Lipids derived from Camel milk regulate NLRP3 inflammasome-dependent inflammatory responses in human macrophages

Abstract

Background: Camel milk is widely used for its reported anti-diabetic and health promoting effects. Lipids derived from the milk have also been shown to exhibit potent anti-inflammatory effects. The mechanism through which these lipids and constituent fatty acids exert these effects remains elusive. The aim of this study was to investigate the effect of camel milk on glycated protein-mediated macrophage inflammation.Methods: To determine the effect of Total Lipids (TL) and Total Fatty Acids (TFA) derived from camel milk on an in vitro model of diabetic inflammation, differentiated THP-1 (dTHP-1) cells stimulated with glycated serum albumin (gBSA) was employed. Cells were pre-treated with TL or TFA before challenging cells with gBSA.Results: Gas Chromatography-Mass Spectrometry (GC-MS) analysis found that TL was 96% triacylglycerol (TAG) while the TFA comprised 65% saturated and 35% unsaturated fatty acids. Both TL and TFA significantly (p<0.05) decreased gBSA-induced secretion of pro-inflammatory cytokines (Tumour necrosis factor-(TNF)-α, Interleukin-(IL)-1β/18). TL also demonstrated the ability to regulate the expression of p50/p65 sub-units of Nuclear Factor-kappa B (NF-κB), while concomitantly increasing the expression of regulatory cytokines IL-10, IL-1 Receptor Antagonist (IL-1Ra) and Cluster of Differentiation 163 (CD163)-shifting cells towards an M2 macrophage phenotype. Additionally, we found that TL significantly regulated the expression of Nucleotide-binding oligomerization domain-like receptor family pyrin domain containing-3 (NLRP3) inflammasome subunit and its regulator; Ten-Eleven Translocation-2 (TET-2).Conclusion: This paper demonstrates the ability of camel milk lipids to regulate gBSA-induced macrophage inflammation in vitro, by modulating the expression of key inflammatory regulators such NF-kB and NLRP3 inflammasome subunit. Keywords: Camel milk lipids, Macrophages, NF-kB, NLRP3-inflammasome, TET-2