Cited by 1,645Neuroinflammation and Neurodegeneration MechanismsTryptophan and brain disordersInflammasome and immune disorders

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Microglia as a source and target of cytokines

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Hanisch, Uwe‐Karsten·2002·Glia

DOI 10.1002/glia.10161

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Abstract

Cytokines constitute a significant portion of the immuno‐ and neuromodulatory messengers that can be released by activated microglia. By virtue of potent effects on resident and invading cells, microglial cyto‐ and chemokines regulate innate defense mechanisms, help the initiation and influence the type of immune responses, participate in the recruitment of leukocytes to the CNS, and support attempts of tissue repair and recovery. Microglia can also receive cyto‐ and chemokine signals as part of auto‐ and paracrine communications with astrocytes, neurons, the endothelium, and leukocyte infiltrates. Strong responses and modulatory influences can be demonstrated, adding to the emerging view that microglial behavior is highly dependent on the (cytokine) environment and that reactions to a challenge may vary with the stimulation context. In principle, microglial activation aims at CNS protection. However, failed microglial engagement due to excessive or sustained activation could significantly contribute to acute and chronic neuropathologies. Dysregulation of microglial cytokine production could thereby promote harmful actions of the defense mechanisms, result in direct neurotoxicity, as well as disturb neural cell functions as they are sensitive to cytokine signaling. GLIA 40:140–155, 2002. © 2002 Wiley‐Liss, Inc.

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β-Arrestin 2-dependent activation of ERK1/2 is required for ADP-induced paxillin phosphorylation at Ser83 and microglia chemotaxis
Lee, S.-H., Hollingsworth, R. J., Kwon, H., Lee, N., & Chung, C. Y. (2012) · Glia · doi:10.1002/glia.22355 · Cited by 31
“…into a motile ameboid form after pathological stimuli and migrates toward lesion sites, where they become activated and exert their neuroprotective effects such as secreting a variety of substances and clearance of cell debris (Hanisch, 2002; Kreutzberg, 1996; Stence et al., 2001; Thomas, 1999).”
Background
Up-regulation of platelet-activating factor synthases and its receptor in spinal cord contribute to development of neuropathic pain following peripheral nerve injury
Okubo, M., Yamanaka, H., Kobayashi, K., Kanda, H., Dai, Y., & Noguchi, K. (2012) · Molecular Pain · doi:10.1186/1744-8069-8-8 · Cited by 31
Implications of organophosphate pesticides on brain cells and their contribution toward progression of Alzheimer's disease
Yadav, B., Kaur, S., Yadav, A., Verma, H., Kar, S., Sahu, B. K., Pati, K. R., Sarkar, B., Dhiman, M., & Mantha, A. K. (2024) · Journal of Biochemical and Molecular Toxicology · doi:10.1002/jbt.23660 · Cited by 34
The potential role of glial cells in driving the prion-like transcellular propagation of tau in tauopathies
Amro, Z., Yool, A. J., & Collins‐Praino, L. E. (2021) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2021.100242 · Cited by 39
“Interestingly, during the progression of AD pathology, reactive microglial phenotypes are shown to be skewed to an M1 phenotype, releasing more pro-inflammatory cytokines and nitric oxide (Hanisch, 2002).”
Background
Walnut-Associated Fatty Acids Inhibit LPS-Induced Activation of BV-2 Microglia
Carey, A. N., Fisher, D. R., Bielinski, D. F., Cahoon, D. S., & Shukitt‐Hale, B. (2019) · Inflammation · doi:10.1007/s10753-019-01113-y · Cited by 30
Caspases orchestrate microglia instrumental functions
Shen, X., Venero, J. L., Joseph, B., & Burguillos, M. Á. (2018) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2018.09.007 · Cited by 31
Redox tuning of Ca2+ signaling in microglia drives glutamate release during hypoxia
Socodato, R., Portugal, C. C., Rodrigues, A., Henriques, J. F., Rodrigues, C., Figueira, C., & Relvas, J. B. (2018) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.02.036 · Cited by 31
ASK1 modulates the expression of microRNA Let7A in microglia under high glucose in vitro condition
Song, J., & Lee, J. E. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00198 · Cited by 30
“Thus, the relationship between Let-7A and ASK1 could be a novel target for enhancing the beneficial function of microglia in central nervous system (CNS) disorders.”
