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Toll-like receptor mediated activation is possibly involved in immunoregulating properties of cow's milk hydrolysates.

ABSTRACT: Immunomodulating proteins and peptides are formed during the hydrolysis of cow's milk proteins. These proteins are potential ingredients in functional foods used for the management of a range of immune related problems, both in infants and adults. However, the mechanism behind these effects is unknown. We hypothesize that the interaction of peptides with Toll-like receptors (TLRs) can induce immune effects, since these receptors are known to sample many dietary molecules in the intestine in order to regulate immune effects. To investigate this, we compared the immune effects and TLR activation and inhibition by whey and casein hydrolysates with different hydrolysis levels. We first measured cytokine production in primary peripheral blood mononuclear cells stimulated with either whey, casein, or their hydrolysates. IL-10 and TNF? were induced by whey hydrolysates (decreasing with increasing hydrolysis level), but not by casein hydrolysates. Next, the activation of TLR 2, 3, 5 and 9 receptors were observed by intact and mildly hydrolysed whey proteins only and not by casein hydrolysates in TLR reporter cell lines. Many casein hydrolysates inhibited TLR signaling (mainly TLR 5 and 9). These results demonstrate that the effects of cow's milk proteins on the immune system are protein type and hydrolysis dependent. TLR signaling is suggested as a possible mechanism for differences in effect. This knowledge contributes to a better understanding of the immune effects of hydrolysates and the design of infant formula, and nutrition in general, with specific immunoregulatory effects.

SUBMITTER: Kiewiet MBG

PROVIDER: S-EPMC5464564 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Toll-like receptor mediated activation is possibly involved in immunoregulating properties of cow's milk hydrolysates.

Kiewiet M B Gea MBG Dekkers Renske R Gros Marjan M van Neerven R J Joost RJJ Groeneveld Andre A de Vos Paul P Faas Marijke M MM

PloS one 20170608 6

Immunomodulating proteins and peptides are formed during the hydrolysis of cow's milk proteins. These proteins are potential ingredients in functional foods used for the management of a range of immune related problems, both in infants and adults. However, the mechanism behind these effects is unknown. We hypothesize that the interaction of peptides with Toll-like receptors (TLRs) can induce immune effects, since these receptors are known to sample many dietary molecules in the intestine in orde ...[more]

PMID: 28594834

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Project description:SUMMARY Research background Milk protein hydrolysates have received particular attention due to their health-promoting effects. Dromedary milk differs from the milk of other dairy animals in the composition and structure of its protein components, which give it unique properties. The bioactivity and functionality of whole dromedary milk proteins and their enzymatic hydrolysates have not received much attention, hence this study aims to investigate the effect of enzymatic hydrolysis of dromedary milk proteins on their antioxidant activities and functional properties. Experimental approach Dromedary milk proteins were treated using four proteolytic enzymes (pepsin, trypsin, ?-chymotrypsin and papain) and two mixtures of enzymes (pancreatin and pronase). The degree of hydrolysis was measured to verify the hydrolysis of the proteins. The sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and gel filtration chromatography served to determine the molecular mass distribution of the hydrolysates while reversed phase-high performance liquid chromatography (RP-HPLC) was conducted to explore their hydrophobicity. The antioxidant activities were evaluated using various in vitro tests, including 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging capacities, iron(III) reducing ability and chelating activity. Besides, functional properties such as solubility, foaming and emulsification were assessed. Results and conclusions Dromedary milk protein hydrolysates exhibited different degrees of hydrolysis ranging from 17.69 to 41.86%. Apart from that, the hydrolysates showed different electrophoretic patterns, molecular mass distribution and RP-HPLC profiles demonstrating the heterogeneity of the resulting peptides in terms of molecular mass and polarity. The hydrolysates displayed significantly higher antioxidant capacities than the undigested proteins at all the tested concentrations. Iron(II) chelating activity was the most improved assay after proteolysis and the hydrolysate generated with pancreatin had the highest chelating power. Dromedary milk protein hydrolysates possessed good solubility (>89%). Further, foaming and emulsifying properties of dromedary milk proteins were enhanced after their proteolysis. These interfacial properties were influenced by the enzymes employed during proteolysis. Novelty and scientific contribution Enzymatic hydrolysis of dromedary milk proteins is an effective tool to obtain protein hydrolysates with great antioxidant and functional properties. These results suggest that dromedary milk protein hydrolysates could be used as a natural source of antioxidant peptides to formulate functional foods and nutraceuticals.

Project description:BackgroundCurrent guidelines emphasize early introduction to potentially allergenic foods, but the optimal timing, amount, and exposure routes for foods other than peanut are not well-established. Cow's milk is often the first allergenic food introduced through infant formulas.ObjectiveTo examine timing of cow's milk protein introduction (CMPI), including interaction with formula supplementation after delivery, in relation to reported cow's milk adverse reactions throughout childhood.MethodsAmong children in the Boston, Mass-area Project Viva cohort, we assessed timing of CMPI (<2 weeks, 2 weeks-<6 months, ≥6 months) with questionnaires administered in infancy. Outcomes were (1) parent-reported cow's milk adverse reactions via annual questionnaires from age 2 to 13 years (n = 1298) and (2) milk sensitization (n = 505) and IgE-mediated milk allergy (n = 491) at age approximately 8 years. We used multivariable logistic regression models adjusted for parental atopy history, delivery mode, gestational age at delivery, child race, and census tract median household income, and investigated effect modification by ever/never breast-fed status and formula supplementation in the delivery hospital.ResultsA total of 32% were introduced to cow's milk protein at age less than 2 weeks, 38% at age 2 weeks to less than 6 months, and 30% at age 6 months or more. Compared with children with CMPI at age less than 2 weeks, children with CMPI at age 6 months or more had a higher risk of cow's milk adverse reaction at age 2 to 5 years (odds ratio, 2.4 [1.2-4.7]). Children given formula after delivery + CMPI at age less than 2 weeks had the lowest risk overall. Among children not given formula after delivery, CMPI at age 2 weeks to 6 months appeared most protective. Results were similar among ever-breast-fed children. Timing of CMPI was not associated with milk sensitization or IgE-mediated milk allergy in mid-childhood.ConclusionsEarly, consistent cow's milk exposure appears protective against adverse reactions to cow's milk.

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Toll-like receptor mediated activation is possibly involved in immunoregulating properties of cow's milk hydrolysates.

Publications

Toll-like receptor mediated activation is possibly involved in immunoregulating properties of cow's milk hydrolysates.

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