Lipopolysaccharide-induced interleukin (IL)-4 receptor-α expression and corresponding sensitivity to the M2 promoting effects of IL-4 are impaired in microglia of aged mice

Fenn, Ashley M.; Henry, Christopher J.; Huang, Yan; Dugan, Allison; Godbout, Jonathan P.

doi:10.1016/j.bbi.2011.10.003

Cited by 198Neuroinflammation and Neurodegeneration MechanismsTryptophan and brain disordersImmune Response and Inflammation

Lipopolysaccharide-induced interleukin (IL)-4 receptor-α expression and corresponding sensitivity to the M2 promoting effects of IL-4 are impaired in microglia of aged mice

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Fenn, Ashley M., Henry, Christopher J., Huang, Yan, Dugan, Allison, Godbout, Jonathan P.·2012·Brain, Behavior, and Immunity

DOI 10.1016/j.bbi.2011.10.003PMC PMC3288757

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Abstract

In several models of aging, microglia become more inflammatory and reactive to immune challenges. For example, peripheral LPS injection causes exaggerated microglial activation associated with prolonged sickness and depressive-like behavior in aged BALB/c mice. Therefore, the purpose of this study was to determine the extent to which age-related amplified microglial activation was associated with reduced sensitivity to the anti-inflammatory and M2 promoting cytokines interleukin (IL)-10 and IL-4. In initial studies with adult mice, LPS induced a time-dependent increase in M1 and M2 mRNA profiles in microglia. Furthermore, peripheral LPS injection markedly increased surface expression of IL-4 receptor-alpha (IL-4Rα), but not IL-10 receptor-1 (IL-10R1) on microglia. In BV-2 cells, IL-4, but not IL-10, re-directed LPS-activated microglia towards an M2 phenotype. Based on these findings, comparisons of M1 and M2 activation profiles, induction of IL-4Rα, and sensitivity to IL-4 were determined in microglia from adult (3-4 mo) and aged (18-22 mo) mice. In aged microglia, LPS promoted an exaggerated and prolonged M1 and M2 profile compared to adults. Moreover, IL-4Rα protein was not increased on aged microglia following LPS injection. To determine the consequence of impaired IL-4Rα upregulation, adult and aged mice were injected with LPS and activated microglia were then isolated and treated ex vivo with IL-4. While ex vivo IL-4 induced an M2 profile in activated microglia from adult mice, activated microglia from aged mice retained a prominent M1 profile. These data indicate that activated microglia from aged mice are less sensitive to the anti-inflammatory and M2-promoting effects of IL-4.

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Aged mice fail to upregulate IL-4Rα in response to LPS and do not elicit an alternative (regulatory) immune response to ex vivo IL-4.
“Aged mice failed to upregulate IL-4Rα in response to LPS, and did not elicit an alternative (regulatory) immune response to ex vivo IL-4 (Fenn et al, 2012).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Fenn et al, 2012

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α-Tocopherol attenuates NFκB activation and pro-inflammatory cytokine production in brain and improves recovery from lipopolysaccharide-induced sickness behavior
Godbout, J. P., Berg, B. M., Krzyszton, C. P., & Johnson, R. W. (2005) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2005.08.003 · Cited by 71 · see citing works
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Lack of an effect of vitamin E on lifespan of mice
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Type 2 Diabetes Impairs Insulin Receptor Substrate-2-Mediated Phosphatidylinositol 3-Kinase Activity in Primary Macrophages to Induce a State of Cytokine Resistance to IL-4 in Association with Overexpression of Suppressor of Cytokine Signaling-3
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Endogenous expression of interleukin‐4 regulates macrophage activation and confines cavity formation after traumatic spinal cord injury
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MicroRNAs and the immune response
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Pannexin-1: the missing link?
Ahmad, S. A. (2007) · Nature reviews. Immunology · doi:10.1038/nri2110 · Cited by 2 · see citing works

