| First Author | Lu X | Year | 2019 |
| Journal | Biochim Biophys Acta Gen Subj | Volume | 1863 |
| Issue | 3 | Pages | 598-608 |
| PubMed ID | 30572004 | Mgi Jnum | J:270664 |
| Mgi Id | MGI:6277556 | Doi | 10.1016/j.bbagen.2018.12.008 |
| Citation | Lu X, et al. (2019) Deficiency of alpha1,6-fucosyltransferase promotes neuroinflammation by increasing the sensitivity of glial cells to inflammatory mediators. Biochim Biophys Acta Gen Subj 1863(3):598-608 |
| abstractText | BACKGROUND: alpha1,6-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-gamma 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-gamma 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 phospho-STAT3 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. |
