High glucose enhances lipopolysaccharide-induced inflammation in cultured BV2 microglial cell line.

INTRODUCTION: Diabetes mellitus emerges as a global health crisis and is related to the development of neurodegenerative diseases. Microglia, a population of macrophages-like cells, govern immune defense in the central nervous system. Activated microglia are known to play active roles in the pathogenesis of neurodegenerative diseases. METHODS: This study aimed to investigate the effects of high glucose on low-dose lipopolysaccharide (LPS)-induced activations of inflammation-related signaling molecules in cultured BV2 microglial cells. RESULTS: Compared to cells cultured in the normal glucose medium (NGM, 5.5 mM), the LPS-induced activation of NF-κB lasted longer in cells cultured in high glucose medium (HGM, 25 mM). HGM also enhanced the expression of inducible nitric oxide synthase (iNOS). Among the mitogen-activated protein kinases, HGM enhanced the LPS-induced phosphorylation of p38 without affecting the phosphorylation of Erk1/2 or JNK. BV2 cells cultured in HGM expressed higher levels of TLR4 than those cells cultured in NGM. CONCLUSION: High glucose aggravated LPS-induced inflammatory responses of microglia via enhancing the TLR4/p38 pathway and prolonging the activation of NF-κB/iNOS signaling. Controlling blood glucose levels is advised to manage neuroinflammation and related neurodegenerative diseases.

Lipofundin Mediates the Major Inhibition of Intravenous Propofol in IL-1ß Secretion and Phagocytosis of Staphylococcus aureus-Infected Macrophages.

Lipofundin is the solvent for propofol in the intravenous injection of Propofol-Lipuro® and is used in patients who need intravenous feeding to provide fatty acids and fat for energy. In addition to propofol, Lipofundin also affects the immune modulation of phagocytes. In a previous study, we reported that intravenous propofol effectively decreased Staphylococcus aureus-stimulated reactive oxygen species (ROS) levels, IL-1ß secretion, and phagocytosis in RAW264.7 macrophages. It is important to separately assess the effects of pure propofol, Lipofundin, and Propofol-Lipuro. By using an S. aureus-infected RAW264.7 macrophage model, the levels of secreted IL-1ß in cell supernatants were determined by ELISA. IL-1ß mRNA in cell pellets was further analyzed by quantitative polymerase chain reaction (qPCR), and Western blotting was performed to detect pro-IL-1ß synthesis. Total ROS levels were determined by a luminol chemiluminescence assay. Compared with pure propofol, treatment with clinically relevant concentrations of Propofol-Lipuro and Lipofundin obviously reduced IL-1ß secretion (>85% inhibition), S. aureus-stimulated ROS production (50% inhibition), and phagocytosis (>60% inhibition) to similar levels. Treatment with pure propofol alone significantly decreased IL-1ß mRNA levels and pro-IL-1ß protein synthesis, and slightly inhibited phagocytosis. In contrast, treatment with Propofol-Lipuro did not influence IL-1ß mRNA or pro-IL-1ß protein expression, even though treatment with Lipofundin increased the levels of both IL-1ß mRNA and its precursor protein. In conclusion, IL-1ß secretion is regulated at the posttranslational level. Lipofundin mediated the major effect of Propofol-Lipuro on the inhibition of IL-1ß secretion, ROS production, and phagocytosis in S. aureus-infected RAW264.7 cells.