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Microglial <scp>M1/M2</scp> polarization and metabolic states
Orihuela, R., McPherson, C. A., & Harry, G. J. (2016) · British Journal of Pharmacology · doi:10.1111/bph.13139 · Cited by 2,070 · see citing works
Neuroinflammation and M2 Microglia: The Good, the Bad, and the Inflamed
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Overview of General and Discriminating Markers of Differential Microglia Phenotypes
Jurga, A. M., Paleczna, M., & Kuter, K. Z. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.00198 · Cited by 1,000 · see citing works
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Review: microglia of the aged brain: primed to be activated and resistant to regulation
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Cunningham, C. (2013) · Glia · doi:10.1002/glia.22350 · Cited by 769 · see citing works
Alternatively activated microglia and macrophages in the central nervous system
Franco, R., & Fernández‐Suárez, D. (2015) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2015.05.003 · Cited by 650 · see citing works
Characterization of phenotype markers and neuronotoxic potential of polarised primary microglia in vitro
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Sequential activation of microglia and astrocyte cytokine expression precedes increased iba‐1 or GFAP immunoreactivity following systemic immune challenge
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IL-4 in the brain: a cytokine to remember
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Microglia during development and aging
Harry, G. J. (2013) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2013.04.013 · Cited by 524 · see citing works
Microglial priming and enhanced reactivity to secondary insult in aging, and traumatic CNS injury, and neurodegenerative disease
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Balancing the immune response in the brain: IL-10 and its regulation
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Microglia Priming with Aging and Stress
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Directed differentiation of human pluripotent stem cells to microglia
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TGFβ produced by IL‐10 redirected astrocytes attenuates microglial activation
Norden, D. M., Fenn, A. M., Dugan, A., & Godbout, J. P. (2014) · Glia · doi:10.1002/glia.22647 · Cited by 332 · see citing works
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IL4-driven microglia modulate stress resilience through BDNF-dependent neurogenesis
Zhang, J., Rong, P., Zhang, L., He, H., Zhou, T., Fan, Y., Mo, L., Zhao, Q., Han, Y., Li, S., et al. (2021) · Science Advances · doi:10.1126/sciadv.abb9888 · Cited by 287 · see citing works
Role of Microglia in Neurological Disorders and Their Potentials as a Therapeutic Target
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Neuroinflammation in animal models of traumatic brain injury
Chiu, C., Liao, Y.-E., Yang, L.-Y., Wang, J.-Y., Tweedie, D., Karnati, H. K., Greig, N. H., & Wang, J. (2016) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2016.06.018 · Cited by 248 · see citing works
Neurovascular unit dysfunction with blood-brain barrier hyperpermeability contributes to major depressive disorder: a review of clinical and experimental evidence
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Traumatic brain injury in aged animals increases lesion size and chronically alters microglial/macrophage classical and alternative activation states
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Immune activation promotes depression 1 month after diffuse brain injury: a role for primed microglia
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TUDCA: An Agonist of the Bile Acid Receptor GPBAR1/TGR5 With Anti‐Inflammatory Effects in Microglial Cells
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Treatment targets for M2 microglia polarization in ischemic stroke
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Retinoid X receptor activation reverses age-related deficiencies in myelin debris phagocytosis and remyelination
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NOX2 drives M1-like microglial/macrophage activation and neurodegeneration following experimental traumatic brain injury
Kumar, A., Barrett, J. P., Alvarez-Croda, D.-M., Stoica, B. A., Faden, A. I., & Loane, D. J. (2016) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2016.07.158 · Cited by 213 · see citing works
Molecular and cellular neuroinflammatory status of mouse brain after systemic lipopolysaccharide challenge: importance of CCR2/CCL2 signaling.
Cazareth, J., Guyon, A., Heurteaux, C., Chabry, J., & Petit-Paitel, A. (2014) · Journal of Neuroinflammation · doi:10.1186/1742-2094-11-132 · Cited by 206 · see citing works
IL-4 drives microglia and macrophages toward a phenotype conducive for tissue repair and functional recovery after spinal cord injury
