by the anti-TNFR1 antibody. Next, we evaluated the response of hepatocytes to interleukin-1 (IL-1), another proinflammatory cytokine. IL-1α (2.5 ng/mL) and, to a lesser extent, IL-1β (5 ng/mL), shared the ability of TNFα to induce DNA synthesis and suppress apoptosis. In addition, anti–IL-1 receptor, type 1/p80 (IL-1R) antibodies were able to abrogate the response to nafenopin. IL-1α was still able to perturb hepatocyte growth in the presence of the anti-TNFR1 antibody suggesting that IL-1α acts independently rather than by elaborating TNFα. In summary, these data provide additional evidence for a role for hepatic cytokines in the perturbation of hepatocyte growth by PPs such as nafenopin." @default.
• W2077597042 created "2016-06-24" @default.
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• W2077597042 date "1999-12-01" @default.
• W2077597042 modified "2023-09-28" @default.
• W2077597042 title "Role for tumor necrosis factor ? receptor 1 and interleukin-1 receptor in the suppression of mouse hepatocyte apoptosis by the peroxisome proliferator nafenopin" @default.
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• W2077597042 doi "https://doi.org/10.1002/hep.510300612" @default.
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