• Title/Summary/Keyword: activated microglia

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Signaling Pathways Controlling Microglia Chemotaxis

  • Fan, Yang;Xie, Lirui;Chung, Chang Y.
    • Molecules and Cells
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    • v.40 no.3
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    • pp.163-168
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    • 2017
  • Microglia are the primary resident immune cells of the central nervous system (CNS). They are the first line of defense of the brain's innate immune response against infection, injury, and diseases. Microglia respond to extracellular signals and engulf unwanted neuronal debris by phagocytosis, thereby maintaining normal cellular homeostasis in the CNS. Pathological stimuli such as neuronal injury induce transformation and activation of resting microglia with ramified morphology into a motile amoeboid form and activated microglia chemotax toward lesion site. This review outlines the current research on microglial activation and chemotaxis.

Potential Role of Ursodeoxycholic Acid in Suppression of Nuclear Factor Kappa B in Microglial Cell Line (BV-2)

  • Joo, Seong-Soo;Won, Tae-Joan;Lee, Do-Ik
    • Archives of Pharmacal Research
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    • v.27 no.9
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    • pp.954-960
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    • 2004
  • Expression of the NF-$textsc{k}$B-dependent genes responsible for inflammation, such as TNF-$\alpha$, IL-1$\beta$, and nitric oxide synthase (NOS), contributes to chronic inflammation which is a major cause of neurodegenerative diseases (i.e. Alzheimer's disease). Although NF-$textsc{k}$B plays a biphasic role in different cells like neurons and microglia, controlling the activation of NF-$textsc{k}$B is important for its negative feedback in either activation or inactivation. In this study, we found that ursodeoxycholic acid (UDCA) inhibited I$textsc{k}$B$\alpha$ degradation to block expression of the NF-$textsc{k}$B-dependent genes in microglia when activated by $\beta$-amyloid peptide (A$\beta$). We also showed that when microglia is activated by $A\beta$42, the expression of A20 is suppressed. These findings place A20 in the category of ' protective ' genes, protecting cells from pro-inflammatory reper-toires induced in response to inflammatory stimuli in activated microglia via NF-$textsc{k}$B activation. In light of the gene and proteins for NF-$textsc{k}$B-dependent gene and inactivator for NF-$textsc{k}$B (I$textsc{k}$B$\alpha$), the observations now reported suggest that UDCA plays a role in supporting the attenuation of the production of pro-inflammatory cytokines and NO via inactivation of NF-$textsc{k}$B. Moreover, an NF-$textsc{k}$B inhibitor such as A20 can collaborate and at least enhance the anti-inflammatory effect in microglia, thus giving a potent benefit for the treatment of neurodegenerative diseases such as AD.uch as AD.

Regulation of $Ca^{2+}$ Influx by Membrane Potential in Microglia

  • Lee, Jungsun;Uhm, Dae-Yong;Sungkwon Chung
    • Proceedings of the Korean Biophysical Society Conference
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    • 2002.06b
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    • pp.39-39
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    • 2002
  • Microglia are known to have an important function as brain macrophage during immunological processes, oncogenesis, and regeneration in the central nervous system (CNS). A wide variety of ion channels have been identified and characterized in microglia including inward rectifier $K^{+}$ channel (Kir), voltage dependent $K^{+}$ channel (Kv), $Ca^{2+}$-release activated $Ca^{2+}$ channel (CRAC).(omitted)

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Flavonoids as anti-inflammatory and neuroprotective agents

  • Lee, Heesu;Selvaraj, Baskar;Yoo, Ki Yeon;Ko, Seong-Hee
    • International Journal of Oral Biology
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    • v.45 no.2
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    • pp.33-41
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    • 2020
  • Neuroinflammation is known as the main mechanism implicated in the advancement of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. The main feature of neuroinflammation is associated with the activation of microglia. The activated microglia increase proinflammatory cytokine production and induce progressive neuronal cell death. Citrus flavonoids show neuroprotective effects that are associated with the anti-inflammatory action of flavonoids in neurodegenerative diseases. Among these citrus flavonoids, kaempferol, naringin, and nobiletin show inhibitory effects on nuclear factor-κB and mitogen-activated protein kinase signaling pathways that can modulate inflammatory conditions in microglial cells. In the present review, we present the anti-inflammatory activities of citrus flavonoids and therapeutic potential of flavonoids as neuroprotective agents.