Francos-Quijorna, I., Amo‐Aparicio, J., Martínez‐Muriana, A., & López‐Vales, R. (2016) · Glia · doi:10.1002/glia.23041 · Cited by 211 · see citing works
IL-4 Signaling Drives a Unique Arginase+/IL-1 + Microglia Phenotype and Recruits Macrophages to the Inflammatory CNS: Consequences of Age-Related Deficits in IL-4R after Traumatic Spinal Cord Injury
Fenn, A. M., Hall, J. C. E., Gensel, J. C., Popovich, P. G., & Godbout, J. P. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.1146-14.2014 · Cited by 207 · see citing works
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Microglial Phenotype and Adaptation
Eggen, B. J. L., Raj, D. D. A., Hanisch, U., & Boddeke, H. W. G. M. (2013) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-013-9490-4 · Cited by 176 · see citing works
<scp>APOE</scp>‐modulated Aβ‐induced neuroinflammation in Alzheimer's disease: current landscape, novel data, and future perspective
Tai, L. M., Ghura, S., Koster, K. P., Liakaite, V., Maienschein‐Cline, M., Kanabar, P., Collins, N., Ben‐Aissa, M., Lei, A. Z., Bahroos, N., et al. (2015) · Journal of Neurochemistry · doi:10.1111/jnc.13072 · Cited by 165 · see citing works
Integrated expression profiles of mRNA and miRNA in polarized primary murine microglia
Freilich, R. W., Woodbury, M. E., & Ikezu, T. (2013) · PLoS ONE · doi:10.1371/journal.pone.0079416 · Cited by 160 · see citing works
MicroRNA-124 as a novel treatment for persistent hyperalgesia
Willemen, H. L. D. M., Huo, X., Mao‐Ying, Q., Zijlstra, J., Heijnen, C. J., & Kavelaars, A. (2012) · Journal of Neuroinflammation · doi:10.1186/1742-2094-9-143 · Cited by 160 · see citing works
Microglia activation states and cannabinoid system: Therapeutic implications
Mecha, M., Carrillo-Salinas, F. J., Feliú, A., Mestre, L., & Guaza, C. (2016) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2016.06.011 · Cited by 160 · see citing works
MiR-9 promotes microglial activation by targeting MCPIP1
Yao, H., Ma, R., Yang, L., Hu, G., Chen, X., Duan, M., Kook, Y., Niu, F., Liao, K., Fu, M., et al. (2014) · Nature Communications · doi:10.1038/ncomms5386 · Cited by 146 · see citing works
Kynurenine pathway metabolic balance influences microglia activity: Targeting kynurenine monooxygenase to dampen neuroinflammation
Garrison, A. M., Parrott, J. M., Tuñon, A., Delgado, J., Redus, L., & O’Connor, J. C. (2018) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2018.04.019 · Cited by 152 · see citing works
Nutritional n-3 PUFAs deficiency during perinatal periods alters brain innate immune system and neuronal plasticity-associated genes
Madore, C., Nadjar, A., Delpech, J.-C., Séré, A., Aubert, A., Portal, C., Joffre, C., & Layé, S. (2014) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2014.03.021 · Cited by 144 · see citing works
Forced turnover of aged microglia induces an intermediate phenotype but does not rebalance CNS environmental cues driving priming to immune challenge
O’Neil, S. M., Witcher, K. G., McKim, D. B., & Godbout, J. P. (2018) · Acta Neuropathologica Communications · doi:10.1186/s40478-018-0636-8 · Cited by 138 · see citing works
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Infections after a traumatic brain injury: The complex interplay between the immune and neurological systems
Sharma, R., Shultz, S. R., Robinson, M. J., Belli, A., Hibbs, M. L., O'Brien, T. J., & Semple, B. D. (2019) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2019.04.034 · Cited by 137 · see citing works
Aging microglia
Antignano, I., Liu, Y., Offermann, N., & Capasso, M. (2023) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-023-04775-y · Cited by 117 · see citing works
Cognitive deficits develop 1 month after diffuse brain injury and are exaggerated by microglia-associated reactivity to peripheral immune challenge
Muccigrosso, M. M., Ford, J., Benner, B., Moussa, D., Burnsides, C., Fenn, A. M., Popovich, P. G., Lifshitz, J., Walker, F. R., Eiferman, D. S., et al. (2016) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2016.01.009 · Cited by 146 · see citing works
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cGAS knockdown promotes microglial M2 polarization to alleviate neuroinflammation by inhibiting cGAS-STING signaling pathway in cerebral ischemic stroke
Jiang, G.-L., Yang, X., Zhou, H., Long, J., Liu, B., Zhang, L.-M., & Lü, D. (2021) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2021.03.010 · Cited by 128 · see citing works
Central nervous system myeloid cells as drug targets: current status and translational challenges
Biber, K. P. H., Möller, T., Boddeke, E., & Prinz, M. (2015) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2015.14 · Cited by 111 · see citing works
Early-life enteric infections: relation between chronic systemic inflammation and poor cognition in children
Oriá, R. B., Murray‐Kolb, L. E., Scharf, R. J., Pendergast, L. L., Lang, D., Kolling, G. L., & Guerrant, R. L. (2016) · Nutrition Reviews · doi:10.1093/nutrit/nuw008 · Cited by 110 · see citing works
The aging mouse brain: cognition, connectivity and calcium
