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  • Title: Morphine reduces mouse microglial engulfment induced by lipopolysaccharide and interferon-γ via δ opioid receptor and p38 mitogen-activated protein kinase.
    Author: Ryu JH, Do SH, Han SH, Zuo Z.
    Journal: Neurol Res; 2018 Jul; 40(7):600-606. PubMed ID: 29583107.
    Abstract:
    Objective To investigate the effects of morphine on microglial phagocytosis during neuroinflammation. Methods C8-B4 mouse microglial cells were exposed to various concentrations of morphine after the stimulation with lipopolysaccharide and interferon-γ and then fluorescent immunostaining was performed to assess the percentage of microglia that engulfed fluorescent microspheres in total microglia. Naloxone, β funaltrexamine, or naltrindole was used with 1 μM morphine to assess the involvement of specific opioid receptor. P38 and phosphorylated p38 were determined by Western blotting. A p38 mitogen-activated protein kinase (MAPK) activator (anisomycin 0.1 μM) or inhibitor (SB 203580, 20 μM) was used to determine the involvement of p38 MAPK pathway. Results Morphine decreased lipopolysaccharide and interferon-γ-induced microglial engulfment except the highest concentration (10 μM) and both naloxone and naltrindole (a selective δ opioid receptor antagonist) attenuated morphine effect (p < 0.001). The phosphorylated p38 was up-regulated in lipopolysaccharide and interferon-γ group compared with control group (p < 0.001). This up-regulation was decreased by 1 μM morphine (p < 0.001). However, naltrindole abolished this morphine effect (p = 0.015). SB203580 blocked the increased microglial engulfment induced by lipopolysaccharide and interferon-γ (p < 0.001); whereas, anisomycin enhanced the morphine-induced decrease of engulfment (p < 0.001). Conclusion Morphine reduced mouse microglial engulfment induced by lipopolysaccharide and interferon-γ. This morphine effect seems to be mediated by δ opioid receptor and via p38 MAPK inhibition.
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