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 <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.