BackgroundInfluential
Peripheral tumors alter neuroinflammatory responses to lipopolysaccharide in female rats
Pyter, L., Bih, S. E. M., Sattar, H., & Prendergast, B. J. (2014) · Brain Research · doi:10.1016/j.brainres.2014.01.012 · Cited by 30
“Microglia are the main sources of de novo cytokine production in the brain, although astrocytes, neurons, and endothelial cells may also contribute (Hanisch, 2002; Kim and de Vellis, 2005).”
Inferring metabolic networks using the Bayesian adaptive graphical lasso with informative priors
Peterson, C. B., Vannucci, M., Karakas, C., Choi, W. T., Ma, L.-H., & Maletić-Savatić, M. (2013) · Statistics and its Interface · doi:10.4310/sii.2013.v6.n4.a12 · Cited by 30
“At this time, microglia secrete cytokines, which act as molecular signals to alarm other cellular players in the niche of the impending danger, resulting in inflammation [20, 26].”
HIV-1 Tat Protein Increases Microglial Outward K+ Current and Resultant Neurotoxic Activity
Liu, J., Xu, P., Collins, C., Liu, H., Zhang, J., Keblesh, J. P., & Xiong, H. (2013) · PLoS ONE · doi:10.1371/journal.pone.0064904 · Cited by 28
Melatonin reduces median nerve injury‐induced mechanical hypersensitivity via inhibition of microglial p38 mitogen‐activated protein kinase activation in rat cuneate nucleus
Chiang, R. P., Huang, C., & Tsai, Y. (2012) · Journal of Pineal Research · doi:10.1111/jpi.12029 · Cited by 28
“Recent work demonstrated that activated microglia released signal mediators, such as pro-inflammatory cytokines (IL-1b, IL-6, and TNF-a), cyclooxygenase-2 (COX2), and inducible nitric oxide synthase (iNOS), and these mediators appeared to contribute to different features of pathological pain [4, 40, 41].”
Background
TNFα and IL-1β are mediated by both TLR4 and Nod1 pathways in the cultured HAPI cells stimulated by LPS
Zheng, W., Zheng, X.-X., Liu, S., Ouyang, H., Levitt, R., Candiotti, K., & Hao, S.-L. (2012) · Biochemical and Biophysical Research Communications - BBRC · doi:10.1016/j.bbrc.2012.03.068 · Cited by 30
“Microglial cytokines also seems to be critical in boosting chemokineinduced glutamate release from astrocytes [28].”
Background
C1q/TNF-related protein 4 restores leptin sensitivity by downregulating NF-κB signaling and microglial activation
Ye, L., Jia, G., Li, Y., Wang, Y., Chen, H., Yu, L., & Wu, D. (2021) · Journal of Neuroinflammation · doi:10.1186/s12974-021-02167-2 · Cited by 29
Costunolide Plays an Anti-Neuroinflammation Role in Lipopolysaccharide-Induced BV2 Microglial Activation by Targeting Cyclin-Dependent Kinase 2
Liu, Y.-C., Feng, N., Li, W., Tu, P., Chen, J., Han, J., & Zeng, K. (2020) · Molecules · doi:10.3390/molecules25122840 · Cited by 36
“However, microglia can be over-activated under continuous noxious stimuli, resulting in inflammatory mediator release as well as further neuronal damage [4,5].”
