Bone marrow-derived macrophages from aged rats are more responsive to inflammatory stimuli
Open accessAbstract
BACKGROUND: Lipopolysaccharide (LPS) and interferon-γ (IFNγ) increase expression of tumour necrosis factor-α (TNFα) that characterizes the M1 activation state of macrophages. Whereas it is accepted that the immune system undergoes changes with age, there is inconsistency in the literature with respect to the impact of age on the response of macrophages to inflammatory stimuli. Here, we investigate the effect of age on the responsiveness of bone marrow-derived macrophages (BMDMs) to LPS and IFNγ. The context for addressing this question is that macrophages, which infiltrate the brain of aged animals, will encounter the neuroinflammatory environment that has been described with age. METHODS: Brain tissue, prepared from young and aged rats, was assessed for expression of inflammatory markers by PCR and for evidence of infiltration of macrophages by flow cytometry. BMDMs were prepared from the long bones of young and aged rats, maintained in culture for 8 days and incubated in the presence or absence of LPS (100 ng/ml) or IFNγ (50 ng/ml). Cells were harvested and assessed for mRNA expression of markers of M1 activation including TNFα and NOS2, or for expression of IFNγR1 and TLR4 by western immunoblotting. To assess whether BMDMs induced glial activation, mixed glial cultures were incubated in the presence of conditioned media obtained from unstimulated BMDMs of young and aged rats and evaluated for expression of inflammatory markers. RESULTS: Markers associated with M1 activation were expressed to a greater extent in BMDMs from aged rats in response to LPS and IFNγ, compared with cells from young rats. The increased responsiveness was associated with increases in IFNγ receptor (IFNγR) and Toll-like receptor 4 (TLR4). The data show that conditioned media from BMDMs of aged rats increased the expression of pro-inflammatory mediators in glial cells. Significantly, there was an age-related increase in macrophage infiltration into the brain, and this was combined with increased expression of IFNγ and the Toll-like receptor 4 agonist, high-mobility group protein B1 (HMGB1). CONCLUSION: Exposure of infiltrating macrophages to the inflammatory microenvironment that develops in the brain with age is likely to contribute to a damaging cascade that negatively impacts neuronal function.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Other studies suggest that macrophages contribute to microglial activation, exacerbating pathogenic neuroinflammation.
“while others suggest that macrophages contribute to microglial activation, exacerbating pathogenic neuroinflammation.18,19”
From TET2-mutant myeloid cells mitigate Alzheimer’s disease progression via CNS infiltration and enhanced phagocytosis in mice (2025) · cites this paper as [18]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Alternative activation of macrophages
Gordon, S. (2003) · Nature Reviews Immunology · doi:10.1038/nri978 · Cited by 6,189 · see citing works
Taganov, K. D., Boldin, M. P., Chang, K.-J., & Baltimore, D. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0605298103 · Cited by 4,317 · see citing works
Alternative activation of macrophages: mechanism and functions
Gordon, S., & Martinez, F. O. (2010) · Immunity · doi:10.1016/j.immuni.2010.05.007 · Cited by 4,197 · see citing works
Stein, M., Keshav, S., Harris, N., & Gordon, S. (1992) · The Journal of experimental medicine · doi:10.1084/jem.176.1.287 · Cited by 1,960 · see citing works
The many faces of macrophage activation
Mosser, D. M. (2003) · Journal of Leukocyte Biology · doi:10.1189/jlb.0602325 · Cited by 1,902 · see citing works
Simard, A. R., Soulet, D., Gowing, G., Julien, J.-P., & Rivest, S. (2006) · Neuron · doi:10.1016/j.neuron.2006.01.022 · Cited by 1,265 · see citing works
Infiltrating monocytes trigger EAE progression, but do not contribute to the resident microglia pool
Ajami, B., Bennett, J. L., Krieger, C., McNagny, K. M., & Rossi, F. M. V. (2011) · Nature Neuroscience · doi:10.1038/nn.2887 · Cited by 1,061 · see citing works
