TNF-alpha- and TRAIL-resistant glioma cells undergo autophagy-dependent cell death induced by activated microglia.


:The role of microglia, the brain resident macrophages, in glioma biology is still ill-defined. Despite their cytotoxic potential, these cells that significantly infiltrate the tumor mass seem to support tumor growth rather than tumor eradication. A proper activation of microglia anti-tumor activities within the tumor may provide a valuable additional arm of defense to immunotherapies against brain tumors. We herewith report a detailed characterization of (lipopolysaccharide and interferon-gamma)-induced anti-tumor activities of mouse primary microglia towards two TNF-alpha and TRAIL resistant glioma cell lines, in cell monolayer or spheroid cultures and in collagen-embedded tumor explants. Irrespective of the mouse strain, stimulated microglia secreted proteic factors that decreased proliferation and migration of these glioma cells and efficiently killed them. Death occurred specifically in glioma cells as demonstrated by the lack of toxicity of microglia supernatant towards primary cultures of astrocytes or neurons. Cell death was characterized by the early accumulation of acidic vesicles, phosphatidylserine exposure, appearance of double-membrane cytoplasmic vesicles, extensive zeiosis and a very late loss of DNA in cells that had lost membrane integrity. Inhibition of autophagosome formation efficiently protected glioma cells from death whereas caspase inhibition could only prevent DNA loss but not cytotoxicity. Death however, resulted from a blockade by microglia supernatant of the basal autophagic flux present in the glioma cells. These observations demonstrate that glioma cells resistant to apoptotic death ligands could be successfully and specifically killed through autophagy-dependent death induced by appropriately activated microglia.






Mora R,Abschuetz A,Kees T,Dokic I,Joschko N,Kleber S,Geibig R,Mosconi E,Zentgraf H,Martin-Villalba A,Régnier-Vigouroux A




Has Abstract


2009-04-01 00:00:00














  • Calcium waves between astrocytes from Cx43 knockout mice.

    abstract::Gap junctions are regarded as the primary pathway underlying propagation of Ca2+ waves between astrocytes, although signaling through extracellular space may also contribute. Results obtained from astrocytes cultured from sibling Cx43 knockout (KO) and wild-type (WT) mice in six litters showed that Ca2+ waves propagat...


    pub_type: 杂志文章


    authors: Scemes E,Dermietzel R,Spray DC

    更新日期:1998-09-01 00:00:00

  • Altered membrane physiology in Müller glial cells after transient ischemia of the rat retina.

    abstract::Inwardly rectifying K+ (Kir) channels have been implicated in the mediation of retinal K+ homeostasis by Muller glial cells. To assess possible involvement of altered glial K+ channel expression in ischemia-reperfusion injury, transient retinal ischemia was induced in rat eyes. Acutely isolated Muller cells from posti...


    pub_type: 杂志文章


    authors: Pannicke T,Uckermann O,Iandiev I,Biedermann B,Wiedemann P,Perlman I,Reichenbach A,Bringmann A

    更新日期:2005-04-01 00:00:00

  • ADAM-10 and ADAM-17 in the inflamed human CNS.

    abstract::Inflammatory demyelinating disorders of the CNS, such as multiple sclerosis (MS), are mediated, at least in part, by various cytokines and proteases. In the present study, we investigated the expression of A disintegrin and metalloproteinase (ADAM)-17, an important sheddase for various proteins, including tumor necros...


    pub_type: 杂志文章


    authors: Kieseier BC,Pischel H,Neuen-Jacob E,Tourtellotte WW,Hartung HP

    更新日期:2003-06-01 00:00:00

  • Cannabinoid CB2 receptor agonists protect the striatum against malonate toxicity: relevance for Huntington's disease.

    abstract::Cannabinoid agonists might serve as neuroprotective agents in neurodegenerative disorders. Here, we examined this hypothesis in a rat model of Huntington's disease (HD) generated by intrastriatal injection of the mitochondrial complex II inhibitor malonate. Our results showed that only compounds able to activate CB2 r...