Background
Reversal of prolonged obesity-associated cerebrovascular dysfunction by inhibiting microglial Tak1
Shen, Q. X., Chen, Z., Zhao, F., Pan, S., Zhang, T., Cheng, X., Zhang, L., Zhang, S., Qi, J., Li, J., et al. (2020) · Nature Neuroscience · doi:10.1038/s41593-020-0642-6 · Cited by 38
Tumor Necrosis Factor-α-Mediated Metaplastic Inhibition of LTP Is Constitutively Engaged in an Alzheimer's Disease Model
Singh, A., Jones, O. D., Mockett, B. G., Ohline, S. M., & Abraham, W. C. (2019) · Journal of Neuroscience · doi:10.1523/jneurosci.1492-19.2019 · Cited by 40
Neuroinflammation in the pathogenesis of axonal Charcot-Marie-Tooth disease caused by lack of GDAP1
Fernández‐Lizarbe, S., Civera-Tregón, A., Cantarero, L., Herrer, I., Juárez, P., Hoenicka, J., & Palau, F. (2019) · Experimental Neurology · doi:10.1016/j.expneurol.2019.113004 · Cited by 32
Ferulic acid suppresses expression of tryptophan metabolic key enzyme indoleamine 2, 3-dioxygenase via NFκB and p38 MAPK in lipopolysaccharide-stimulated microglial cells
Koshiguchi, M., Komazaki, H., Hirai, S., & Egashira, Y. (2017) · Bioscience Biotechnology and Biochemistry · doi:10.1080/09168451.2016.1274636 · Cited by 36
Involvement of p38 MAPK activation mediated through AT1 receptors on spinal astrocytes and neurons in angiotensin II- and III-induced nociceptive behavior in mice
Nemoto, W., Ogata, Y., Nakagawasai, O., Yaoita, F., Tadano, T., & Tan–No, K. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2015.07.022 · Cited by 31
“Hanisch, 2002).”
Therapeutic concentration of lithium stimulates complement C3 production in dendritic cells and microglia via GSK‐3 inhibition
Yu, Z.-Q., Ono, C. T., Aiba, S., Kikuchi, Y., Sora, I., Matsuoka, H., & Tomita, H. (2015) · Glia · doi:10.1002/glia.22749 · Cited by 29
“…and microglia, play pivotal roles in the innate immune system in both the brain and peripheral tissues via their migratory and phagocytic functions, or by releasing cytokines and complement components (Austyn, 1996; Banchereau et al., 2000; Becher et al., 2000; Gasque et al., 2000; Hanisch, 2002).”
Background
Copper modulates the phenotypic response of activated BV2 microglia through the release of nitric oxide
Rossi-George, A., Guo, C.-J., Oakes, B. L., & Gow, A. (2012) · Nitric oxide · doi:10.1016/j.niox.2012.07.002 · Cited by 29
“Microglia represent one effecter arm of the CNS innate immunity as they are involved in pathogen recognition [3] and are the first to respond to help protect the CNS from invading pathogens and from the damaging consequences of neural trauma and disease.”
Background
RETRACTED ARTICLE: Dose-dependent changes in neuroinflammatory and arachidonic acid cascade markers with synaptic marker loss in rat lipopolysaccharide infusion model of neuroinflammation
Kellom, M., Basselin, M., Keleshian, V. L., Chen, M., Rapoport, S. I., & Rao, J. S. (2012) · BMC Neuroscience · doi:10.1186/1471-2202-13-50 · Cited by 27
Retracted
Postoperative Delirium in Neurosurgical Patients: Recent Insights into the Pathogenesis
Xu, Y., Ma, Q., Du, H., Yang, C., & Lin, G. (2022) · Brain Sciences · doi:10.3390/brainsci12101371 · Cited by 28
“Activated microglial cells have long been considered the main source of proinflammatory factors such as cytokines, eicosanoids, complement factors, excitatory amino acids, reactive oxygen radicals, and nitric oxide [48,54].”
