Plant-Derived Phytosterols as Membrane Regulators of Inflammatory Signalling

Phytosterols are plant-derived sterols that are structurally similar to cholesterol and have been extensively studied for their biological roles in lipid metabolism. Emerging evidence also suggests that they may have an effect on inflammatory responses. Here, we focus on the membrane-related functions of phytosterols, with specific emphasis on how structural differences modify membrane organization and physical properties, and thereby influence inflammatory activities. In model membranes, stigmasterol, campesterol and β-sitosterol exhibit different effects on lipid packing, membrane order and physical properties in a structure-dependent manner. However, there is limited evidence that these changes are associated with inflammatory signalling. The key molecular evidence implies a relationship exists between p67 phox recruitment, NADPH oxidase activity, reactive oxygen species production and NLRP3-related responses, and PS-associated modifications in membrane lipid packing. Other cellular studies demonstrate alterations in prostaglandin release and inflammatory signalling, but lack biophysical properties of the membrane. Furthermore, phytosterol effects are not invariably anti-inflammatory and depend on the kind of sterol and the experimental conditions. Phytosterols may also modulate intracellular pathways linking inflammatory responses with cellular lipid homeostasis, such as LXR/ABCA1 and MAPK signalling. The extent to which membrane remodelling contributes to these effects is unknown, and further investigation is required to determine whether the proposed mechanism applies to other phytosterols and experimental models. Further studies are needed, particularly with the incorporation of phytosterols into immune-cell membranes in vivo and the relative contributions of membrane effects and downstream metabolic processes.