    pub_type: 杂志文章


    authors: Sagredo O,González S,Aroyo I,Pazos MR,Benito C,Lastres-Becker I,Romero JP,Tolón RM,Mechoulam R,Brouillet E,Romero J,Fernández-Ruiz J

    更新日期:2009-08-15 00:00:00

  • Selective upregulation of inducible nitric oxide synthase (iNOS) by lipopolysaccharide (LPS) and cytokines in microglia: in vitro and in vivo studies.

    abstract::A role for free radicals has been proposed in infectious brain disease, where resident microglia cells upregulate the inducible nitric oxide synthase isoform (iNOS), and thus are capable of producing nitric oxide at enhanced rates. Using the constitutively expressed NADPH oxidase, microglial cells can generate superox...


    pub_type: 杂志文章


    authors: Possel H,Noack H,Putzke J,Wolf G,Sies H

    更新日期:2000-10-01 00:00:00

  • GLAST-CreERT2 mediated deletion of GDNF increases brain damage and exacerbates long-term stroke outcomes after focal ischemic stroke in mouse model.

    abstract::Focal ischemic stroke (FIS) is a leading cause of human death. Glial scar formation largely caused by reactive astrogliosis in peri-infarct region (PIR) is the hallmark of FIS. Glial cell-derived neurotrophic factor (GDNF) was originally isolated from a rat glioma cell-line supernatant and is a potent survival neurotr...


    pub_type: 杂志文章


    authors: Zhang N,Zhang Z,He R,Li H,Ding S

    更新日期:2020-11-01 00:00:00

  • IL-27 inhibits OSM-mediated TNF-alpha and iNOS gene expression in microglia.

    abstract::Elevated levels of Oncostatin M (OSM), an interleukin-6 family cytokine, have been observed in multiple sclerosis (MS), HIV-associated neurocognitive disorder (HAND), and glioblastoma (GBM); however, its effects within the CNS are not well understood. OSM regulates gene expression primarily by activating the JAK/STAT,...


    pub_type: 杂志文章


    authors: Baker BJ,Park KW,Qin H,Ma X,Benveniste EN

    更新日期:2010-07-01 00:00:00

  • Mice lacking NT-3, and its receptor TrkC, exhibit profound deficiencies in CNS glial cells.

    abstract::Neurotrophin-3 (NT-3) and its receptor TrkC are known to be important for neuronal survival. More recently, NT-3 has been implicated as playing a role in oligodendrocyte (OL) proliferation and survival in vitro. Examination of NT-3 and TrkC knockout mice revealed a reduction in NT-3-dependent neurons. To date, no stud...


    pub_type: 杂志文章


    authors: Kahn MA,Kumar S,Liebl D,Chang R,Parada LF,De Vellis J

    更新日期:1999-04-01 00:00:00

  • Motile membrane protrusions regulate cell-cell adhesion and migration of olfactory ensheathing glia.

    abstract::Olfactory ensheathing cells (OECs) are candidates for therapeutic approaches for neural regeneration due to their ability to assist axon regrowth in central nervous system lesion models. However, little is understood about the processes and mechanisms underlying migration of these cells. We report here that novel lame...


    pub_type: 杂志文章


    authors: Windus LC,Claxton C,Allen CL,Key B,St John JA

    更新日期:2007-12-01 00:00:00

  • A functional role of NMDA receptor in regulating the differentiation of oligodendrocyte precursor cells and remyelination.

    abstract::Differentiation of oligodendrocyte precursor cells (OPCs) is the most important event for the myelination of central nervous system (CNS) axons during development and remyelination in demyelinating diseases, while the underlying molecular mechanisms remain largely unknown. Here we show that NMDA receptor (NMDAR) is a ...