Background
In Vitro Methodologies to Study the Role of Advanced Glycation End Products (AGEs) in Neurodegeneration
Chrysanthou, M., Estruch, I. M., Rietjens, I. M. C. M., Wichers, H. J., & Hoppenbrouwers, T. (2022) · Nutrients · doi:10.3390/nu14020363 · Cited by 31
The Association of Blood-Based Inflammatory Factors IL-1β, TGF-β and CRP with Cognitive Function in Alzheimer’s Disease and Mild Cognitive Impairment
Park, J. K., Lee, K. J., Kim, J. Y., & Kim, H. (2021) · Psychiatry Investigation · doi:10.30773/pi.2020.0205 · Cited by 36
Alzheimers Disease: New Concepts on the Role of Autoimmunity and NLRP3 Inflammasome in the Pathogenesis of the Disease
Severini, C., Barbato, C., Certo, M. G. D., Gabanella, F., Petrella, C., Stadio, A. D., VINCENTIIS, M. D., Polimeni, A., Ralli, M., & Greco, A. (2020) · Current Neuropharmacology · doi:10.2174/1570159x18666200621204546 · Cited by 34
6-Methoxyflavanone abates cisplatin-induced neuropathic pain apropos anti-inflammatory mechanisms: A behavioral and molecular simulation study
Akbar, S., Subhan, F., Shahid, M. M., Wadood, A., Shahbaz, N., Farooq, U., Ayaz, M., & Raziq, N. (2020) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2020.172972 · Cited by 35
Microglial density determines the appearance of pathological neovascular tufts in oxygen-induced retinopathy
Xu, W.-Q., Hu, Z., Lv, Y., Dou, G., Zhang, Z., Wang, H.-Y., & Wang, Y.-S. (2018) · Cell and Tissue Research · doi:10.1007/s00441-018-2847-5 · Cited by 28
Cdk5 contributes to inflammation-induced thermal hyperalgesia mediated by the p38 MAPK pathway in microglia.
Fang-Hu, Zhang, H.-H., Yang, B., Huang, J.-L., Shun, J., Kong, F., Peng-Xu, Chen, Z.-G., & Lu, J. (2015) · Brain Research · doi:10.1016/j.brainres.2015.01.056 · Cited by 28
Neuropeptide Y system in the retina: From localization to function
Santos-Carvalho, A., Ambrósio, A. F., & Cavadas, C. (2015) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2015.03.001 · Cited by 34
“Microglia cells play a dual role in the retina, as in the brain, releasing both pro-inflammatory cytokines and neurotrophic factors (Butovsky et al., 2005; Hanisch, 2002).”
Pharmacologic heat shock protein 70 induction confers cytoprotection against inflammation in glio-vascular cells
Kacimi, R., & Yenari, M. (2015) · Glia · doi:10.1002/glia.22811 · Cited by 28
“This model could be said to model the aspects of brain ischemia/trauma, neuroinflamma- tion, and sepsis where injurious or inflammatory stimuli activate immune cells and lead to BBB disruption (Alvarez et al., 1996; Hanisch, 2002; Lehnardt, 2010).”
Method
Neuropeptide Y protects cerebral cortical neurons by regulating microglial immune function
Li, Q.-J., Dong, C.-Z., Li, W.-L., Bu, W., Wu, J., & Zhao, W.-Q. (2014) · Neural Regeneration Research · doi:10.4103/1673-5374.133140 · Cited by 28
“Microglial activation is a key step in the inflammatory process in the central nervous system (Hanisch, 2002; Kaur et al., 2010; Kraft and Harry, 2011).”