El Khoury, J., Toft, M., Hickman, S. E., Means, T. K., Terada, K., Geula, C., & Luster, A. D. (2007) · Nature Medicine · doi:10.1038/nm1555 · Cited by 915 · see citing works
Henry, C. J., Huang, Y., Wynne, A., Hanke, M., Himler, J., Bailey, M. T., Sheridan, J. F., & Godbout, J. P. (2008) · Journal of Neuroinflammation · doi:10.1186/1742-2094-5-15 · Cited by 678 · see citing works
Cutting edge: impaired toll-like receptor expression and function in aging
Renshaw, M., Rockwell, J., Engleman, C., Gewirtz, A., Katz, J., & Sambhara, S. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.169.9.4697 · Cited by 626 · see citing works
Aging-induced type I interferon response at the choroid plexus negatively affects brain function
Baruch, K., Deczkowska, A., David, E., Castellano, J. M., Miller, O., Kertser, A., Berkutzki, T., Barnett-Itzhaki, Z., Bezalel, D., Wyss-Coray, T., et al. (2014) · Science · doi:10.1126/science.1252945 · Cited by 615 · see citing works
Murphy, Á. C., Lalor, S. J., Lynch, M. A., & Mills, K. H. G. (2010) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2010.01.014 · Cited by 467 · see citing works
Self-citationInnate immunity in aging: impact on macrophage function
Plowden, J., Renshaw‐Hoelscher, M., Engleman, C., Katz, J. M., & Sambhara, S. R. (2004) · Aging Cell · doi:10.1111/j.1474-9728.2004.00102.x · Cited by 430 · see citing works
Alternative activation of macrophages: immune function and cellular biology
Varin, A., & Gordon, S. (2009) · Immunobiology · doi:10.1016/j.imbio.2008.11.009 · Cited by 361 · see citing works
The Multifaceted Profile of Activated Microglia
Lynch, M. A. (2009) · Molecular Neurobiology · doi:10.1007/s12035-009-8077-9 · Cited by 323 · see citing works
Self-citationRegulation of Macrophage Chemokine Expression by Lipopolysaccharide In Vitro and In Vivo
Kopydlowski, K. M., Salkowski, C. A., Cody, M. J., van Rooijen, N., Major, J. A., Hamilton, T. A., & Vogel, S. N. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.163.3.1537 · Cited by 311 · see citing works
Gabrusiewicz, K. R., Ellert‐Miklaszewska, A., Lipko, M. A., Sielska, M., Frankowska, M., & Kaminska, B. (2011) · PLoS ONE · doi:10.1371/journal.pone.0023902 · Cited by 256 · see citing works
Tanaka, R., Komine‐Kobayashi, M., Mochizuki, H., YAMADA, M., Furuya, T., Migita, M., Shimada, T., Mizuno, Y., & Urabe, T. (2003) · Neuroscience · doi:10.1016/s0306-4522(02)00954-5 · Cited by 237 · see citing works
Advanced Age Impairs Macrophage Polarization
Mahbub, S., Deburghgraeve, C. R., & Kovacs, E. J. (2012) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2011.0058 · Cited by 222 · see citing works
Stout, R. D., & Suttles, J. (2005) · Immunological Reviews · doi:10.1111/j.0105-2896.2005.00260.x · Cited by 220 · see citing works
Activation of Murine Macrophages
Mosser, D. M., & Zhang, X. (2008) · Current Protocols in Immunology · doi:10.1002/0471142735.im1402s83 · Cited by 211 · see citing works
Role of Interleukin-4 in Regulation of Age-related Inflammatory Changes in the Hippocampus
Nolan, Y. M., Maher, F. O., Martin, D. S. D., Clarke, R. M., Brady, M. T., Bolton, A. E., Mills, K. H. G., & Lynch, M. A. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m412170200 · Cited by 210 · see citing works
Self-citationBoehmer, E. D., Meehan, M. J., Cutro, B. T., & Kovacs, E. J. (2005) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2005.07.009 · Cited by 170 · see citing works
IFN-γ–dependent transcription of MHC class II IA is impaired in macrophages from aged mice
Herrero, C., Marqués, L., Lloberas, J., & Celada, A. (2001) · Journal of Clinical Investigation · doi:10.1172/jci11696 · Cited by 162 · see citing works
Girard, S., Brough, D., López‐Castejón, G., Giles, J. A., Rothwell, N. J., & Allan, S. M. (2013) · Glia · doi:10.1002/glia.22478 · Cited by 161 · see citing works
McMahon, E. J., Suzuki, K., & Matsushima, G. K. (2002) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(02)00205-9 · Cited by 161 · see citing works
Molecular basis of age-associated cytokine dysregulation in LPS-stimulated macrophages
Chelvarajan, R. L., Liu, Y., Popa, D., Getchell, M. L., Getchell, T. V., Stromberg, A. J., & Bondada, S. (2006) · Journal of Leukocyte Biology · doi:10.1189/jlb.0106024 · Cited by 151 · see citing works
