{"title":"Methyl-esterification, degree of polymerization and ∆4,5-unsaturation of galacturonic acid oligosaccharides as determinants of immunomodulation","authors":"J.W. Zwolschen , M.M.M. Tomassen , A.P. Vos , H.A. Schols","doi":"10.1016/j.carbpol.2024.123052","DOIUrl":null,"url":null,"abstract":"<div><div>In recent years, immunomodulation by pectin and pectin-derived galacturonic acid oligosaccharides has been the subject of wide-spread scientific research due to the potential of different pectin structures as bioactive biomolecules. Yet, gaps remain in understanding the structure-dependent immunomodulation of galacturonic acid. This study describes <em>in vitro</em> immunomodulatory effects of well-characterized galacturonic acid oligosaccharides. Both methyl-esterified and non-methyl-esterified galacturonic acid oligosaccharides with a saturated non-reducing end (degree of polymerization 1–10) significantly induced cytokine production by THP-1 macrophages and directly activated TLR2 and TLR4 in transfected HEK-293 cells, even when accounting for minor endotoxin contamination. In contrast, both methyl-esterified and non-methyl-esterified galacturonic acid oligosaccharides with a Δ4,5-unsaturated non-reducing end (degree of polymerization 1–7) did not activate TLR2 and TLR4 and led to significantly reduced cytokine production (<em>p</em> < 0.05), suggesting Δ4,5-(un)saturation as a pivotal factor for immunomodulation by galacturonic acid oligosaccharides. Exposure to non-methyl-esterified saturated galacturonic acid oligosaccharides resulted in significantly lower TNF-α production, IL-1β production and TLR4 activation (<em>p</em> < 0.05) compared to methyl-esterified saturated galacturonic acid oligosaccharides, while IL-10 production and TLR2 activation remained unchanged. These findings establish galacturonic acid oligosaccharides as versatile immunomodulators with TLR2 and TLR4 binding capacity, fit for different immunomodulatory applications depending on their structural characteristics.</div></div>","PeriodicalId":261,"journal":{"name":"Carbohydrate Polymers","volume":"350 ","pages":"Article 123052"},"PeriodicalIF":10.7000,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Carbohydrate Polymers","FirstCategoryId":"92","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0144861724012785","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, APPLIED","Score":null,"Total":0}
引用次数: 0
Abstract
In recent years, immunomodulation by pectin and pectin-derived galacturonic acid oligosaccharides has been the subject of wide-spread scientific research due to the potential of different pectin structures as bioactive biomolecules. Yet, gaps remain in understanding the structure-dependent immunomodulation of galacturonic acid. This study describes in vitro immunomodulatory effects of well-characterized galacturonic acid oligosaccharides. Both methyl-esterified and non-methyl-esterified galacturonic acid oligosaccharides with a saturated non-reducing end (degree of polymerization 1–10) significantly induced cytokine production by THP-1 macrophages and directly activated TLR2 and TLR4 in transfected HEK-293 cells, even when accounting for minor endotoxin contamination. In contrast, both methyl-esterified and non-methyl-esterified galacturonic acid oligosaccharides with a Δ4,5-unsaturated non-reducing end (degree of polymerization 1–7) did not activate TLR2 and TLR4 and led to significantly reduced cytokine production (p < 0.05), suggesting Δ4,5-(un)saturation as a pivotal factor for immunomodulation by galacturonic acid oligosaccharides. Exposure to non-methyl-esterified saturated galacturonic acid oligosaccharides resulted in significantly lower TNF-α production, IL-1β production and TLR4 activation (p < 0.05) compared to methyl-esterified saturated galacturonic acid oligosaccharides, while IL-10 production and TLR2 activation remained unchanged. These findings establish galacturonic acid oligosaccharides as versatile immunomodulators with TLR2 and TLR4 binding capacity, fit for different immunomodulatory applications depending on their structural characteristics.
期刊介绍:
Carbohydrate Polymers stands as a prominent journal in the glycoscience field, dedicated to exploring and harnessing the potential of polysaccharides with applications spanning bioenergy, bioplastics, biomaterials, biorefining, chemistry, drug delivery, food, health, nanotechnology, packaging, paper, pharmaceuticals, medicine, oil recovery, textiles, tissue engineering, wood, and various aspects of glycoscience.
The journal emphasizes the central role of well-characterized carbohydrate polymers, highlighting their significance as the primary focus rather than a peripheral topic. Each paper must prominently feature at least one named carbohydrate polymer, evident in both citation and title, with a commitment to innovative research that advances scientific knowledge.