Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Hung HC

PROVIDER: S-EPMC9017628 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Publications

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

Hung Hao-Chang HC Tsai Sheng-Feng SF Sie Shih-Ren SR Kuo Yu-Min YM

Immunity, inflammation and disease 20220501 5

<h4>Introduction</h4>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.<h4>Methods</h4>This study aimed to investigate the effects of high glucose on low-dose lipopolysaccharide (LPS)-induced activations of inflammation-related ...[more]

PMID: 35478445

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Project description:Microglia are the primary immunocompetent cells in brain tissue and microglia-mediated inflammation is associated with the pathogenesis of various neuronal disorders. Recently, many studies have shown that mesenchymal stem cells (MSCs) display a remarkable ability to modulate inflammatory and immune responses through the release of a variety of bioactive molecules, thereby protecting the central nervous system. Previously, we reported that MSCs have the ability to modulate inflammatory responses in a traumatic brain injury model and that the potential mechanisms may be partially attributed to upregulated TNF-? stimulated gene/protein 6 (TSG-6) expression. However, whether TSG-6 exerts an anti-inflammatory effect by affecting microglia is not fully understood. In this study, we investigated the anti-inflammatory effects of MSCs and TSG-6 in an in vitro lipopolysaccharide (LPS)-induced BV2 microglial activation model. We found that MSCs and TSG-6 significantly inhibited the expression of pro-inflammatory mediators in activated microglia. However, MSC effects on microglia were attenuated when TSG-6 expression was silenced. In addition, we found that the activation of nuclear factor (NF)-?B and mitogen-activated protein kinase (MAPK) pathways in LPS-stimulated BV2 microglial cells was significantly inhibited by TSG-6. Furthermore, we found that the presence of CD44 in BV2 microglial cells was essential for MSC- and TSG-6-mediated inhibition of pro-inflammatory gene expression and of NF-?B and MAPK activation in BV2 microglial cells. The results of this study suggest that MSCs can modulate microglia activation through TSG-6 and that TSG-6 attenuates the inflammatory cascade in activated microglia. Our study indicates that novel mechanisms are responsible for the immunomodulatory effect of MSCs on microglia and that MSCs, as well as TSG-6, might be promising therapeutic agents for the treatment of neurotraumatic injuries or neuroinflammatory diseases associated with microglial activation.

Project description:Glutamine (Gln) is a nonessential ?-amino acid for protein biosynthesis. However, the mechanism through which Gln regulates NO production in microglial cells is still unclear. In this study, we investigated whether the presence or absence of Gln affects NO production in lipopolysaccharide (LPS)-stimulated BV2 microglial cells. Our data revealed that Gln depletion decreased cell viability accompanied by mild cytotoxicity, and blocked LPS-induced NO production concomitant with a significant decrease in inducible NO synthase (iNOS) expression. Additionally, Gln depletion for 24 h blocked the restoration of LPS-mediated NO production in the presence of Gln, suggesting that Gln depletion caused long-term immune deprivation. In particular, sodium-coupled amino acid transporter 1 and 2 (SNAT1 and SNAT2), which are the main Gln transporters, were highly upregulated in LPS-stimulated BV2 microglial cells, in the presence of Gln accompanied by NO production. Regardless of the presence of Gln, LPS positively stimulated nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression, and transient Nrf2 knockdown and HO-1 inhibition stimulated LPS-induced NO production and iNOS expression; however, transient Nrf2 knockdown did not affect SNAT1 and SNAT2 expression, indicating that Gln transporters, SNAT1 and SNAT2, were not regulated by Nrf2, which downregulated the HO-1-mediated NO production. Moreover, Gln depletion significantly reduced LPS-induced extracellular signal-regulated kinase (ERK) phosphorylation; furthermore, a specific ERK inhibitor, PD98059, and transient ERK knockdown attenuated LPS-stimulated NO production and iNOS expression, in the presence of Gln, accompanied by downregulation of SNAT1 and SNAT2, suggesting that the ERK signaling pathway was related to LPS-mediated NO production via SNAT1 and SNAT2. Altogether, our data indicated that extracellular Gln is vital for NO production from microglia in inflammatory conditions.

Dataset Information

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

Introduction

Methods

Results

Conclusion

Publications

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

Similar Datasets

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