Abstract
Immunomodulatory nutraceuticals have garnered special attention due to their therapeutic potential for the amelioration of many chronic inflammatory conditions. Macrophages are key players in the induction, propagation and resolution of inflammation, actively contributing to the pathogenesis and resolution of inflammatory disorders. As such, this study aimed to investigate the possible therapeutic effects bovine casein derived nutraceuticals exert on macrophage immunological function. Initial studies demonstrated that sodium caseinate induced a M2-like macrophage phenotype that was attributed to the kappa-casein subunit. Kappa-casein primed macrophages acquired a M2-like phenotype that expressed CD206, CD54, OX40L, CD40 on the cell surface and gene expression of Arg-1, RELM-α and YM1, archetypical M2 markers. Macrophages stimulated with kappa-casein secreted significantly reduced TNF-α and IL-10 in response to TLR stimulation through a mechanism that targeted the nuclear factor-κB signal transduction pathway. Macrophage proteolytic processing of kappa-casein was required to elicit these suppressive effects, indicating that a fragment other than C-terminal fragment, glycomacropeptide, induced these modulatory effects. Kappa-casein treated macrophages also impaired T-cell responses. Given the powerful immuno-modulatory effects exhibited by kappa-casein and our understanding of immunopathology associated with inflammatory diseases, this fragment has the potential as an oral nutraceutical and therefore warrants further investigation.
Highlights
Nutraceutical is a term derived from “nutrition” and “pharmaceutical” that is applied to products that are isolated from herbal, dietary supplements and functional foods such as dairy, cereals and beverages which, beyond nutritional value, possess physiological benefits to improve health or prevent chronic diseases [1,2]
We further examined the effect that NaCAS exerts on macrophages by investigating any influence CAS has on macrophage phenotypes, which can acquire either a classically activated M1 or an alternatively
Having observed κ-CAS capacity to modulate murine macrophage phenotypes, cytokine responses and T-cell priming capabilities, we examined if these effects were transferable to humans using human monocyte derived macrophages
Summary
Nutraceutical is a term derived from “nutrition” and “pharmaceutical” that is applied to products that are isolated from herbal, dietary supplements and functional foods such as dairy, cereals and beverages which, beyond nutritional value, possess physiological benefits to improve health or prevent chronic diseases [1,2]. In particular, has a great potential to be used commercially as a source of nutraceuticals, as the production and consumption of milk products has increased [3] and the proteins and peptides derived from milk have already been shown to display an array of bioactive properties, including anti-tumour, anti-microbial, anti-oxidant, opioid, ACE-inhibitory and immune-modulatory activity [4,5,6]. The most frequently used strategies involves the use of drugs that slow the progression of specific diseases, they can often have unforeseen and potentially harmful side effects which can outweigh their benefits [8]. In this context, immune modulation via dietary supplementation with bioactive nutraceuticals may represent a viable alternative as they display
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