The Modulatory Effect of Lipoproteins on the Release of Interleukin 1 by Human Peritoneal Macrophages Stimulated with β‐1,3‐d‐Polyglucose Derivatives

Abstract

Human peritoneal macrophages were stimulated in vitro with beta-1,3-D-polyglucose-derivatized microbeads (GDM) or soluble aminated beta-1,3-D-polyglucose (AG) in combination with lipoproteins. The release of interleukin 1 (IL-1) was analysed in cell supernatants in a thymocyte proliferation assay. We report that the release of IL-1 is markedly enhanced in macrophages stimulated with polyglucose in either form in combination with native low-density lipoprotein (LDL) or acetyl LDL at a concentration of 100 micrograms/ml. By increasing the amount of lipoproteins up to 10-fold, the IL-1 release decreased sharply. There was only a slight increase in activity when high-density lipoprotein (HDL) or very low-density lipoprotein (VLDL) were added. Other stimulatory agents, such as gamma interferon (IFN-gamma) and lipopolysaccharide (LPS) showed about half the activity of polyglucose. There was no significant difference between native LDL and acetyl LDL in potentiating effect. Our observations also suggest that the potentiating effect of LDL or acetyl LDL is not dependent on binding to their specific receptors. These findings provide a connection between macrophages, lipoproteins, and cytokines with regard to their role in the inflammatory response.

Release of TNF‐α From In Vitro‐Stimulated Monocytes is Negatively Associated with Serum Levels of Apolipoprotein B in Patients with Type 2 Diabetes

“…Furthermore, the production of TNF‐α in the subgroup of diabetic patients treated with the cholesterol‐lowering drug simvastatin did not differ from that of the healthy control subjects. This is consistent with earlier in vitro studies, which showed that addition of serum lipids to macrophage cultures inhibited cytokine release [28, 29]. At the same time, a pleiotropic effect of simvastatin cannot be excluded, because the addition of the drug directly to cultures of human monocytes dramatically augments LPS‐stimulated production of TNF‐α and other cytokines in these cells [30].…”

Evidence that Tumour Necrosis Induced by Aminated β1‐3D Polyglucose is Mediated by a Concerted Action of Local and Systemic Cytokines

“…The unusually strong and rapid IL-I release brought about by AG (significanily stronger than by LPS [17]) suggests a role for IL-I in AGmediated lutnour necrosis. Nakamura ct al.…”

CD36 coordinates NLRP3 inflammasome activation by facilitating intracellular nucleation of soluble ligands into particulate ligands in sterile inflammation

“…Although oxLDL has been known to trigger IL-1β production in foam cells 48, 49, 50 , many of these studies were carried out before identification of the NLRP3-inflammasome. Our work provides the molecular mechanism for how oxLDL induces macrophage secretion of IL-1β by showing that CD36 binding of this ligand controls its engagement of the two necessary pathways for full inflammasome activation: Signal 1 via the TLRs and Signal 2 via the NLRs.…”