• Penglian Wang, Nancy J Rothwell, Emmanuel Pinteaux, and David Brough.
• Faculty of Life Sciences, University of Manchester, Manchester, M13 9PT, UK.
• Brain Res. 2008 Oct 21; 1236: 1-7.

AbstractMicroglia activated after brain injury, are a major source of the pro-inflammatory cytokine interleukin-1 (IL-1), which is known to further exacerbate damage. However, the mechanisms that control IL-1 release in acute neuronal injury are unknown and the purpose of this study was to test the hypothesis that neuronal injury induces IL-1beta release from microglial cells. Here we report that lipopolysaccharide (LPS)-activated rat microglia co-cultured with healthy rat neurons express pro-IL-1beta, which in the absence of cell death accumulates in the cells. Treatment of co-cultures with the excitotoxin N-methyl-D-aspartate (NMDA) induced neuronal cell death leading to the appearance of pro-IL-1beta in the culture supernatant. This effect was reversed by the NMDA receptor antagonist MK-801, and was neuron-dependent, since NMDA had no effect on cell death or pro-IL-1beta release in mixed glial cell cultures. In addition, we show that pro-IL-1beta release from LPS-treated mixed glia or LPS-treated microglia is significantly reduced in the presence of conditioned medium from healthy co-cultures or neuronal cultures respectively. These results demonstrate that injured neurons promote the release of pro-IL-1beta from microglia, possibly by regulating microglial cell viability, and suggest an important alternative mechanism of IL-1beta release that occurs in response to neuronal injury.

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