Immunomodulatory Properties of Sweet Whey-Derived Peptides in THP-1 Macrophages

Sweet whey (SW), a by-product of cheese production, has potential immunomodulatory properties that could be beneficial in preventing inflammation-related diseases. This study investigated the effects of SW derived from bovine, caprine, ovine, or an ovine/caprine mixture of milk on inflammation-relat...

Full description

Saved in:
Bibliographic Details
Main Authors: Eleni Dalaka, Georgios C. Stefos, Ioannis Politis, Georgios Theodorou
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/30/6/1261
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850280322548105216
author Eleni Dalaka
Georgios C. Stefos
Ioannis Politis
Georgios Theodorou
author_facet Eleni Dalaka
Georgios C. Stefos
Ioannis Politis
Georgios Theodorou
author_sort Eleni Dalaka
collection DOAJ
description Sweet whey (SW), a by-product of cheese production, has potential immunomodulatory properties that could be beneficial in preventing inflammation-related diseases. This study investigated the effects of SW derived from bovine, caprine, ovine, or an ovine/caprine mixture of milk on inflammation-related gene expression in THP-1-derived macrophages, both with and without LPS stimulation. Cells were treated with SW-D-P3 (a fraction smaller than 3 kDa produced by in vitro digestion), and the expression of inflammation-related genes was assessed using quantitative PCR. Results showed that the expression of <i>TLR2</i> and <i>ICAM1</i> was attenuated in non-LPS-stimulated macrophages treated with SW-D-P3, regardless of animal origin. Moreover, the expression of <i>TLR4</i>, <i>IL1B,</i> and <i>IL6</i> was decreased and the expression of an NF-κB subunit <i>RELA</i> and <i>CXCL8</i> was elevated in a subset of samples treated with SW-D-P3, depending on the milk source. In LPS-challenged cells, the expression of <i>CXCL8</i> was upregulated and the expression of <i>IRF5</i> and <i>TNFRSF1A</i> was downregulated in SW-D-P3-treated cells, regardless of animal origin. On the other hand, a number of inflammation-related genes were differentially expressed depending on the animal origin of the samples. Moreover, the higher <i>IL10</i> expression observed in cells treated with ovine/caprine SW-D-P3 compared to those treated with SW-D-P3 of bovine, caprine, or ovine origin suggests an anti-inflammatory response, in which alternatively activated macrophages (M2 polarization phenotype) may participate. Overall, these findings suggest that incorporating SW into the food industry, either as a standalone ingredient or supplement, may help to prevent inflammation-related diseases.
format Article
id doaj-art-1a67b2e69bd94be3b69f5d2c8dd4deb1
institution OA Journals
issn 1420-3049
language English
publishDate 2025-03-01
publisher MDPI AG
record_format Article
series Molecules
spelling doaj-art-1a67b2e69bd94be3b69f5d2c8dd4deb12025-08-20T01:48:48ZengMDPI AGMolecules1420-30492025-03-01306126110.3390/molecules30061261Immunomodulatory Properties of Sweet Whey-Derived Peptides in THP-1 MacrophagesEleni Dalaka0Georgios C. Stefos1Ioannis Politis2Georgios Theodorou3Laboratory of Animal Breeding and Husbandry, Department of Animal Science, Agricultural University of Athens, 11855 Athens, GreeceLaboratory of Animal Breeding and Husbandry, Department of Animal Science, Agricultural University of Athens, 11855 Athens, GreeceLaboratory of Animal Breeding and Husbandry, Department of Animal Science, Agricultural University of Athens, 11855 Athens, GreeceLaboratory of Animal Breeding and Husbandry, Department of Animal Science, Agricultural University of Athens, 11855 Athens, GreeceSweet whey (SW), a by-product of cheese production, has potential immunomodulatory properties that could be beneficial in preventing inflammation-related diseases. This study investigated the effects of SW derived from bovine, caprine, ovine, or an ovine/caprine mixture of milk on inflammation-related gene expression in THP-1-derived macrophages, both with and without LPS stimulation. Cells were treated with SW-D-P3 (a fraction smaller than 3 kDa produced by in vitro digestion), and the expression of inflammation-related genes was assessed using quantitative PCR. Results showed that the expression of <i>TLR2</i> and <i>ICAM1</i> was attenuated in non-LPS-stimulated macrophages treated with SW-D-P3, regardless of animal origin. Moreover, the expression of <i>TLR4</i>, <i>IL1B,</i> and <i>IL6</i> was decreased and the expression of an NF-κB subunit <i>RELA</i> and <i>CXCL8</i> was elevated in a subset of samples treated with SW-D-P3, depending on the milk source. In LPS-challenged cells, the expression of <i>CXCL8</i> was upregulated and the expression of <i>IRF5</i> and <i>TNFRSF1A</i> was downregulated in SW-D-P3-treated cells, regardless of animal origin. On the other hand, a number of inflammation-related genes were differentially expressed depending on the animal origin of the samples. Moreover, the higher <i>IL10</i> expression observed in cells treated with ovine/caprine SW-D-P3 compared to those treated with SW-D-P3 of bovine, caprine, or ovine origin suggests an anti-inflammatory response, in which alternatively activated macrophages (M2 polarization phenotype) may participate. Overall, these findings suggest that incorporating SW into the food industry, either as a standalone ingredient or supplement, may help to prevent inflammation-related diseases.https://www.mdpi.com/1420-3049/30/6/1261INFOGESTcheese wheyinflammationqPCR
spellingShingle Eleni Dalaka
Georgios C. Stefos
Ioannis Politis
Georgios Theodorou
Immunomodulatory Properties of Sweet Whey-Derived Peptides in THP-1 Macrophages
Molecules
INFOGEST
cheese whey
inflammation
qPCR
title Immunomodulatory Properties of Sweet Whey-Derived Peptides in THP-1 Macrophages
title_full Immunomodulatory Properties of Sweet Whey-Derived Peptides in THP-1 Macrophages
title_fullStr Immunomodulatory Properties of Sweet Whey-Derived Peptides in THP-1 Macrophages
title_full_unstemmed Immunomodulatory Properties of Sweet Whey-Derived Peptides in THP-1 Macrophages
title_short Immunomodulatory Properties of Sweet Whey-Derived Peptides in THP-1 Macrophages
title_sort immunomodulatory properties of sweet whey derived peptides in thp 1 macrophages
topic INFOGEST
cheese whey
inflammation
qPCR
url https://www.mdpi.com/1420-3049/30/6/1261
work_keys_str_mv AT elenidalaka immunomodulatorypropertiesofsweetwheyderivedpeptidesinthp1macrophages
AT georgioscstefos immunomodulatorypropertiesofsweetwheyderivedpeptidesinthp1macrophages
AT ioannispolitis immunomodulatorypropertiesofsweetwheyderivedpeptidesinthp1macrophages
AT georgiostheodorou immunomodulatorypropertiesofsweetwheyderivedpeptidesinthp1macrophages