    pub_type: 杂志文章


    authors: Li C,Xiao L,Liu X,Yang W,Shen W,Hu C,Yang G,He C

    更新日期:2013-05-01 00:00:00

  • Ultrastructural relationships between noradrenergic nerve fibers and non-neuronal elements in the rat cerebral cortex.

    abstract::Pharmacological and biochemical data suggest that noradrenaline (NA)-containing fibers not only regulate the activity of cortical neurons but also influence the functional state of non-neuronal elements. In the present study, immunocytochemistry with an antiserum against NA, followed by silver-gold intensification of ...


    pub_type: 杂志文章


    authors: Paspalas CD,Papadopoulos GC

    更新日期:1996-06-01 00:00:00

  • Expression of glutamine synthetase and glutamate dehydrogenase in the latent phase and chronic phase in the kainate model of temporal lobe epilepsy.

    abstract::It has been suggested that astrocytic glutamate release or perturbed glutamate metabolism contributes to the proneness to epileptic seizures. Here we investigated whether astrocytic contents of the major glutamate degrading enzymes glutamine synthetase (GS) and glutamate dehydrogenase (GDH) decreases on moving from th...


    pub_type: 杂志文章


    authors: Hammer J,Alvestad S,Osen KK,Skare Ø,Sonnewald U,Ottersen OP

    更新日期:2008-06-01 00:00:00

  • Reactive astrocytes in myelin-deficient rat optic nerve reveal an altered distribution of orthogonal arrays of particles (OAP).

    abstract::Reactive astrocytes are a common feature of various pathological conditions within the CNS. Morphological changes of reactive astrocytes include an altered nucleus-cytoplasm relationship, nuclear indentations, an increased amount of intermediate filaments, and an immunologically immature phenotype. Additionally, the n...


    pub_type: 杂志文章


    authors: Rohlmann A,Gocht A,Wolburg H

    更新日期:1992-01-01 00:00:00

  • Characterization of microglia and macrophages in the central nervous system of rats: definition of the differential expression of molecules using standard and novel monoclonal antibodies in normal CNS and in four models of parenchymal reaction.

    abstract::This report describes the development of a new panel of monoclonal antibodies produced following immunization of mice with cultured rat microglial cells. Using these new reagents and previously defined antibodies that bind to microglia or macrophages, the responses of parenchymal microglia, perivascular "microglial" c...


    pub_type: 杂志文章


    authors: Flaris NA,Densmore TL,Molleston MC,Hickey WF

    更新日期:1993-01-01 00:00:00

  • Contrasting effects of mitogenic growth factors on myelination in neuron-oligodendrocyte co-cultures.

    abstract::Mitogenic growth factors play an important role in the initial stages of oligodendrocyte development, but their roles in the process of myelination itself remain less well defined. In order to study directly the effects of different growth factors on myelination, we used a purified in vitro co-culture system with dors...


    pub_type: 杂志文章


    authors: Wang Z,Colognato H,Ffrench-Constant C

    更新日期:2007-04-01 00:00:00

  • Molecular imaging of microglia/macrophages in the brain.

    abstract::Neuroinflammation perpetuates neuronal damage in many neurological disorders. Activation of resident microglia and infiltration of monocytes/macrophages contributes to neuronal injury and synaptic damage. Noninvasive imaging of these cells in vivo provides a means to monitor progression of disease as well as assess ef...


    pub_type: 杂志文章,评审


    authors: Venneti S,Lopresti BJ,Wiley CA

    更新日期:2013-01-01 00:00:00

  • Extensive and long-lasting changes of glial cells following transection of the postcommissural fornix in the adult rat.

    abstract::Injury to the adult brain results in the formation of a glial scar that involves both activated astroglia and microglia/macrophages. Although reactive gliosis has been linked to failure of axonal regeneration in the adult mammalian CNS, the spatio-temporal pattern of the postlesion responses in morphology and distribu...


    pub_type: 杂志文章


    authors: Stichel CC,Müller HW

    更新日期:1994-02-01 00:00:00

  • Mutation of ataxia-telangiectasia mutated is associated with dysfunctional glutathione homeostasis in cerebellar astroglia.

