keyword
https://read.qxmd.com/read/26159927/intranuclear-interactomic-inhibition-of-nf-%C3%AE%C2%BAb-suppresses-lps-induced-severe-sepsis
#21
JOURNAL ARTICLE
Sung-Dong Park, So Yeong Cheon, Tae-Yoon Park, Bo-Young Shin, Hyunju Oh, Sankar Ghosh, Bon-Nyeo Koo, Sang-Kyou Lee
Suppression of nuclear factor-κB (NF-κB) activation, which is best known as a major regulator of innate and adaptive immune responses, is a potent strategy for the treatment of endotoxic sepsis. To inhibit NF-κB functions, we designed the intra-nuclear transducible form of transcription modulation domain (TMD) of RelA (p65), called nt-p65-TMD, which can be delivered effectively into the nucleus without influencing the cell viability, and work as interactomic inhibitors via disruption of the endogenous p65-mediated transcription complex...
August 28, 2015: Biochemical and Biophysical Research Communications
https://read.qxmd.com/read/25889879/attenuation-of-microglial-activation-in-a-mouse-model-of-alzheimer-s-disease-via-nfat-inhibition
#22
JOURNAL ARTICLE
Lalida Rojanathammanee, Angela M Floden, Gunjan D Manocha, Colin K Combs
BACKGROUND: Amyloid β (Aβ) peptide is hypothesized to stimulate microglia to acquire their characteristic proinflammatory phenotype in Alzheimer's disease (AD) brains. The specific mechanisms by which Aβ leads to microglial activation remain an area of interest for identifying attractive molecular targets for intervention. Based upon the fact that microglia express the proinflammatory transcription factor, nuclear factor of activated T cells (NFAT), we hypothesized that NFAT activity is required for the Aβ-stimulated microgliosis that occurs during disease...
2015: Journal of Neuroinflammation
https://read.qxmd.com/read/25779441/attenuation-of-microglial-activation-in-a-mouse-model-of-alzheimer-s-disease-via-nfat-inhibition
#23
JOURNAL ARTICLE
Lalida Rojanathammanee, Angela M Floden, Gunjan D Manocha, Colin K Combs
BACKGROUND: Amyloid β (Aβ) peptide is hypothesized to stimulate microglia to acquire their characteristic proinflammatory phenotype in Alzheimer's disease (AD) brains. The specific mechanisms by which Aβ leads to microglial activation remain an area of interest for identifying attractive molecular targets for intervention. Based upon the fact that microglia express the proinflammatory transcription factor, nuclear factor of activated T cells (NFAT), we hypothesized that NFAT activity is required for the Aβ-stimulated microgliosis that occurs during disease...
December 2015: Journal of Neuroinflammation
https://read.qxmd.com/read/23624600/a-combination-of-fluorescent-nfat-and-h2b-sensors-uncovers-dynamics-of-t-cell-activation-in-real-time-during-cns-autoimmunity
#24
JOURNAL ARTICLE
Dmitri Lodygin, Francesca Odoardi, Christian Schläger, Henrike Körner, Alexandra Kitz, Michail Nosov, Jens van den Brandt, Holger M Reichardt, Michael Haberl, Alexander Flügel
Multiple sclerosis is an autoimmune disease of the central nervous system (CNS) that is initiated when self-reactive T cells enter the brain and become locally activated after encountering their specific nervous antigens. When and where the disease-relevant antigen encounters occur is unclear. Here we combined fluorescently labeled nuclear factor of activated T cells (NFAT) with histone protein H2B to create a broadly applicable molecular sensor for intravital imaging of T cell activation. In experimental autoimmune encephalomyelitis, an animal model for multiple sclerosis, we report that effector T cells entering the CNS become activated after short contacts with leptomeningeal phagocytes...
June 2013: Nature Medicine
https://read.qxmd.com/read/23468550/pomegranate-polyphenols-and-extract-inhibit-nuclear-factor-of-activated-t-cell-activity-and-microglial-activation-in-vitro-and-in-a-transgenic-mouse-model-of-alzheimer-disease
#25
JOURNAL ARTICLE
Lalida Rojanathammanee, Kendra L Puig, Colin K Combs
Alzheimer disease (AD) brain is characterized by extracellular plaques of amyloid β (Aβ) peptide with reactive microglia. This study aimed to determine whether a dietary intervention could attenuate microgliosis. Memory was assessed in 12-mo-old male amyloid precursor protein/presenilin 1 (APP/PS1) transgenic mice via Barnes maze testing followed by division into either a control-fed group provided free access to normal chow and water or a treatment group provided free access to normal chow and drinking water supplemented with pomegranate extract (6...
