Exogenous l-fucose attenuates neuroinflammation induced by lipopolysaccharide
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved..
α1,6-Fucosyltransferase (Fut8) catalyzes the transfer of fucose to the innermost GlcNAc residue of N-glycan to form core fucosylation. Our previous studies showed that lipopolysaccharide (LPS) treatment highly induced neuroinflammation in Fut8 homozygous KO (Fut8-/-) or heterozygous KO (Fut8+/-) mice, compared with the WT (Fut8+/+) mice. To understand the underlying mechanism, we utilized a sensitive inflammation-monitoring mouse system that contains the human interleukin-6 (hIL6) bacterial artificial chromosome transgene modified with luciferase (Luc) reporter cassette. We successfully detected LPS-induced neuroinflammation in the central nervous system by exploiting this bacterial artificial chromosome transgenic monitoring system. Then we examined the effects of l-fucose on neuroinflammation in the Fut8+/- mice. The lectin blot and mass spectrometry analysis showed that l-fucose preadministration increased the core fucosylation levels in the Fut8+/- mice. Notably, exogenous l-fucose attenuated the LPS-induced IL-6 mRNA and Luc mRNA expression in the cerebral tissues, confirmed using the hIL6-Luc bioluminescence imaging system. The activation of microglial cells, which provoke neuroinflammatory responses upon LPS stimulation, was inhibited by l-fucose preadministration. l-Fucose also suppressed the downstream intracellular signaling of IL-6, such as the phosphorylation levels of JAK2 (Janus kinase 2), Akt (protein kinase B), and STAT3 (signal transducer and activator of transcription 3). l-Fucose administration increased gp130 core fucosylation levels and decreased the association of gp130 with the IL-6 receptor in Fut8+/- mice, which was further confirmed in BV-2 cells. These results indicate that l-fucose administration ameliorates the LPS-induced neuroinflammation in the Fut8+/- mice, suggesting that core fucosylation plays a vital role in anti-inflammation and that l-fucose is a potential prophylactic compound against neuroinflammation.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:300 |
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| Enthalten in: |
The Journal of biological chemistry - 300(2024), 1 vom: 15. Jan., Seite 105513 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Xu, Xing [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 07.02.2024 Date Revised 07.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jbc.2023.105513 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM365334707 |
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| 245 | 1 | 0 | |a Exogenous l-fucose attenuates neuroinflammation induced by lipopolysaccharide |
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| 520 | |a Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a α1,6-Fucosyltransferase (Fut8) catalyzes the transfer of fucose to the innermost GlcNAc residue of N-glycan to form core fucosylation. Our previous studies showed that lipopolysaccharide (LPS) treatment highly induced neuroinflammation in Fut8 homozygous KO (Fut8-/-) or heterozygous KO (Fut8+/-) mice, compared with the WT (Fut8+/+) mice. To understand the underlying mechanism, we utilized a sensitive inflammation-monitoring mouse system that contains the human interleukin-6 (hIL6) bacterial artificial chromosome transgene modified with luciferase (Luc) reporter cassette. We successfully detected LPS-induced neuroinflammation in the central nervous system by exploiting this bacterial artificial chromosome transgenic monitoring system. Then we examined the effects of l-fucose on neuroinflammation in the Fut8+/- mice. The lectin blot and mass spectrometry analysis showed that l-fucose preadministration increased the core fucosylation levels in the Fut8+/- mice. Notably, exogenous l-fucose attenuated the LPS-induced IL-6 mRNA and Luc mRNA expression in the cerebral tissues, confirmed using the hIL6-Luc bioluminescence imaging system. The activation of microglial cells, which provoke neuroinflammatory responses upon LPS stimulation, was inhibited by l-fucose preadministration. l-Fucose also suppressed the downstream intracellular signaling of IL-6, such as the phosphorylation levels of JAK2 (Janus kinase 2), Akt (protein kinase B), and STAT3 (signal transducer and activator of transcription 3). l-Fucose administration increased gp130 core fucosylation levels and decreased the association of gp130 with the IL-6 receptor in Fut8+/- mice, which was further confirmed in BV-2 cells. These results indicate that l-fucose administration ameliorates the LPS-induced neuroinflammation in the Fut8+/- mice, suggesting that core fucosylation plays a vital role in anti-inflammation and that l-fucose is a potential prophylactic compound against neuroinflammation | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a N-glycosylation | |
| 650 | 4 | |a core fucosylation | |
| 650 | 4 | |a interleukin-6 | |
| 650 | 4 | |a microglia | |
| 650 | 4 | |a neuroinflammation | |
| 650 | 7 | |a Cytokine Receptor gp130 |2 NLM | |
| 650 | 7 | |a 133483-10-0 |2 NLM | |
| 650 | 7 | |a Fucose |2 NLM | |
| 650 | 7 | |a 28RYY2IV3F |2 NLM | |
| 650 | 7 | |a Fucosyltransferases |2 NLM | |
| 650 | 7 | |a EC 2.4.1.- |2 NLM | |
| 650 | 7 | |a Interleukin-6 |2 NLM | |
| 650 | 7 | |a Lipopolysaccharides |2 NLM | |
| 650 | 7 | |a RNA, Messenger |2 NLM | |
| 700 | 1 | |a Fukuda, Tomohiko |e verfasserin |4 aut | |
| 700 | 1 | |a Takai, Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Morii, Sayaka |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Yuhan |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Jianwei |e verfasserin |4 aut | |
| 700 | 1 | |a Ohno, Shiho |e verfasserin |4 aut | |
| 700 | 1 | |a Isaji, Tomoya |e verfasserin |4 aut | |
| 700 | 1 | |a Yamaguchi, Yoshiki |e verfasserin |4 aut | |
| 700 | 1 | |a Nakano, Miyako |e verfasserin |4 aut | |
| 700 | 1 | |a Moriguchi, Takashi |e verfasserin |4 aut | |
| 700 | 1 | |a Gu, Jianguo |e verfasserin |4 aut | |
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