Hypoxia Potentiates LPS-Mediated Cytotoxicity of BV2 Microglial Cells In Vitro by Synergistic Effects on Glial Cytokine and Nitric Oxide System

Frey D, Jung S, Brackmann F, Richter-Kraus M, Trollmann R (2015)


Publication Type: Journal article

Publication year: 2015

Journal

Book Volume: 46

Pages Range: 321-8

Journal Issue: 5

DOI: 10.1055/s-0035-1562924

Abstract

Microglial activation due to a variety of stimuli induces secretion of neurotoxic substances including inflammatory cytokines and nitric oxide (NO). Clinical studies indicate a cross-link between inflammatory and hypoxia-regulated pathways suggesting that bacterial infections markedly sensitize the immature brain to hypoxic injury.The impact of inflammation and hypoxia on interleukin (IL)-1?, IL-6, tumor necrosis factor ? (TNF-?), and NO secretion and microglia-induced cytotoxicity was investigated exposing BV2 cells to lipopolysaccharides (LPS) and hypoxia (1% O2). Cytotoxicity, NO, and cytokine release was quantified by MTS and Griess assays and by enzyme-linked immunosorbent assays, respectively.LPS exposure of BV2 cells induced a significant, persistent production of NO, IL-1?, IL-6, and TNF-?. Even after LPS removal, ongoing NO and cytokine secretion was observed. Hypoxia mediated exclusively a significant, short-term IL-1? increase, but enhanced LPS-induced cytokine and NO secretion significantly. In addition, LPS-induced supernatants exhibited a stronger cytotoxic effect in glial and neuronal cells than LPS exposition (p < 0.001). Hypoxia potentiated LPS-induced cytotoxicity.Present data prove that LPS-induced soluble factors rather than LPS exposure mediate microglial toxicity under conditions of hypoxia in vitro. Apart from potential protective effects of the hypoxia-inducible transcription factor (HIF)-1? system, activation of proinflammatory pathways may markedly sensitize microglial cells to promote hypoxia-induced injuries of the developing brain.

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How to cite

APA:

Frey, D., Jung, S., Brackmann, F., Richter-Kraus, M., & Trollmann, R. (2015). Hypoxia Potentiates LPS-Mediated Cytotoxicity of BV2 Microglial Cells In Vitro by Synergistic Effects on Glial Cytokine and Nitric Oxide System. Neuropediatrics, 46(5), 321-8. https://doi.org/10.1055/s-0035-1562924

MLA:

Frey, Daniel, et al. "Hypoxia Potentiates LPS-Mediated Cytotoxicity of BV2 Microglial Cells In Vitro by Synergistic Effects on Glial Cytokine and Nitric Oxide System." Neuropediatrics 46.5 (2015): 321-8.

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