Background
Reversal of Established Traumatic Brain Injury-Induced, Anxiety-Like Behavior in Rats after Delayed, Post-Injury Neuroimmune Suppression
Rodgers, K. M., Deming, Y. K., Bercum, F. M., Chumachenko, S. Y., Wieseler, J. L., Johnson, K. W., Watkins, L. R., & Barth, D. S. (2013) · Journal of Neurotrauma · doi:10.1089/neu.2013.3090 · Cited by 33
Pro-inflammatory cytokines predominate in the brains of dogs with visceral leishmaniasis: A natural model of neuroinflammation during systemic parasitic infection
de Melo, G. D., Seraguci, T. F., Schweigert, A., Silva, J. E. S., Grano, F. G., Peiró, J. R., de Lima, V. M. F., & Machado, G. F. (2012) · Veterinary Parasitology · doi:10.1016/j.vetpar.2012.11.002 · Cited by 25
The Immune System and the Developing Brain
Schwarz, J. M., & Bilbo, S. D. (2011) · Colloquium Series on The Developing Brain · doi:10.4199/c00045ed1v01y201110dbr004 · Cited by 25
Current Symptomatic and Disease-Modifying Treatments in Multiple System Atrophy
Mészáros, L., Hoffmann, A., Wihan, J., & Winkler, J. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21082775 · Cited by 32
A3 adenosine receptor agonist attenuates neuropathic pain by suppressing activation of microglia and convergence of nociceptive inputs in the spinal dorsal horn
Terayama, R., Tabata, M., Maruhama, K., & Iida, S. (2018) · Experimental Brain Research · doi:10.1007/s00221-018-5377-1 · Cited by 34
Orientin and neuropathic pain in rats with spinal nerve ligation
Guo, D., Hu, X., Zhang, H., Lu, C., Cui, G., & Luo, X. (2018) · International Immunopharmacology · doi:10.1016/j.intimp.2018.03.013 · Cited by 26
Characterization of inflammatory markers and transcriptome profiles of differentially activated embryonic stem cell‐derived microglia
Beins, E. C., Ulas, T., Ternes, S., Neumann, H., Schultze, J. L., & Zimmer, A. (2016) · Glia · doi:10.1002/glia.22979 · Cited by 25
“Microglia, the resident immune cells of the CNS, arehighly adaptive cells with multiple roles in brain physiology and neuroinflammation (Hanisch and Kettenmann, 2007).”
Background
Serum metabolites from walnut-fed aged rats attenuate stress-induced neurotoxicity in BV-2 microglial cells
Fisher, D. R., Poulose, S. M., Bielinski, D. F., & Shukitt‐Hale, B. (2014) · Nutritional Neuroscience · doi:10.1179/1476830514y.0000000150 · Cited by 31
Mechanisms and consequences of microglial responses to peripheral axotomy
Aldskogius, H. (2011) · Frontiers in Bioscience-Scholar · doi:10.2741/192 · Cited by 27
Dynamics of neuron-glia interplay upon exposure to unconjugated bilirubin
Silva, S. L., Osório, C., Vaz, A. R., Barateiro, A. P., Falcão, A. S., Silva, R. F. M., & Brites, D. M. T. O. (2011) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2011.07200.x · Cited by 23
Microglia–T cell conversations in brain cancer progression
Mirzaei, R., & Yong, V. W. (2022) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2022.08.006 · Cited by 35
CCR4 Antagonist (C021) Administration Diminishes Hypersensitivity and Enhances the Analgesic Potency of Morphine and Buprenorphine in a Mouse Model of Neuropathic Pain
Bogacka, J., Ciapała, K., Pawlik, K., Kwiatkowski, K., Dobrogowski, J., Przeklasa-Muszyńska, A., & Mika, J. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01241 · Cited by 32
“Importantly, transmembrane cytokine receptors expressed by neurons and microglia/macrophages are essential for cell activation, which makes them promising targets for pharmacological interventions (12).”