    abstract::Astroglial dysfunction plays an important role in neurodegenerative diseases otherwise attributed to neuronal loss of function. Here we focus on the role of astroglia in ataxia-telangiectasia (A-T), a disease caused by mutations in the ataxia-telangiectasia mutated (ATM) gene. A hallmark of A-T pathology is progressiv...


    pub_type: 杂志文章


    authors: Campbell A,Bushman J,Munger J,Noble M,Pröschel C,Mayer-Pröschel M

    更新日期:2016-02-01 00:00:00

  • WNT signaling represses astrogliogenesis via Ngn2-dependent direct suppression of astrocyte gene expression.

    abstract::Neural progenitor cells (NPCs) are sequentially specified into neurons and glia during the development of central nervous system. WNT/β-catenin signaling is known to regulate the balance between the proliferation and differentiation of NPCs during neurogenesis. However, the function of WNT/β-catenin signaling during g...


    pub_type: 杂志文章


    authors: Sun S,Zhu XJ,Huang H,Guo W,Tang T,Xie B,Xu X,Zhang Z,Shen Y,Dai ZM,Qiu M

    更新日期:2019-07-01 00:00:00

  • Intrinsic optical signals in the rat optic nerve: role for K(+) uptake via NKCC1 and swelling of astrocytes.

    abstract::Measurements of extracellular space volume and imaging of intrinsic optical signals (IOSs) have shown that neuronal activity increases light transmittance by causing cellular swelling. However, the cellular mechanisms underlying these volume changes and the contribution of astrocyte swelling to the changes in tissue v...


    pub_type: 杂志文章


    authors: MacVicar BA,Feighan D,Brown A,Ransom B

    更新日期:2002-02-01 00:00:00

  • RNA-sequencing reveals oligodendrocyte and neuronal transcripts in microglia relevant to central nervous system disease.

    abstract::Expression profiling of distinct central nervous system (CNS) cell populations has been employed to facilitate disease classification and to provide insights into the molecular basis of brain pathology. One important cell type implicated in a wide variety of CNS disease states is the resident brain macrophage (microgl...


    pub_type: 杂志文章


    authors: Solga AC,Pong WW,Walker J,Wylie T,Magrini V,Apicelli AJ,Griffith M,Griffith OL,Kohsaka S,Wu GF,Brody DL,Mardis ER,Gutmann DH

    更新日期:2015-04-01 00:00:00

  • Mitogen-activated protein kinase-signaling regulates the ability of Müller glia to proliferate and protect retinal neurons against excitotoxicity.

    abstract::The purpose of this study was to investigate whether insulin, fibroblast growth factor (FGF), and mitogen-activated protein kinase (MAPK) pathways protect retinal neurons against excitotoxicity and regulate the proliferation of Müller glia. We found that intraocular injections of insulin or FGF2 had variable effects u...


    pub_type: 杂志文章


    authors: Fischer AJ,Scott MA,Ritchey ER,Sherwood P

    更新日期:2009-11-01 00:00:00

  • Glial glutamate transport modulates dendritic spine head protrusions in the hippocampus.

    abstract::Accumulating evidence supports the idea that synapses are tripartite, whereby perisynaptic astrocytes modulate both pre- and postsynaptic function. Although some of these features have been uncovered by using electrophysiological methods, less is known about the structural interplay between synapses and glial processe...


    pub_type: 杂志文章


    authors: Verbich D,Prenosil GA,Chang PK,Murai KK,McKinney RA

    更新日期:2012-07-01 00:00:00

  • Identification of midbrain floor plate radial glia-like cells as dopaminergic progenitors.

    abstract::The floor plate (FP), a signaling center and a structure rich in radial glia-like cells, has been traditionally thought to be devoid of neurons and neuronal progenitors. However, in the midbrain, the FP contains neurons of the dopaminergic (DA) lineage that require contact with radial glia-like cells for their inducti...


