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-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 TLR2 and ICAM1 was attenuated in non-LPS-stimulated macrophages treated with SW-D-P3, regardless of animal origin. Moreover, the expression of TLR4, IL1B, and IL6 was decreased and the expression of an NF-κB subunit RELA and CXCL8 was elevated in a subset of samples treated with SW-D-P3, depending on the milk source. In LPS-challenged cells, the expression of CXCL8 was upregulated and the expression of IRF5 and TNFRSF1A 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 IL10 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.