Domonkos Feher - Classical and Alternative Activation of Cyanobacterium Oscillatoria sp. Lipopolysaccharide-Treated Rat Microglia in vitro.

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      Publication Details (including relevant citation   information):

          Mayer, Alejandro M. S.: Murphy, Joseph; MacAdam, David;   Osterbauer, Christopher; Baseer, Imaan; Hall, Mary L.;    Fehér,   Domonkos; Phillip Williams; Toxicological   Sciences   2016,   149,   484-495.

      Abstract:

      The   purpose of this investigation was to test the hypothesis that an   in vitro exposure to cyanobacterium Oscillatoria sp. LPS might   result in classical and alternative activation of rat neonatal   microglia. Using Escherichia coli LPS-primed microglia as a   positive control, the present study revealed that treatment of   rat microglia with Oscillatoria sp. LPS for 17 h in vitro   resulted in both classical and alternative activation as well as   concomitant pro-inflammatory and anti-inflammatory mediator   release, in a concentration-dependent manner: (1) treatment with   0.1-10,000 ng/ml Oscillatoria sp. LPS resulted in minimal LDH   release, induced concentration-dependent and statistically   significant O2- generation, matrix metalloproteinase-9 (MMP-9)   release, generation of the cytokines tumor necrosis factor-α   (TNF-α) and interleukin-6 (IL-6), and the chemokines macrophage   inflammatory protein-2 (MIP-2/CXCL2), interferon γ-induced   protein 10 kDa (IP-10/CXCL-10), macrophage inflammatory protein   1α (MIP-1α/CCL3), monocyte chemotactic protein-1 (MCP-1/CCL2),   regulated on activation, normal T cell expressed and secreted   (RANTES/CCL5), and the alternative activation cytokine IL-10; (3)   In contrast, treatment with 100,000 ng/mL Oscillatoria sp. LPS   appeared to damage the microglia cell membrane, because it   resulted in minimal O2- generation, statistically significant LDH   release, and a decrease in the generation of all the cytokines   and chemokines investigated, with the exception of interleukin   1-α (IL-1α) and cytokine-induced neutrophil chemoattractant 1   (CINC-1/CXCL1) generation, which was increased. Thus, our results   provide experimental support for our working hypothesis, namely   that Oscillatoria sp. LPS induces classical and alternative   activation of rat brain microglia in vitro in a   concentration-dependent manner, namely 0.1-10,000 ng/ml   Oscillatoria sp. LPS, when microglia cells were shown to be   viable. Furthermore, should cyanobacterium Oscillatoria sp. LPS   gain entry into the CNS, our findings suggest that classical and   alternative activation of rat brain microglia in vivo, might lead   to concomitant mediator release that could result in an interplay   between neuroinflammation and neural repair in a   concentration-dependent manner.

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