Neuroprotection by IFN- via astrocyte-secreted IL-6 in acute neuroinflammation.
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Inflammation eliminates pathogenic infections while also threatening the integrity of the central nervous system. In this study, using in vivo and in vitro models of acute neuroinflammation, we investigated the mechanisms by which inflammation and astrocytes affect neuronal apoptosis. The in vitro model mimicked acute neuroinflammation by incubation in IFN--containing media with primary cultured cerebellar granule neurons, with or without cultured astrocytes. This quickly induced neuronal apoptosis characterized by cleaved caspase-3 expression, Hoechst 33342 staining, and intercellular Ca2+ influx, whereas the presence of astrocytes significantly protected neurons from these effects. IFN- in the inflammation media also promoted astrocyte secretion of IL-6, essential for protection. The supernatants of rat peripheral blood mononuclear cells stimulated by lymphocyte mitogen lipopolysaccharide or concanavalin A were used as inflammation media to verify the results. The in vivo model involved a peripheral challenge with lipopolysaccharide, with or without recombinant IFN-, in C57BL/6 mice. This confirmed the in vitro results: anti-IFN- antibodies exacerbated the acute course of neuroinflammation and led to neurocyte apoptosis in vivo. The pro-inflammatory cytokine IFN- provided neuroprotection during acute neuroinflammation via induction of astrocyte-secreted IL-6. The findings provide novel insights into the mechanisms of neuroprotection by IFN- during acute neuroinflammation, and may impact therapies for inflammation-related central nervous system injury and disease.
author list (cited authors)
Sun, L., Li, Y., Jia, X., Wang, Q. i., Li, Y., Hu, M., ... Ren, H.
complete list of authors
Sun, Lijie||Li, Yan||Jia, Xiuzhi||Wang, Qi||Li, Yue||Hu, Minghui||Tian, Linlu||Yang, Jinfeng||Xing, Wenjing||Zhang, Weihua||Wang, Jingtao||Xu, Hongwei||Wang, Lihua||Zhang, Dekai||Ren, Huan