Size matters: TLR4-mediated effects of α-(1,5)-linear arabino-oligosaccharides in macrophage-like cells depend on their degree of polymerization.

Linear arabino-oligosaccharides (LAOS) produced from controlled enzymatic hydrolysis of arabinans from sugar beet are well-known because of their chain-length dependent prebiotic effects. However, it is not clear if these α-(1,5)-linked arabinose oligosaccharides can interact directly with immune system cells, as well as if its degree of polymerization (DP) influences possible biological effects. Four high purity LAOS with distinct DP were tested in macrophage-like cells exposed or not to LPS. Results shown that LAOS interact with Toll-like receptor (TLR) 4 in a chain length-dependent manner. LAOS with higher DP induce stimulatory effects mainly through the TLR4/MyD88 pathway, thereby enhancing the release of tumor necrosis factor alpha (TNF-α), interleukin (IL-) 1ß, 6, 12, and chemokines including MCP-1, RANTES, IL-8, and IP-10. Notably, LAOS with lower DP appears to have an opposite effect to those counterparts with higher DP, as they does not induce the secretion of cytokines and chemokines in macrophages-like cells, while also inhibit TLR4-mediated effects induced by both lipopolysaccharide and LAOS with higher DP. These findings provide not only insights into potential biological effects of LAOS, but also reveal that controlled enzymatic hydrolysis of sugar beet arabinans may lead to dietary oligosaccharides with desired biological properties.

Polysaccharides from chayote enhance lipid efflux and regulate NLRP3 inflammasome priming in macrophage-like THP-1 cells exposed to cholesterol crystals.

The contribution of dietary fiber to decrease the risk of atherosclerosis may occur through other mechanisms besides the increased excretion of cholesterol. Although macrophages are crucial for lipid clearance, the excessive uptake of cholesterol crystals (CC) by these cells induce NLRP3 inflammasome and foam cell formation. Thus, we investigated whether the water-soluble DF from chayote (WSP) regulate CC-pretreated macrophage-like THP-1 cells. Linkage analysis indicated that WSP is composed mainly of pectic homogalacturonan and highly branched type I rhamnogalacturonan as well as hemicellulosic material including glucomannan, xyloglucan, and glucurono(arabino)xylan. WSP reduced interleukin (IL)-1ß and chemokine release in CC-pretreated macrophages. Notably, WSP also reduced lipid accumulation in cells previously exposed to CC. Furthermore, WSP upregulated liver X receptor alpha expression, which may account for increased lipid efflux, and reduced matrix metallopeptidase 9 expression. WSP also reduced active caspase-1 protein levels, and downregulated NLRP3 and IL-1ß gene expression in CC-pretreated cells, suggesting that this polysaccharide fraction regulates the priming signals required for NLRP3 inflammasome activation. Thus, WSP regulate lipid efflux and suppress inflammasome priming in macrophages, suggesting that the health benefits of this dietary fiber could go beyond its physical properties on the gastrointestinal tract.

α- and ß-d-Glucans from the edible mushroom Pleurotus albidus differentially regulate lipid-induced inflammation and foam cell formation in human macrophage-like THP-1 cells.

Macrophages play an essential role in lipid metabolism; however, the excessive uptake of modified lipids and cholesterol crystals (CC) leads to the formation of pro-inflammatory lipid-laden macrophages called foam cells. Since the α-1,6- and ß-1,3-d-glucans from the basidiome and the mycelium of the edible mushroom Pleurotus albidus have previously been shown to regulate macrophage function, these glucans were tested in macrophage-like THP-1 cells previously exposed to acetylated low-density lipoproteins (acLDL) or CC. The glucans inhibited lipid-induced inflammation, but only the ß-1,3-d-glucan regulated both the NLRP3 inflammasome activation and the expression of genes involved on lipid efflux in acLDL- or CC-pretreated cells, thereby reducing foam cell formation. In contrast, the two α-1,6-glucans tested inhibited foam cell formation only in acLDL-pretreated cells and had no effect on the expression of the peroxisome proliferator-activated receptor gamma and liver X receptor alpha genes, suggesting that these glucans regulate lipid influx rather than lipid efflux. Thus, α- and ß-d-glucans differentially regulate lipid-induced inflammation and foam cell formation in macrophage-like cells. Furthermore, results emphasize that P. albidus has potential to be used as a functional food or as a source for the extraction of biologically-active glucans.

Characterization and immunomodulatory effects of glucans from Pleurotus albidus, a promising species of mushroom for farming and biomass production.

Polysaccharides from a number of mushroom species are recognized as functional food ingredients with potential health benefits, including immunomodulatory effects. In this study, polysaccharides extracted from the basidiome with cold water (BaCW), hot water (BaHW), and hot alkali (BaHA) solution, and exo- (MyEX) and endopolysaccharides (MyEN) from the submerged culture of Pleurotus albidus, a promising species for farming and biomass production, were analyzed for their chemical composition and structure and immunomodulatory effects on macrophages. Compositional (HPAEC-PAD and HPSEC-RID/MWD) and structural (FT-IR, 1D- and 2D-NMR) analyses identified BaCW and MyEX as ß-(1,6)-branched ß-(1,3)-glucans, BaHW and MyEN as α-(1,3)-(1,2)-branched α-(1,6)-glucans, and BaHA as a mixture of α-(1,6)- and ß-(1,3)-glucans. BaCW and MyEX stimulated the production of tumor necrosis factor alpha (TNF-α) and nitric oxide (NO), but not interleukin-6 (IL-6), and decreased phagocytosis of zymosan particles. In contrast, BaHW and MyEN induced TNF-α, NO and IL-6 production, and increased zymosan phagocytosis, while BaHA displayed intermediary effects in comparison the other polysaccharides. In conclusion, the basidiome and the submerged culture of P. albidus are sources of easily extractable α- and ß-glucans with potential immunomodulatory effects.

The water-soluble non-starch polysaccharides from bananas display immunomodulatory properties on cultured macrophages.

Some diet components, such as certain indigestible polysaccharides from edible plants, may interact with the gut-associated lymphoid tissue and improve the host immune response to pathogens. The non-starch polysaccharides (NSP) from bananas are non-digestible carbohydrates that resemble some immunomodulatory polysaccharides occurring in the cell wall of cereals. Based on this similarity, the effects of the water-soluble NSP from two banana cultivars (Nanicão and Thap Maeo) on the phagocytic activity, nitric oxide (NO) and cytokines produced by cultured macrophages were investigated. An investigation into the monosaccharide composition and the oligomers released by enzymatic hydrolysis of the ultra-filtered fraction above 50kDa and the heat-treated fraction of water-soluble NSP from both cultivars revealed they are mostly composed of mannan and galacturonans (homogalacturonan, xylogalacturonan and rhamnogalacturonan). The NSP tested were able to activate the macrophages, but the effects on the phagocytic activity and the release of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and nitric oxide production were dependent on the polysaccharide concentration and the cultivar origin. Despite some specific differences, the NSP from Nanicão and Thap Maeo banana fruits may be considered prospective food immunomodulators, which contribute to the promotion of a more responsive immune system.