Identification and Activation of TLR4-mediated Signalling Pathways by Alginate-derived Guluronate Oligosaccharide in RAW264.7 Macrophages

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aut.relation.issue1en_NZ
aut.relation.journalScientific Reportsen_NZ
aut.relation.volume7en_NZ
aut.researcherLu, Jun
dc.contributor.authorFang, Wen_NZ
dc.contributor.authorBi, Den_NZ
dc.contributor.authorZheng, Ren_NZ
dc.contributor.authorCai, Nen_NZ
dc.contributor.authorXu, Hen_NZ
dc.contributor.authorZhou, Ren_NZ
dc.contributor.authorLu, Jen_NZ
dc.contributor.authorWan, Men_NZ
dc.contributor.authorXu, Xen_NZ
dc.date.accessioned2017-07-21T04:01:36Z
dc.date.available2017-07-21T04:01:36Z
dc.date.copyright2017-12-01en_NZ
dc.date.issued2017-12-01en_NZ
dc.description.abstractAlginate, a natural acidic polysaccharide extracted from marine brown seaweeds, is composed of different blocks of β-(1, 4)-D-mannuronate (M) and its C-5 epimer α-(1, 4)-L-guluronate (G). Alginate-derived guluronate oligosaccharide (GOS) readily activates macrophages. However, to understand its role in immune responses, further studies are needed to characterize GOS transport and signalling. Our results show that GOS is recognized by and upregulates Toll-like receptor 4 (TLR4) on RAW264.7 macrophages, followed by its endocytosis via TLR4. Increased expression of TLR4 and myeloid differentiation protein 2 (MD2) results in Akt phosphorylation and subsequent activation of both nuclear factor-κB (NF-κB) and mechanistic target of rapamycin (mTOR). Moreover, GOS stimulates mitogen-activated protein kinases (MAPKs); notably, c-Jun N-terminal kinase (JNK) phosphorylation depends on TLR4 initiation. All these events contribute to the production of inflammatory mediators, either together or separately. Our findings also reveal that GOS induces cytoskeleton remodelling in RAW264.7 cells and promotes macrophage proliferation in mice ascites, both of which improve innate immunity. Conclusively, our investigation demonstrates that GOS, which is dependent on TLR4, is taken up by macrophages and stimulates TLR4/Akt/NF-κB, TLR4/Akt/mTOR and MAPK signalling pathways and exerts impressive immuno-stimulatory activity.en_NZ
dc.identifier.citationScientific Reports, 7(1), 1663.
dc.identifier.doi10.1038/s41598-017-01868-0en_NZ
dc.identifier.issn2045-2322en_NZ
dc.identifier.urihttps://hdl.handle.net/10292/10666
dc.publisherMacmillan Publishers Limited
dc.relation.urihttps://www.nature.com/articles/s41598-017-01868-0
dc.rightsThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
dc.rights.accessrightsOpenAccessen_NZ
dc.subjectGlycobiology; Polysaccharides
dc.titleIdentification and Activation of TLR4-mediated Signalling Pathways by Alginate-derived Guluronate Oligosaccharide in RAW264.7 Macrophagesen_NZ
dc.typeJournal Article
pubs.elements-id280476
pubs.organisational-data/AUT
pubs.organisational-data/AUT/Health & Environmental Science
pubs.organisational-data/AUT/Health & Environmental Science/Interprofessional Health
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