The Impacts of Cholesterol, Oxysterols, and Cholesterol Lowering Dietary Compounds on the Immune System

Abstract

Cholesterol and its oxidized forms, oxysterols, are ingested from foods and are synthesized de novo. Cholesterol and oxysterols influence molecular and cellular events and subsequent biological responses of immune cells. The amount of dietary cholesterol influence on the levels of LDL cholesterol and blood oxysterols plays a significant role in the induction of pro-inflammatory state in immune cells, leading to inflammatory disorders, including cardiovascular disease. Cholesterol and oxysterols synthesized de novo in immune cells and stroma cells are involved in immune homeostasis, which may also be influenced by an excess intake of dietary cholesterol. Dietary compounds such as β-glucan, plant sterols/stanols, omega-3 lipids, polyphenols, and soy proteins, could lower blood cholesterol levels by interfering with cholesterol absorption and metabolism. Such dietary compounds also have potential to exert immune modulation through diverse mechanisms. This review addresses current knowledge about the impact of dietary-derived and de novo synthesized cholesterol and oxysterols on the immune system. Possible immunomodulatory mechanisms elicited by cholesterol-lowering dietary compounds are also discussed.

Effects of camelina oil supplementation on lipid profile and glycemic control: a systematic review and dose‒response meta-analysis of randomized clinical trials

“…According to the subgroup results, TC decreased in doses of less than 30 g/d and intervention durations of more than 8 weeks. It is plausible that COS higher than 30 g/d can lead to an increase in the percentage of energy intake, as a previous study demonstrated that ALA intake higher than eight g/d increased energy intake and consequently increased the risk of metabolic syndrome [ 47 , 48 ].…”

Cholesterol‐autoxidation metabolites in host defense against infectious diseases

“…At high cholesterol levels, the conformational change of SCAP allows itself to interact with insulininduced gene 1 protein (INSIG1) directly and form SCAP/INSIG1 complex, which remains on the endoplasmic reticulum (ER) membrane in an inactive state [37]. At this time, 25-OHC can bind to SREBP-2 and then target either SCAP or INSIG1 to form SREBP-2/SCAP/INSIG1 complex [38]. The formation of SREBP-2/SCAP/INSIG1 complex in mice is dependent on the embedment of 25-OHC into the molecular structure of SCAP/INSIG1 complex and inhibits the transcriptional activity of SREBP-2 and inflammasome assembly [38,39].…”

“…At this time, 25-OHC can bind to SREBP-2 and then target either SCAP or INSIG1 to form SREBP-2/SCAP/INSIG1 complex [38]. The formation of SREBP-2/SCAP/INSIG1 complex in mice is dependent on the embedment of 25-OHC into the molecular structure of SCAP/INSIG1 complex and inhibits the transcriptional activity of SREBP-2 and inflammasome assembly [38,39]. Furthermore, 25-OHC produced in the LPS-activated mouse MUs is able to successively suppress SREBP-2 activation, cholesterol synthesis, AIM2 inflammasome activity, IL-1β release, and inflammation [33,35,36,[38][39][40].…”

“…The formation of SREBP-2/SCAP/INSIG1 complex in mice is dependent on the embedment of 25-OHC into the molecular structure of SCAP/INSIG1 complex and inhibits the transcriptional activity of SREBP-2 and inflammasome assembly [38,39]. Furthermore, 25-OHC produced in the LPS-activated mouse MUs is able to successively suppress SREBP-2 activation, cholesterol synthesis, AIM2 inflammasome activity, IL-1β release, and inflammation [33,35,36,[38][39][40]. It is worth mentioning that 25-OHC-reduced SREBP-2 level in mice affects plasma cell and IgA differentiation by restricting cholesterol biosynthesis in B cells, which also provides strong evidence for the relationship between 25-OHC and SREBP-2 [41].…”

“…A recent study has revealed that 5,6-EC can activate the cysteinyl aspartate specific proteinase-3/7 (caspase-3/7)mediated apoptotic pathway by inducing mitochondrial membrane potential changes to produce ROS, which ultimately leads to apoptosis in human osteoma cells [116]. It is worthwhile to Produced by MU activation of TLR in response to pathogen invasion and has extensive antiviral activity [28,29] Regulates plasma cell/IgA production [7,41] Regulates the activation of inflammatory bodies by affecting the level of SREBP-2 [35][36][37][38][39] Acts as a ligand to activate nuclear receptors to regulate inflammatory damage after infection [62,63] Mediates the remodeling of cholesterol in the plasma membrane and limits the intracellular transmission of LM and Shigella fowleri Prevents cell damage caused by CDCs [92,98] 7-hydroxycholesterol (7-OHC)…”