ArticleScientific reports2017
Identification and activation of TLR4-mediated signalling pathways by alginate-derived guluronate oligosaccharide in RAW264.7 macrophages.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed, 196 citations in OpenAlex.
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- Effect of Bean-Derived Soluble Dietary Fibers on Macrophage Function In Vitro.Foods (Basel, Switzerland) · 2026Article
- Alginate oligosaccharides derived from tropical brown seaweeds as sustainable alternatives to antibiotic growth promoters in poultry nutrition: Functional mechanisms and production perspectives.Veterinary world · 2026Review
- Emerging neuroprotective mechanisms and therapeutic potential of natural polysaccharides in Alzheimer's disease.Frontiers in aging neuroscience · 2026Review
- Effects of two kinds of marine algae polysaccharides and their oligosaccharides on lipid metabolism and gut microbiota in high-fat diet mice.Microbiology spectrum · 2025Article
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- Antibacterial and Immunosuppressive Effects of a Novel Marine Brown Alga-Derived Ester in Atopic Dermatitis.Marine drugs · 2024Article
- Mesenchymal Stem Cell-Derived Exosomes as Drug Carriers for Delivering miRNA-29b to Ameliorate Inflammation in Corneal Injury Via Activating Autophagy.Investigative ophthalmology & visual science · 2024Article
- Bioarchitectural Design of Bioactive Biopolymers: Structure-Function Paradigm for Diabetic Wound Healing.Biomimetics (Basel, Switzerland) · 2024Review
20 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alginate, 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.
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Registered trials
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