Macrophage-Immunomodulatory Actions of Bovine Whey Protein Isolate, Glycomacropeptide, and Their In Vitro and In Vivo Digests

Abstract

Whey protein isolate (WPI) consists of an array of proteins and peptides obtained as a byproduct of the cheesemaking process. Research suggests that WPI, along with its peptides such as glycomacropeptide (GMP), possesses immunomodulatory properties. These properties hold potential for alleviating the adverse effects of inflammatory conditions such as inflammatory bowel disease. Although promising, the immunoregulatory properties of the digested forms of WPI and GMP—those most likely to interact with the gut immune system—remain under-investigated. To address this knowledge gap, the current study examined the effects of in vitro-digested WPI and GMP, in vivo-digested WPI, and undigested WPI and GMP on the secretion of pro-inflammatory cytokines (TNF-α and IL-1β) in lipopolysaccharide-stimulated macrophage-like cells. Our results indicate that digested WPI and GMP reduced the expression of TNF-α and IL-1β, two pro-inflammatory cytokines. Whole WPI had no effect on TNF-α but reduced IL-1β levels. In contrast, in vivo-digested WPI reduced TNF-α but increased IL-1β. Undigested GMP, on the other hand, increased the secretion of both cytokines. These results demonstrate that digestion greatly modifies the effects of WPI and GMP on macrophages and suggest that digested WPI and GMP could help mitigate gastrointestinal inflammation. Further clinical studies are necessary to determine the biological relevance of WPI and GMP digestion products within the gut and their capacity to influence gut inflammation.

CSN1S1, CSN3 and LPL: Three Validated Gene Polymorphisms Useful for More Sustainable Dairy Production in the Mediterranean River Buffalo

“…Therefore, it is possible that the κ-casein has retained some of the functions of its ancestral gene and plays an active role as indicator of SCS and mastitis. Further support for this statement derives from the role that the κ-casein glycomacropeptide (GMP) plays in modulating the immune response, and its antibacterial and anti-inflammatory properties [48][49][50]. In addition, SNP rs43703017, located in CSN3, has recently been associated with an increase in SCS in domestic cattle [51].…”

Glycomacropeptide: A comprehensive understanding of its major biological characteristics and purification methodologies

“…The approximate molecular mass of non-glycosylated GMP monomers ranges between 6.8 and 8.0 kDa, whereas the average molecular mass of glycosylated GMP increases to 9.5 kDa due to glycosylation (Córdova-Dávalos et al, 2019). Over the last decade, extensive research has been conducted on the biological activities of GMP, revealing its prebiotic (Montanari et al, 2022), anti-oxidative, anti-inflammatory (Córdova-Dávalos et al, 2023), and immunoregulatory properties (Olsen et al, 2023). GMP has shown the ability to regulate important body systems, such as the gastrointestinal system, endocrine system, and immune system, both in vitro and in vivo (Córdova-Dávalos et al, 2019).…”

“…Furthermore, it demonstrates structural stability even under heat exposure. These distinctive characteristics, coupled with its diverse range of bioactivities and emulsifying properties, suggest the high potential of GMP to be widely used in the food industry (Olsen et al, 2023). Furthermore, GMP has an excellent safety record without causing immunogenic effects, which was reported by Mikkelsen et al (2006) and cited by Muñoz et al (2017), indicating its potential as an ingredient in functional foods (Akın, 2015;Korhonen, 2011).…”