Background
Interleukin-6 Derived from the Central Nervous System May Influence the Pathogenesis of Experimental Autoimmune Encephalomyelitis in a Cell-Dependent Manner
Sanchís, P., Fernández‐Gayol, O., Comes, G., Escrig, A., Giralt, M., Palmiter, R. D., & Hidalgo, J. (2020) · Cells · doi:10.3390/cells9020330 · Cited by 27
Activation of microglia in acute hippocampal slices affects activity-dependent long-term potentiation and synaptic tagging and capture in area CA1
Raghuraman, R., Karthikeyan, A., Wei, W. L., Dheen, S. T., & Sajikumar, S. (2019) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2019.107039 · Cited by 32
3D Organotypic Spinal Cultures: Exploring Neuron and Neuroglia Responses Upon Prolonged Exposure to Graphene Oxide
Musto, M., Rauti, R., Rodrigues, A. F., Bonechi, E., Ballerini, C., Kostarelos, K., & Ballerini, L. (2019) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2019.00001 · Cited by 49
“In a small set of experiments an inflammatory response was induced (Hanisch, 2002), by incubating organotypic slices, for 6 h, with a cocktail of the following mouse recombinant cytokines: TNF-α (R&D Systems, #210-TA/CF), IL-1β (R&D Systems, #M15330), GM-CSF (R&D Systems, #P04141), 10 ng/mL each,…”
Sex Differences in Early Postnatal Microglial Colonization of the Developing Rat Hippocampus Following a Single-Day Alcohol Exposure
Ruggiero, M., Boschen, K., Roth, T. L., & Klintsova, A. (2017) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-017-9774-1 · Cited by 26
“…identification of a pathogen, microglia respond by changing their phenotypic activation state to increase production of proinflammatory cytokines (Kreutzberg 1996; Hanisch 2002; Town et al. 2005; Neumann et al. 2008; Kane et al. 2011; McClain et al. 2011; Topper et al. 2015; Boschen et al. 2016).”
Background
Pain modulation from the brain during diabetic neuropathy: Uncovering the role of the rostroventromedial medulla
Silva, M., Costa‐Pereira, J. T., Martins, D., & Tavares, I. (2016) · Neurobiology of Disease · doi:10.1016/j.nbd.2016.10.002 · Cited by 29
Learned helplessness activates hippocampal microglia in rats: A potential target for the antidepressant imipramine
Iwata, M., Ishida, H., Kaneko, K., & Shirayama, Y. (2016) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2016.10.005 · Cited by 31
Identification of antitumor lignans from the seeds of morning glory (Pharbitis nil).
Kim, K. H., Woo, K.-W., Moon, E., Choi, S.-U., Kim, S., Choi, S., Son, M., & Lee, K. (2014) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf501470k · Cited by 26
Interaction of inflammatory and anti-inflammatory responses in microglia by Staphylococcus aureus-derived lipoteichoic acid
Huang, B.-R., Tsai, C.-F., Lin, H.-Y., Tseng, W., Huang, S.-S., Wu, C., Lin, C., Yeh, W., & Lu, D. (2013) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2013.03.004 · Cited by 26
Effects of LPS on P2X3 receptors of trigeminal sensory neurons and macrophages from mice expressing the R192Q Cacna1a gene mutation of familial hemiplegic migraine-1
Franceschini, A., Hullugundi, S. K., van den Maagdenberg, A. M., Nistri, A., & Fabbretti, E. (2013) · Purinergic Signalling Purinergic Signalling · doi:10.1007/s11302-012-9328-1 · Cited by 26
Contributions of Microglia to Structural Synaptic Plasticity
Kim, K. H., Son, S. M., & Mook‐Jung, I. (2013) · Journal of Experimental Neuroscience · doi:10.4137/jen.s11269 · Cited by 25
The critical role of spinal ceramide in the development of partial sciatic nerve ligation-induced neuropathic pain in mice.