Inhibitory Action of Minocycline on Lipopolysaccharide-Induced Release of Nitric Oxide and Prostaglandin E2 in BV2 Microglial Cells

  • Kim, Sung-Soo;Kong, Pil-Jae;Kim, Bong-Seong;Sheen, Dong-Hyuk;Nam, Su-Youn;Chun, Wan-Joo
    • Archives of Pharmacal Research
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    • v.27 no.3
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    • pp.314-318
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    • 2004
  • Microglia are the major inflammatory cells in the central nervous system and become activated in response to brain injuries such as ischemia, trauma, and neurodegenerative diseases including Alzheimer's disease (AD). Moreover, activated microglia are known to release a variety of proinflammatory cytokines and oxidants such as nitric oxide (NO). Minocycline is a semi-synthetic second-generation tetracycline that exerts anti-inflammatory effects that are completely distinct form its antimicrobial action. In this study, the inhibitory effects of minocycline on NO and prostaglandin E$_2$ (PGE$_2$) release was examined in lipopolysaccharides (LPS)-challenged BV2 murine microglial cells. Further, effects of minocycline on inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression levels were also determined. The results showed that minocycline significantly inhibited NO and PGE$_2$ production and iNOS and COX-2 expression in BV2 microglial cells. These findings suggest that minocycline should be evaluated as potential therapeutic agent for various pathological conditions due to the excessive activation of microglia.

Immunohistochemical localization of galectin-3 in the brain with Theiler's murine encephalomyelitis virus (DA strain) infection

  • Shin, Taekyun;Carrillo-Salinas, Francisco J.;Martinez, Ana Feliu;Mecha, Miriam;Guaza, Carmen
    • Korean Journal of Veterinary Research
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    • v.53 no.3
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    • pp.159-162
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    • 2013
  • Galectin-3 is a ${\beta}$-galactoside-binding lectin that plays a role in neuroinflammation through cell migration, proliferation, and apoptosis. In the present study, regulation of galectin-3 was examined in the brain of mice infected with the Daniel strain of Theiler's murine encephalomyelitis virus (TMEV) at days 7 and 81 post-infection by immunohistochemistry. Immunohistochemistry revealed that galectin-3 was mainly localized in ionized calcium-binding adapter 1-positive macrophages/activated microglia, but not in Iba-1-positive ramified microglia. Galectin-3 was also weakly detected in some astrocytes in the same encephalitic lesions, but not in neurons and oligodendrocytes. Collectively, the present findings suggest that galectin-3, mainly produced by activated microglia/macrophages, may be involved in the pathogenesis of virus induced acute inflammation in the early stage as well as the chronic demyelinating lesions in Daniel strain of TMEV induced demyelination model.

Effects of Curcumin on the Microglial Activation (Curcumin이 microglia의 활성화에 미치는 영향)

  • 정기경;이상진;이선우;강석연;김태균;강주혜;홍성렬;주일로;김승희
    • YAKHAK HOEJI
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    • v.44 no.5
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    • pp.448-454
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    • 2000
  • Microglia, brain resident macrophages, play a central role in the inflammatory responses of the brain and are activated in brain injuries and several neurodegenerative diseases such as Alzheimer's and Parkinson's disease, thereby aggravating the course of these diseases. In this study, the effects of plantderived compounds such as curcumin or gingerol on the microglial activation were examined. Microglial cultures were prepared from 2~3 week mixed primary glial cultures obtained from the cerebral cortex of 1~2 day old rats and identified by immunocytochemistry using microglial-specific antibody OX-42. Microglia were activated by lipopolysaccharide (LPS) and interferon-${\gamma}$ (IFN-${\gamma}$) and the effect of curcumin or 6-gingerol on the microglial activation was examined. Specific parameters measured to monitor microglial activation were nitric oxide (NO), prostaglandin E$_2$(PGE$_2$) and tumor necrosis factor-$\alpha$ (TNF-$\alpha$) release. Curcumin (1~10 $\mu$M) inhibited NO release induced by LPS and IFN-${\gamma}$ in a dose-dependent manner whereas 6-gingerol (2~20 $\mu$M) did not have any effect on LPS/IFN-${\gamma}$-induced NO release. The levels of PGE$_2$and TNF-$\alpha$ induced by LPS and IFN-${\gamma}$ were also inhibited by 1~10 $\mu$M curcumin in a dose-dependent manner. These results showed that curcumin could modulate microglial activation.