Radulescu, C. I., Cerar, V., Haslehurst, P., Kopanitsa, M. V., & Barnes, S. J. (2021) · Cell Calcium · doi:10.1016/j.ceca.2021.102358 · Cited by 105 · see citing works
Idebenone Alleviates Neuroinflammation and Modulates Microglial Polarization in LPS-Stimulated BV2 Cells and MPTP-Induced Parkinson’s Disease Mice
Yan, A., Liu, Z., Song, L., Wang, X., Zhang, Y., Wu, N., Lin, J., Liu, Y., & Liu, Z. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00529 · Cited by 103 · see citing works
IL-4 and IL-13 induce equivalent expression of traditional M2 markers and modulation of reactive oxygen species in human macrophages
Scott, T., Lewis, C., Zhu, M., Wang, C., Samuel, C. S., Drummond, G. R., & Kemp‐Harper, B. K. (2023) · Scientific Reports · doi:10.1038/s41598-023-46237-2 · Cited by 106 · see citing works
Advanced Age Alters Monocyte and Macrophage Responses
Albright, J. M., Dunn, R. C., Shults, J. A., Boe, D. M., Afshar, M., & Kovacs, E. J. (2016) · Antioxidants and Redox Signaling · doi:10.1089/ars.2016.6691 · Cited by 104 · see citing works
Neuroinflammatory In Vitro Cell Culture Models and the Potential Applications for Neurological Disorders
Peng, Y., Chu, S., Yang, Y., Zhang, Z., Pang, Z., & Chen, N. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.671734 · Cited by 102 · see citing works
Emerging roles of microglial activation and non-motor symptoms in Parkinson's disease
Doorn, K. J., Lucassen, P. J., Boddeke, H. W. G. M., Prins, M., Berendse, H. W., Drukarch, B., & van Dam, A. (2012) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2012.06.005 · Cited by 97 · see citing works
Methylene Blue Attenuates Traumatic Brain Injury-Associated Neuroinflammation and Acute Depressive-Like Behavior in Mice
Fenn, A. M., Skendelas, J. P., Moussa, D. N., Muccigrosso, M. M., Popovich, P. G., Lifshitz, J., Eiferman, D. S., & Godbout, J. P. (2014) · Journal of Neurotrauma · doi:10.1089/neu.2014.3514 · Cited by 94 · see citing works
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Increased micro-RNA 29b in the aged brain correlates with the reduction of insulin-like growth factor-1 and fractalkine ligand
Fenn, A. M., Smith, K. M., Lovett‐Racke, A. E., Guerau‐de‐Arellano, M., Whitacre, C. C., & Godbout, J. P. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.06.007 · Cited by 95 · see citing works
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The Translational Potential of Microglia and Monocyte-Derived Macrophages in Ischemic Stroke
Wicks, E. E., Ran, K. R., Kim, J. E., Xu, R., Lee, R. P., & Jackson, C. M. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.897022 · Cited by 92 · see citing works
Microglia communication: parallels between aging and Alzheimer's disease
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Microglial Phenotypic Transition: Signaling Pathways and Influencing Modulators Involved in Regulation in Central Nervous System Diseases
Li, J., Shui, X., Sun, R., Wan, L., Zhang, B., Xiao, B., & Luo, Z. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.736310 · Cited by 90 · see citing works
The reciprocal interactions between microglia and T cells in Parkinson’s disease: a double-edged sword
Xu, Y., Li, Y., Wang, C., Han, T., Liu, H., Sun, L., Hong, J., Hashimoto, M., & Wei, J. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02723-y · Cited by 88 · see citing works
Macrophages: Subtypes, Distribution, Polarization, Immunomodulatory Functions, and Therapeutics
Peng, M., Li, N., Wang, H., Li, Y., Liu, H., Luo, Y., Lang, B., Zhang, W., Li, S., Tian, L., et al. (2025) · MedComm · doi:10.1002/mco2.70304 · Cited by 95 · see citing works
Microglial priming and Alzheimer’s disease: a possible role for (early) immune challenges and epigenetics?
Hoeijmakers, L., Heinen, Y., van Dam, A.-M., Lucassen, P. J., & Korosi, A. (2016) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2016.00398 · Cited by 85 · see citing works
Sulforaphane induces Nrf2 target genes and attenuates inflammatory gene expression in microglia from brain of young adult and aged mice
Townsend, B. E., & Johnson, R. W. (2015) · Experimental Gerontology · doi:10.1016/j.exger.2015.11.004 · Cited by 75 · see citing works
Are “Resting” Microglia More “M2”?
Cherry, J. D., Olschowka, J. A., & O’Banion, M. K. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00594 · Cited by 75 · see citing works
Neuro-immune dysfunction during brain aging: new insights in microglial cell regulation
Matt, S. M., & Johnson, R. W. (2015) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2015.10.009 · Cited by 73 · see citing works
Microbiota‐microglia connections in age‐related cognition decline
Zhou, R., Qian, S., Cho, W. C. S., Zhou, J., Jin, C., Zhong, Y., Wang, J., Zhang, X., Xu, Z., Tian, M., et al. (2022) · Aging Cell · doi:10.1111/acel.13599 · Cited by 71 · see citing works
Insensitivity of astrocytes to interleukin 10 signaling following peripheral immune challenge results in prolonged microglial activation in the aged brain