    pub_type: 杂志文章


    authors: Bonilla S,Hall AC,Pinto L,Attardo A,Götz M,Huttner WB,Arenas E

    更新日期:2008-06-01 00:00:00

  • Nogo-A inhibits vascular regeneration in ischemic retinopathy.

    abstract::Nogo-A is a potent glial-derived inhibitor of axon growth in the injured CNS and acts as a negative regulator of developmental angiogenesis by inhibiting vascular endothelial cell migration. However, its function in pathological angiogenesis has never been studied after ischemic injury in the CNS. Using the mouse mode...


    pub_type: 杂志文章


    authors: Joly S,Dejda A,Rodriguez L,Sapieha P,Pernet V

    更新日期:2018-10-01 00:00:00

  • Microglia, a potential source of neurons, astrocytes, and oligodendrocytes.

    abstract::Microglia are considered the only cell population of mesodermal origin in the brain, although their role is not fully understood. The present study demonstrated that rat primary microglial cells expressed nestin, A2B5, and O4 antigens, which are markers for oligodendrocyte precursor cells. Based on these findings, we ...


    pub_type: 杂志文章


    authors: Yokoyama A,Yang L,Itoh S,Mori K,Tanaka J

    更新日期:2004-01-01 00:00:00

  • Anti-ACSA-2 defines a novel monoclonal antibody for prospective isolation of living neonatal and adult astrocytes.

    abstract::Astrocytes are the most abundant cell type of the central nervous system and cover a broad range of functionalities. We report here the generation of a novel monoclonal antibody, anti-astrocyte cell surface antigen-2 (Anti-ACSA-2). Flow cytometry, immunohistochemistry and immunocytochemistry revealed that Anti-ACSA-2 ...


    pub_type: 杂志文章


    authors: Kantzer CG,Boutin C,Herzig ID,Wittwer C,Reiß S,Tiveron MC,Drewes J,Rockel TD,Ohlig S,Ninkovic J,Cremer H,Pennartz S,Jungblut M,Bosio A

    更新日期:2017-06-01 00:00:00

  • ROCK inhibition with Y27632 activates astrocytes and increases their expression of neurite growth-inhibitory chondroitin sulfate proteoglycans.

    abstract::Inhibition of Rho-kinase (ROCK) with Y27632 stimulates sprouting by injured corticospinal tract and dorsal column tract axons, and accelerates functional recovery. However, regeneration of these axons across the glial scar was not observed. Here we examined the effects of Y27632 treatment on chondroitin sulfate proteo...


    pub_type: 杂志文章


    authors: Chan CC,Wong AK,Liu J,Steeves JD,Tetzlaff W

    更新日期:2007-03-01 00:00:00

  • The origin of remyelinating cells in the adult central nervous system: the role of the mature oligodendrocyte.

    abstract::The sequence of events by which new oligodendrocytes are generated in the adult mammalian central nervous system has not been clearly defined. Here we review old evidence that remyelinating cells can arise from the division of mature oligodendrocytes. In addition, we report the results of a tissue culture study compar...


    pub_type: 杂志文章,评审


    authors: Wood PM,Bunge RP

    更新日期:1991-01-01 00:00:00

  • The Nrf2-inducible antioxidant defense in astrocytes can be both up- and down-regulated by activated microglia:Involvement of p38 MAPK.

    abstract::The effects of microglia-conditioned medium (MCM) on the inducible Nrf2 system in astrocyte-rich cultures were investigated by determination of glutathione (GSH) levels, γglutamylcysteine ligase (γGCL) activity, the protein levels of Nrf2, Keap1, the modulatory subunit of γGCL (γGCL-M) and activated MAP kinases (ERK1/...


    pub_type: 杂志文章


    authors: Correa F,Ljunggren E,Mallard C,Nilsson M,Weber SG,Sandberg M

    更新日期:2011-05-01 00:00:00