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Betulinic Acid Inhibits LPS-Induced MMP-9 Expression by Suppressing NF-kB Activation in BV2 Microglial Cells

  • Lee, Jae-Won;Choi, Yong-Joon;Kim, Song-In;Lee, Sue-Young;Kang, Sang-Soo;Kim, Nam-Ho;Kwon, Yong-Soo;Lee, Hee-Jae;Chun, Wan-Joo;Kim, Sung-Soo
    • Biomolecules & Therapeutics
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    • v.19 no.4
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    • pp.431-437
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    • 2011
  • Aberrant activation of microglia has been reported to cause neuronal damages by releasing a variety of pro-inflammatory cytokines. Besides where microglia become active, damages have been also observed in remote places, which is considered due to the migration of activated microglia. Therefore, an agent that could suppress abnormal activation of microglia and their subsequent migration might be valuable in activated microglia-related brain pathologies. The objective of the present study was to evaluate anti-inflammatory effects of betulinic acid on lipopolysaccharide (LPS)-stimulated BV2 microglial cells. Pretreatment of betulinic acid significantly attenuated LPS-induced NO production and protein expression of iNOS. Betulinic acid also significantly suppressed LPS-induced release and expression of cytokines such as TNF-${\alpha}$ and IL-$1{\beta}$. Furthermore, betulinic acid significantly uppressed LPS-induced MMP-9 expression, which has been suggested to play an important role in the migration of activated microglia. In order to understand the possible mechanism by which betulinic acid suppresses LPS-induced cytokine production and migration of microglia, the role of NF-kB, a major pro-inflammatory transcription factor, was examined. Betulinic acid significantly suppressed LPS-induced degradation of IKB, which retains NF-kB in the cytoplasm. Therefore, nuclear translocation of NF-kB upon LPS stimulation was significantly suppressed with betulinic acid. Taken together, the present study for the first time demonstrates that betulinic acid possesses anti-inflammatory activity through the suppression of nuclear translocation of NF-kB in BV2 microglial cells.

Inhibitory Activity of Nitric Oxide Synthase and Peroxynitrite Scavenging Activity of Extracts of Perilla frutescens (들깨 잎 추출물의 Nitric Oxide Synthase 저해활성 및 Peroxynitrite 소거활성)

  • Kim, Jae-Yeon;Kim, Ji-Sun;Jung, Chan-Sik;Jin, Chang-Bae;Ryu, Jae-Ha
    • Korean Journal of Pharmacognosy
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    • v.38 no.2 s.149
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    • pp.170-175
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    • 2007
  • Activated microglia by neuronal injury or inflammatory stimulation overproduce nitric oxide (NO) by inducible nitric oxide synthase (iNOS) and reactive oxygen species (ROS) such as superoxide anion, resulting in neurodegenerative diseases. The toxic peroxynitrite (ONOO$^-$), the reaction product of NO and superoxide anion further contributes to oxidative neurotoxicity. We tried to evaluate the effects of two kinds of varieties of Perilla frutescens var japnica Hara on the NO production in lipopolysaccharide (LPS)-activated microglia. The perilla cultivars of Namcheondeulkkae (NC) and Boradeulkkae (BR) were developed by pure line from the local variety and by a cross between 'deulkkae' and 'chajogi', respectively. Spirit, hexane, chloroform and butanol fractions of the leaves of NC and BR inhibited the production of NO in LPS-activated microglia. The fractions of BR showed stronger activity than NC and the spirit extracts was the most potent in both cultivars. The solvent fractions of BR suppressed the expression of protein and mRNA of iNOS in LPS-activated microglial cells. Moreover, the extracts of NC and BR showed the activity of peroxynitrite scavenging in cell free bioassay system. These results imply that Namcheondeulkkae and Boradeulkkae might have neuroprotective activity through the inhibition of NO production by activated microglial cells and peroxynitrite scavenging activity.

Distinct Features of Brain-Resident Macrophages: Microglia and Non-Parenchymal Brain Macrophages

  • Lee, Eunju;Eo, Jun-Cheol;Lee, Changjun;Yu, Je-Wook
    • Molecules and Cells
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    • v.44 no.5
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    • pp.281-291
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    • 2021
  • Tissue-resident macrophages play an important role in maintaining tissue homeostasis and innate immune defense against invading microbial pathogens. Brain-resident macrophages can be classified into microglia in the brain parenchyma and non-parenchymal brain macrophages, also known as central nervous system-associated or border-associated macrophages, in the brain-circulation interface. Microglia and non-parenchymal brain macrophages, including meningeal, perivascular, and choroid plexus macrophages, are mostly produced during embryonic development, and maintained their population by self-renewal. Microglia have gained much attention for their dual roles in the maintenance of brain homeostasis and the induction of neuroinflammation. In particular, diverse phenotypes of microglia have been increasingly identified under pathological conditions. Single-cell phenotypic analysis revealed that microglia are highly heterogenous and plastic, thus it is difficult to define the status of microglia as M1/M2 or resting/activated state due to complex nature of microglia. Meanwhile, physiological function of non-parenchymal brain macrophages remain to be fully demonstrated. In this review, we have summarized the origin and signatures of brain-resident macrophages and discussed the unique features of microglia, particularly, their phenotypic polarization, diversity of subtypes, and inflammasome responses related to neurodegenerative diseases.