Norden, D. M., Trojanowski, P. J., Walker, F. R., & Godbout, J. P. (2016) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.04.014 · Cited by 73 · see citing works
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Early morphofunctional plasticity of microglia in response to acute lipopolysaccharide
Madore, C., Joffre, C., Delpech, J.-C., Smedt, V. D., Aubert, A., Coste, L., Layé, S., & Nadjar, A. (2013) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2013.08.008 · Cited by 70 · see citing works
Dietary Luteolin Reduces Proinflammatory Microglia in the Brain of Senescent Mice
Burton, M. D., Rytych, J. L., Amin, R., & Johnson, R. W. (2016) · Rejuvenation Research · doi:10.1089/rej.2015.1708 · Cited by 69 · see citing works
Sustained anti-inflammatory effects of TGF-β1 on microglia/macrophages
Islam, A., Choudhury, M. E., Kigami, Y., Utsunomiya, R., Matsumoto, S., Watanabe, H., Kumon, Y., Kunieda, T., Yano, H., & Tanaka, J. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2017.12.022 · Cited by 69 · see citing works
Regulation of Macrophage, Dendritic Cell, and Microglial Phenotype and Function by the SOCS Proteins
McCormick, S. M., & Heller, N. M. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00549 · Cited by 67 · see citing works
Neuroprotective modulation of microglia effector functions following priming with interleukin 4 and 13: current limitations in understanding their mode-of-action
Quarta, A., Berneman, Z. N., & Ponsaerts, P. (2020) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2020.03.023 · Cited by 67 · see citing works
Calorie restriction attenuates lipopolysaccharide (LPS)-induced microglial activation in discrete regions of the hypothalamus and the subfornical organ
Radler, M. E., Hale, M. W., & Kent, S. (2013) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2013.11.014 · Cited by 64 · see citing works
mTOR-Mediated Immunometabolic Reprogramming Nanomodulators Enable Sensitive Switching of Energy Deprivation-Induced Microglial Polarization for Alzheimer’s Disease Management
Yang, F., Zhao, D., Cheng, M., Liu, Y., Chen, Z., Chang, J. K., & Dou, Y. (2023) · ACS Nano · doi:10.1021/acsnano.3c03232 · Cited by 64 · see citing works
Pathophysiological and behavioral effects of systemic inflammation in aged and diseased rodents with relevance to delirium: A systematic review
Schreuder, L., Eggen, B. J. L., Biber, K. P. H., Schoemaker, R. G., Laman, J. D., & de Rooij, S. E. (2017) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2017.01.010 · Cited by 60 · see citing works
Impact of aging immune system on neurodegeneration and potential immunotherapies
Liang, Z., Zhao, Y., Ruan, L., Zhu, L., Jin, K., Zhuge, Q., Su, D., & Zhao, Y. L. (2017) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2017.07.006 · Cited by 61 · see citing works
Complex molecular and functional outcomes of single versus sequential cytokine stimulation of rat microglia
Siddiqui, T. A., Lively, S. S., & Schlichter, L. C. (2016) · Journal of Neuroinflammation · doi:10.1186/s12974-016-0531-9 · Cited by 59 · see citing works
Methane ameliorates post-operative cognitive dysfunction by inhibiting microglia NF-κB/MAPKs pathway and promoting IL-10 expression in aged mice
Zhang, D., Li, N., Wang, Y., Lu, W., Zhang, Y., Chen, Y., Deng, X., & Yu, X. (2019) · International Immunopharmacology · doi:10.1016/j.intimp.2019.03.003 · Cited by 58 · see citing works
Neuroinflammatory processes in cognitive disorders: Is there a role for flavonoids and n-3 polyunsaturated fatty acids in counteracting their detrimental effects?
Vauzour, D., Martinsen, A., & Layé, S. (2015) · Neurochemistry International · doi:10.1016/j.neuint.2015.08.004 · Cited by 57 · see citing works
Transcriptional Profiling of Mouse Eosinophils Identifies Distinct Gene Signatures Following Cellular Activation
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Activated microglia from aged mice are less sensitive to anti-inflammatory feedback from IL-4
Fenn, A. (2011) · The Knowledge Bank (The Ohio State University)
Self-citation
Effects of Age on Microglial Responses to Cellular Stress Induced by Lipopolysacharides and Beta Amyliod
Subramaiam, H. (2011) · Universiti Putra Malaysia Institutional Repository (Universiti Putra Malaysia)
Regulation of Central Nervous System Inflammation by Anti-inflammatory Cytokines in Activated Microglia and Impairments in Aging
Dugan, A. M. (2013) · The Knowledge Bank (The Ohio State University)
Self-citation
Peripheral lipopolysaccharide (LPS) challenge promotes microglial hyperactivity in aged mice that is associated with exaggerated induction of both pro-inflammatory IL-1β and anti-inflammatory IL-10 cytokines
Henry, C. J., Huang, Y., Wynne, A. M., & Godbout, J. P. (2009) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2008.09.002 · Cited by 565 · see citing works
Self-citation
Aging sensitizes rapidly isolated hippocampal microglia to LPS ex vivo
Frank, M. G., Barrientos, R. M., Watkins, L. R., & Maier, S. F. (2010) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2010.05.022 · Cited by 109 · see citing works

