Abstract

Persistent inflammatory reactions in microglial cells are strongly associated with neurodegenerative pathogenesis. Additionally, geranylgeraniol (GGOH), a plant-derived isoprenoid, has been found to improve inflammatory conditions in several animal models. It has also been observed that its chemical structure is similar to that of the side chain of menaquinone-4, which is a vitamin K2 sub-type that suppresses inflammation in mouse-derived microglial cells. In this study, we investigated whether GGOH has a similar anti-inflammatory effect in activated microglial cells. Particularly, mouse-derived MG6 cells pre-treated with GGOH were exposed to lipopolysaccharide (LPS). Thereafter, the mRNA levels of pro-inflammatory cytokines were determined via qRT-PCR, while protein expression levels, especially the expression of NF-κB signaling cascade-related proteins, were determined via Western blot analysis. The distribution of NF-κB p65 protein was also analyzed via fluorescence microscopy. Thus, it was observed that GGOH dose-dependently suppressed the LPS-induced increase in the mRNA levels of Il-1β, Tnf-α, Il-6, and Cox-2. Furthermore, GGOH inhibited the phosphorylation of TAK1, IKKα/β, and NF-κB p65 proteins as well as NF-κB nuclear translocation induced by LPS while maintaining IκBα expression. We showed that GGOH, similar to menaquinone-4, could alleviate LPS-induced microglial inflammation by targeting the NF-kB signaling pathway.

Highlights

  • GGOH inhibited the phosphorylation of TAK1, IKKα/β, and nuclear factor-κB (NF-κB) p65 proteins as well as NF-κB nuclear translocation induced by LPS while maintaining IκBα expression

  • We showed that GGOH, similar to menaquinone-4, could alleviate LPS-induced microglial inflammation by targeting the NF-kB signaling pathway

  • Microglia are brain-resident macrophage cells that act as the first immune defense in the brain and are responsible for maintaining central nervous system (CNS) homeostasis conditions [1,2]

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Summary

Introduction

Microglia are brain-resident macrophage cells that act as the first immune defense in the brain and are responsible for maintaining central nervous system (CNS) homeostasis conditions [1,2]. When the stimulus is temporal, cytokine production can be controlled to return to the normal physiological state [5] When such dangerous stimuli persist, the overproduction of inflammatory cytokines results in a cycle that further induces neuroinflammation [6,7]. This condition may cause neuronal cell loss, which can promote neurodegenerative pathogenesis. The aim of this study was to elucidate the anti-inflammatory effect of GGOHThaegraeifnosrteL, PthS-einadimuceodf itnhfilsamstumdaytiownaisntmo oeuluseci-ddaetreivtehdeManGt6i-miniflcaromgmliaaltoceryllse, fwfehcitchof isGaGcOonHfiargmaeindscteLllPlSin-iendthuactedis iunsfleadmams aatmionicrinogmliaoluasect-idveartiivoendmMoGd6elm[3i3cr,3o4g]l.iaBlyceclllasr,iwfyhinicgh thiseamcoolneficurmlaerdaccteilolnlinoef GthGatOiHs u, swede hasopaemtoicrloayglaialparecltiimvaitnioarnymfooudnedl a[3ti3o,3n4f]o. rByfucrltahreifryiinn-g vtehsetigmatoiloenc,uelsapr eacciatilolynroefgaGrdGiOngHt,hwe aeshsoocpiaetitoonlabyetwa epernelGimGiOnaHryanfodumndicartoigolniaflocrelflus.rther investigation, especially regarding the association between GGOH and microglial cells

Results
LPS-Induced Disappearance of IRAK1 in MG6 Cells and Its Reversal by GGOH
Materials
Cell Cultures and Treatment
Cell Viability Assay
RNA Extraction and Quantitative RT-PCR Assay
Immunoblot Analysis
Cytoplasmic-Nuclear Fractionation
Immunocytofluorescence
Statistical Analysis
Full Text
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