Kobayashi, Y., Kiguchi, N., Maeda, T., Ozaki, M., & Kishioka, S. (2012) · Biochemical and Biophysical Research Communications - BBRC · doi:10.1016/j.bbrc.2012.03.153 · Cited by 26
Allotransplanted Neurons Used to Repair Peripheral Nerve Injury Do Not Elicit Overt Immunogenicity
Liu, W., Ren, Y., Bossert, A., Wang, X., Dayawansa, S., Tong, J., He, X.-S., Smith, D. H., Gelbard, H., & Huang, J. H. (2012) · PLoS ONE · doi:10.1371/journal.pone.0031675 · Cited by 26
“. Th1 response is associated with transplant rejection, while a Th2 response may contribute to tolerance and stable graft survival”
Background
Sustained type I interferon signaling after human immunodeficiency virus type 1 infection of human iPSC derived microglia and cerebral organoids
Boreland, A. J., Stillitano, A. C., Lin, H., Abbo, Y., Hart, R. P., Jiang, P., Pang, Z. P., & Rabson, A. B. (2024) · iScience · doi:10.1016/j.isci.2024.109628 · Cited by 30
“82 83–85 Cytokine/chemokine analysis of the supernatant of HIV-1-infected microglia identiﬁed the secretion of M-CSF and IP-10/CXCL10 (Figure 2F).”
Regulation of microglial activation in stroke in aged mice: a translational study
Ngwa, C., Mamun, A. A., Qi, S., Sharmeen, R., Xu, Y., & Liu, F. (2022) · Aging · doi:10.18632/aging.204216 · Cited by 23
Diverse inflammatory threats modulate astrocytes Ca2+ signaling via connexin43 hemichannels in organotypic spinal slices
Panattoni, G., Amoriello, R., Memo, C., Thalhammer, A., Ballerini, C., & Ballerini, L. (2021) · Molecular Brain · doi:10.1186/s13041-021-00868-6 · Cited by 30
MicroRNAs in the Spinal Microglia Serve Critical Roles in Neuropathic Pain
Tang, S., Jing, H., Song, F., Huang, H., Li, W., Xie, G., & Zhou, J. (2020) · Molecular Neurobiology · doi:10.1007/s12035-020-02102-1 · Cited by 25
Extracellular Vesicles Secreted in Response to Cytokine Exposure Increase Mitochondrial Oxygen Consumption in Recipient Cells
Russell, A. E., Jun, S., Sarkar, S., Geldenhuys, W. J., Lewis, S. E., Rellick, S. L., & Simpkins, J. W. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00051 · Cited by 27
“Extracellular Aβ plaques activate microglia, prompting secretion of immunomodulatory molecules, including tumor necrosis factor-alpha (TNF-α; Hanisch, 2002).”
Background
Autophagy resolves early retinal inflammation in Igf1 -deficient mice
Arroba, A. I., la Rosa, L. R., Murillo‐Cuesta, S., Vaquero-Villanueva, L., Hurlé, J. M., Varela‐Nieto, I., & Valverde, Á. M. (2016) · Disease Models & Mechanisms · doi:10.1242/dmm.026344 · Cited by 27
“In the CNS, microglial cells comprise the resident phagocyte population, and have important roles in immune surveillance as well as in neuronal homeostasis (Hanisch, 2002; Streit, 2002, 2005).”
Background
Regulation of neuronal excitability by release of proteins from glial cells
Igelhorst, B. A., Niederkinkhaus, V., Karus, C., Lange, M. D., & Dietzel, I. D. (2015) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2014.0194 · Cited by 27
SCH58261 the Selective Adenosine A2A Receptor Blocker Modulates Ischemia Reperfusion Injury Following Bilateral Carotid Occlusion: Role of Inflammatory Mediators
Mohamed, R. A., Agha, A. M., & Nassar, N. N. (2011) · Neurochemical Research · doi:10.1007/s11064-011-0640-x · Cited by 28
Freewheel Training Alters Mouse Hippocampal Cytokines
Pervaiz, N., & Hoffman‐Goetz, L. (2011) · International Journal of Sports Medicine · doi:10.1055/s-0031-1279780 · Cited by 25
Src signaling involvement in Japanese encephalitis virus-induced cytokine production in microglia.