May 2013: Journal of Nutrition
https://read.qxmd.com/read/22528479/differential-expression-and-hiv-1-regulation-of-%C3%AE-opioid-receptor-splice-variants-across-human-central-nervous-system-cell-types
#26
JOURNAL ARTICLE
Seth M Dever, Ruqiang Xu, Sylvia Fitting, Pamela E Knapp, Kurt F Hauser
The μ-opioid receptor (MOR) is known to undergo extensive alternative splicing as numerous splice variants of MOR have been identified. However, the functional significance of MOR variants, as well as how splice variants other than MOR-1 might differentially regulate human immunodeficiency virus type-1 (HIV-1) pathogenesis in the central nervous system (CNS), or elsewhere, has largely been ignored. Our findings suggest that there are specific differences in the MOR variant expression profile among CNS cell types, and that the expression levels of these variants are differentially regulated by HIV-1...
June 2012: Journal of Neurovirology
https://read.qxmd.com/read/21435337/cyclophilin-c-associated-protein-regulation-of-phagocytic-functions-via-nfat-activation-in-macrophages
#27
JOURNAL ARTICLE
Rei Yamaguchi, Masahiro Hosaka, Seiji Torii, Ni Hou, Nobuhito Saito, Yuhei Yoshimoto, Hideaki Imai, Toshiyuki Takeuchi
Experimental cerebral ischemia has been reportedly alleviated by the immunosuppressive agent cyclosporin A (CsA). Cyclophilin C-associated protein (CyCAP) was proposed to be an endogenous equivalent of CsA; CsA- and CyCAP-targeting protein cyclophilin C have attracted extensive attention regarding their ischemia-alleviating mechanisms. In this study we have introduced the specific CyCAP antibody for evaluating its distribution in the rat ischemic brain after middle cerebral artery occlusion. During the recovery of cerebral ischemia in rats, CyCAP was highly expressed in the activated microglia/macrophages in the ischemic lesion...
June 23, 2011: Brain Research
https://read.qxmd.com/read/21317391/uridine-5-diphosphate-induces-chemokine-expression-in-microglia-and-astrocytes-through-activation-of-the-p2y6-receptor
#28
JOURNAL ARTICLE
Beomsue Kim, Hey-kyeong Jeong, Jong-hyeon Kim, Sang Yoon Lee, Ilo Jou, Eun-hye Joe
Chemokines play critical roles in inflammation by recruiting inflammatory cells to injury sites. In this study, we found that UDP induced expression of chemokines CCL2 (MCP-1) and CCL3 (MIP-1α) in microglia, astrocytes, and slice cultures by activation of P2Y(6). Interestingly, CCL2 was more highly expressed than CCL3. However, CCL2 synthesis kinetics in response to UDP differed in microglia and astrocytes; microglia rapidly produced small amounts of CCL2, whereas astrocytes continuously synthesized large amounts of CCL2, resulting in a high ultimate level of the chemokine...
March 15, 2011: Journal of Immunology
https://read.qxmd.com/read/20967884/response-of-transcription-factor-nfatc3-to-excitotoxic-and-traumatic-brain-insults-identification-of-a-subpopulation-of-reactive-astrocytes
#29
JOURNAL ARTICLE
María C Serrano-Pérez, Eduardo D Martín, Cecilia F Vaquero, Iñigo Azcoitia, Soledad Calvo, Eva Cano, Pedro Tranque
Astrocytes react to brain injury triggering neuroinflammatory processes that determine the degree of neuronal damage. However, the signaling events associated to astrocyte activation remain largely undefined. The nuclear factor of activated T-cells (NFAT) is a transcription factor family implicated in activation of immune cells. We previously characterized the expression of NFAT isoforms in cultured astrocytes, and NFAT activation in response to mechanical lesion. Here we analyze NFATc3 in two mouse models of inflammatory brain damage: hippocampal excitotoxicity induced by intracerebral kainic acid (KA) injection and cortical mechanical lesion...
January 2011: Glia
https://read.qxmd.com/read/20631193/microglial-phenotype-is-regulated-by-activity-of-the-transcription-factor-nfat-nuclear-factor-of-activated-t-cells
#30
JOURNAL ARTICLE
Kumi Nagamoto-Combs, Colin K Combs
The transcription factor family, nuclear factor of activated T cells (NFAT), regulates immune cell phenotype. Four different calcium/calmodulin-regulated isoforms have been identified in the periphery, but isoform expression in microglia, the resident immune cells of the CNS, has not been fully defined. In this study microglial NFAT isoform expression and involvement in regulating inflammatory responses in murine primary microglia culture was examined. Western blot analysis demonstrated robust detection of NFATc1 and c2 isoforms in microglia...
