[No authors listed]
BACKGROUND:α1,6-Fucosyltransferase-deficient (Fut8-/-) mice displayed increased locomotion and schizophrenia-like behaviors. Since neuroinflammation is a common pathological change in most brain diseases, this study was focused on investigating the effects of Fut8 in microglia and astrocytes. METHODS:Brain tissues were analyzed using immunohistochemical staining. Core fucosylation and protein expression were analyzed using lectin blot and western blot, respectively. Fut8-knockout (KO) cells were established by the CRISPR/Cas9 system. RESULTS:The number of Iba-1 positive cells and GFAP positive cells were significantly increased in both untreated and lipopolysaccharide stimulated inflammatory conditional Fut8-/- mice by comparison with both wild-type (Fut8+/+) and hetero (Fut8+/-) mice. Stimulation with pro-inflammatory factors, such as IFN-γ and IL-6, induced expression levels of fucosylation in primary microglia and astrocytes, as well as in glial cell lines. Cell motility and iNOS expression were easily induced by IFN-γ in Fut8-KO BV-2 cells compared with wild-type (WT) cells. In a similar manner, both Fut8-KO C6 cells and primary astrocytes treated with 2-fluoro-L-fucose, a specific inhibitor for fucosylation, showed a higher response to IL-6-stimulated signaling, compared with WT cells. CONCLUSIONS:Core fucosylation negatively regulates the states of neuroinflammation by modulating the sensitivity of microglia and astrocytes to inflammatory mediators. The disorders of Fut8-/- mice are caused not only by neurons but also by glial cell dysfunction. GENERAL SIGNIFICANCE:Core fucose is a novel regulator for neuroinflammation in the central nervous system.
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