Chen, C.-J., Ou, Y., Chang, C.-Y., Pan, H.-C., Lin, S.-Y., Liao, S.-L., Raung, S., Chen, S.-Y., & Chang, C.-J. (2011) · Neurochemistry International · doi:10.1016/j.neuint.2011.02.022 · Cited by 25
How the gut microbiota impacts neurodegenerative diseases by modulating CNS immune cells
Schaible, P., Henschel, J., & Erny, D. (2025) · Journal of Neuroinflammation · doi:10.1186/s12974-025-03371-0 · Cited by 32
“During disease progression, microglia continuously produce neurotoxic cytokines such as interleukin (IL)-1β, IL-8, tumor necrosis factor alpha (TNF-α) and reactive oxygen species (ROS) [54].”
Neuroimaging, Urinary, and Plasma Biomarkers of Treatment Response in Huntington's Disease: Preclinical Evidence with the p75NTR Ligand LM11A-31
Simmons, D. A., Mills, B. D., Butler, R. R., Kuan, J., McHugh, T. L. M., Akers, C. S., Zhou, J., Syriani, W., Goubran, M., Zeineh, M., et al. (2021) · Neurotherapeutics · doi:10.1007/s13311-021-01023-8 · Cited by 28
Pretreatment with resveratrol ameliorate trigeminal neuralgia by suppressing matrix metalloproteinase-9/2 in trigeminal ganglion
Yin, Y.-L., Guo, R., Shao, Y., Ge, M., Chen, M., Cao, L., Yang, Y., & Hu, L. (2019) · International Immunopharmacology · doi:10.1016/j.intimp.2019.04.014 · Cited by 34
Computational modeling of cytokine signaling in microglia
Anderson, W. D., Makadia, H. K., Greenhalgh, A. D., Schwaber, J. S., David, S., & Vadigepalli, R. (2015) · Molecular BioSystems · doi:10.1039/c5mb00488h · Cited by 25
The role of glutamate excitotoxicity and neuroinflammation in depression and suicidal behavior: focus on microglia cells
Serafini, G., Amore, M., & Rihmer, Z. (2015) · Neuroimmunology and Neuroinflammation · doi:10.4103/2347-8659.157955 · Cited by 27
Retinal pigment epithelium cells alter the pro‐inflammatory response of retinal microglia to TLR ‐3 stimulation
Klettner, A., Hamann, T., Schlüter, K., Lucius, R., & Roider, J. B. (2014) · Acta Ophthalmologica · doi:10.1111/aos.12472 · Cited by 29
“Activatedmicroglia may secrete a variety of cytokines, such as IL-1ß, IL-10, TNFaor IL-6 (Hanisch 2002).”
Background

Authors: Hanisch, U.
Affiliations: Max Delbrück Center (DE)
Corresponding author: Hanisch, Uwe‐Karsten
Venue: Glia
Publisher: Wiley
Published: 2002-10-04
Volume: 40
Issue: 2
Pages: 140-155
ISSN: 0894-1491 (ISSN-L)
1098-1136
DOI: 10.1002/glia.10161
OpenAlex: W2090804892
Cited by: 1,645
References: 0
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FWCI: 4.22
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Glia (publishedVersion)
PubMed (publishedVersion)
Funders: Deutsche Forschungsgemeinschaft
Topics: Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
Keywords: microglia, cytokines, chemokines, microglial activation, neuroinflammation, neuroprotection, astrocyte-microglia interaction, tissue repair, neurotoxicity, neuropathology, innate immunity
MeSH terms: Animals, Cell Communication, Endocrine System, Endothelium, Vascular, Humans, Neuroglia, Neurons, Cytokines, Microglia

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Microglia as a source and target of cytokines

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