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.
Keywords: NF-κB; TLR4; diabetes; neuroinflammation; p38.
© 2022 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.