July 14, 2010: Journal of Neuroscience
https://read.qxmd.com/read/20477948/p2x7-receptor-activation-induces-cxcl2-production-in-microglia-through-nfat-and-pkc-mapk-pathways
#31
JOURNAL ARTICLE
Miho Shiratori, Hidetoshi Tozaki-Saitoh, Mai Yoshitake, Makoto Tsuda, Kazuhide Inoue
Microglia plays an important role in many neurodegenerative conditions. ATP leaked or released by damaged cells triggers microglial activation through P2 receptors, and stimulates the release of oxygen radicals, proinflammatory cytokines and chemokines from activated microglia. However, little is known about mechanisms underlying ATP-induced chemokine release from microglia. In this study, we found that a high concentration of ATP induces the mRNA expression and release of CXCL2 from microglia. A similar effect was observed following treatment of microglia with a P2X7 receptor (P2X7R) agonist, 2'-and 3'-O-(4-benzoylbenzoyl) ATP, and this was inhibited by pre-treatment with a P2X7R antagonist, Brilliant Blue G...
August 2010: Journal of Neurochemistry
https://read.qxmd.com/read/19014371/activation-of-p2x7-receptors-induces-ccl3-production-in-microglial-cells-through-transcription-factor-nfat
#32
JOURNAL ARTICLE
Ayako Kataoka, Hidetoshi Tozaki-Saitoh, Yui Koga, Makoto Tsuda, Kazuhide Inoue
Microglia are implicated as a source of diverse proinflammatory factors in the CNS. Extracellular nucleotides are well known to be potent activators of glial cells and trigger the release of cytokines from microglia through purinergic receptors. However, little is known about the role of purinoceptors in microglial chemokine release. In this study, we found that high concentrations of ATP evoked release of CC-chemokine ligand 3 (CCL3)/macrophage inflammatory protein-1alpha from MG-5 cells, a mouse microglial cell line, and rapid up-regulation of CCL3 mRNA was elicited within 30 min of ATP stimulation...
January 2009: Journal of Neurochemistry
https://read.qxmd.com/read/18293408/calcium-calcineurin-signaling-in-primary-cortical-astrocyte-cultures-rcan1-4-and-cyclooxygenase-2-as-nfat-target-genes
#33
JOURNAL ARTICLE
Andrea Canellada, Belén G Ramirez, Takashi Minami, Juan Miguel Redondo, Eva Cano
The calcineurin/nuclear factor of activated T cells (NFAT) signaling pathway mediates important cell responses to calcium, but its activity and function in astrocytes have remained unclear. We show that primary cortical astrocyte cultures express the regulatory and catalytic subunits of the phosphatase calcineurin as well as the calcium-regulated NFAT family members (NFATc1, c2, c3, and c4). NFATs are activated by calcium-mobilizing agents in astrocytes, and this activation is blocked by the calcineurin inhibitor cyclosporine A...
May 2008: Glia
https://read.qxmd.com/read/10876802/-neurotransmitter-atp-and-cytokine-release
#34
REVIEW
K Morigiwa, Y Fukuda, M Yamashita
Microglia, the resident macrophages in the central nervous system (CNS), are rapidly activated upon trauma or ischemic injury, releasing cytokines and undertaking tissue repair. Recent studies have indicated that CNS immune cells express ionotropic P2X and metabotropic P2Y purinoceptors and undergo functional changes in response to extracellular ATP. Non-stimulated cultured rat retinal microglia expressed metabotropic P2U(P2Y2, P2Y4) and ionotropic P2Z(P2X7) purinoceptors equally, whereas in LPS-stimulated microglia, P2Z and its CA2+ response became dominant...
April 2000: Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica
https://read.qxmd.com/read/10224077/p2x7-p2z-purinoreceptor-mediated-activation-of-transcription-factor-nfat-in-microglial-cells
#35
JOURNAL ARTICLE
D Ferrari, C Stroh, K Schulze-Osthoff
ATP is released from neurons and other cell types during several physiological and stress conditions under which it exerts various biological effects upon binding to purinoreceptors. A rather peculiar purinoreceptor called P2X7/P2Z is expressed on microglial and other myeloic cells. Although increasing evidence implicates an important role for P2Z in inflammatory processes, little information exists about underlying signaling pathways. Here, we report that in N9 microglial cells, extracellular ATP potently activates nuclear factor of activated T cells (NFAT), a central transcription factor involved in cytokine gene expression...
May 7, 1999: Journal of Biological Chemistry
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