Authors: Fenn, A. M., Henry, C. J., Huang, Y., Dugan, A., & Godbout, J. P.
Affiliations: The Ohio State University (US)
Corresponding author: Godbout, Jonathan P.
ORCID: Huang, Yan
Godbout, Jonathan P.
Venue: Brain, Behavior, and Immunity
Publisher: Elsevier BV
Published: 2012-07
Volume: 26
Issue: 5
Pages: 766-777
ISSN: 0889-1591 (ISSN-L)
DOI: 10.1016/j.bbi.2011.10.003
PMC: PMC3288757
OpenAlex: W1987015752
Cited by: 198
References: 85
Citations by year: 2026: 9 · 2025: 12 · 2024: 7 · 2023: 16 · 2022: 13 · 2021: 19 · 2020: 12 · 2019: 7 · 2018: 9 · 2017: 8 · 2016: 28 · 2015: 18 · 2014: 18 · 2013: 14 · 2012: 8
FWCI: 7.06
Type: journal article
Language: en
Open access: green
europepmc.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Brain Behavior and Immunity (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: Howard Hughes Medical Institute
National Institutes of Health
National Institute on Aging (R01AG033028)
Topics: Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords: microglia, aging, lipopolysaccharide, IL-4, IL-4 receptor alpha, M2 microglia, M1 microglia, IL-10, IL-10 receptor 1, microglial activation, anti-inflammatory cytokines, neuroinflammation, aged mice
MeSH terms: Aging, Animals, Cell Separation, Cells, Cultured, Flow Cytometry, Inflammation, Lipopolysaccharides, Macrophage Activation, Male, Mice, Inbred BALB C, Receptors, Cell Surface, RNA, Interleukin-4, Microglia, Mice, Interleukin-4 Receptor alpha Subunit, Interleukin-10 Receptor alpha Subunit, Real-Time Polymerase Chain Reaction

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Lipopolysaccharide-induced interleukin (IL)-4 receptor-α expression and corresponding sensitivity to the M2 promoting effects of IL-4 are impaired in microglia of aged mice

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