Inflammatory processes in the aging mouse brain: Participation of dendritic cells and T-cells
Stichel, C. C., & Luebbert, H. (2007) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2006.07.022 · Cited by 151 · see citing works
Chelvarajan, R. L., Collins, S. M., Van Willigen, J. M., & Bondada, S. (2005) · Journal of Leukocyte Biology · doi:10.1189/jlb.0804449 · Cited by 141 · see citing works
Respiratory infection promotes T cell infiltration and amyloid-β deposition in APP/PS1 mice
McManus, R. M., Higgins, S. C., Mills, K. H. G., & Lynch, M. A. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.07.025 · Cited by 132 · see citing works
Self-citationDavila, D. R., Edwards, C. K., Arkins, S., Simon, J., & Kelley, K. W. (1990) · The FASEB Journal · doi:10.1096/fasebj.4.11.2165948 · Cited by 123 · see citing works
Minogue, A. M., Jones, R. S., Kelly, R. J., McDonald, C., Connor, T. J., & Lynch, M. A. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.12.026 · Cited by 108 · see citing works
Self-citationCD200 fusion protein decreases microglial activation in the hippocampus of aged rats
Cox, F., Carney, D. G., Miller, A., & Lynch, M. A. (2011) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2011.10.004 · Cited by 107 · see citing works
Self-citationLPS-induced release of IL-6 from glia modulates production of IL-1β in a JAK2-dependent manner
Minogue, A. M., Barrett, J. P., & Lynch, M. A. (2012) · Journal of Neuroinflammation · doi:10.1186/1742-2094-9-126 · Cited by 103 · see citing works
Self-citationDysregulated expression of miR‐146a contributes to age‐related dysfunction of macrophages
Jiang, M., Xiang, Y., Wang, D., Gao, J., Liu, D., Liu, Y., Liu, S., & Zheng, D. (2011) · Aging Cell · doi:10.1111/j.1474-9726.2011.00757.x · Cited by 102 · see citing works
Increased permeability of blood–brain barrier on the hippocampus of a murine model of senescence
Pelegrı́, C., Canudas, A. M., del Valle, J., Casadesús, G., Smith, M. A., Camins, A., Pallàs, M., & Vilaplana, J. (2007) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2007.07.002 · Cited by 93 · see citing works
Denieffe, S., Kelly, R. J., McDonald, C., Lyons, A., & Lynch, M. A. (2013) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2013.07.174 · Cited by 92 · see citing works
Self-citationBlau, C. W., Cowley, T. R., O'Sullivan, J., Grehan, B., Browne, T. C., Kelly, L., Birch, A., Murphy, N., Kelly, A. M., Kerskens, C. M., et al. (2012) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2011.09.035 · Cited by 92 · see citing works
Self-citationSebastián, C., Herrero, C., Serra, M., Lloberas, J., Blasco, M. A., & Celada, A. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0901131 · Cited by 90 · see citing works
Interleukin-4 mediates the neuroprotective effects of rosiglitazone in the aged brain
Loane, D. J., Deighan, B. F., Clarke, R. M., Griffin, R. J., Lynch, A. M., & Lynch, M. A. (2007) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.09.001 · Cited by 87 · see citing works
Self-citationAge and sex as factors modifying the function of the blood-cerebrospinal fluid barrier.
Pakulski, C., Drobnik, L., & Millo, B. (2001) · PubMed · Cited by 71 · see citing works
Age effects on macrophage function vary by tissue site, nature of stimulant, and exercise behavior
Kohut, M. L., Senchina, D. S., Madden, K. S., Martin, A., Felten, D. L., & Moynihan, J. A. (2004) · Experimental Gerontology · doi:10.1016/j.exger.2004.07.001 · Cited by 68 · see citing works
Rosiglitazone attenuates the age-related changes in astrocytosis and the deficit in LTP
Cowley, T. R., O’Sullivan, J. B., Blau, C. W., Deighan, B. F., Jones, R. S., Kerskens, C., Richardson, J. C., Virley, D. J., Upton, N., & Lynch, M. A. (2010) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2010.02.002 · Cited by 57 · see citing works
Self-citationSmallwood, H. S., López‐Ferrer, D., & Squier, T. C. (2011) · Biochemistry · doi:10.1021/bi2011866 · Cited by 56 · see citing works
Fallah, M. P., Chelvarajan, R. L., Garvy, B. A., & Bondada, S. (2011) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2011.05.003 · Cited by 48 · see citing works
Glial Activation in AβPP/PS1 Mice is Associated with Infiltration of IFNγ-Producing Cells
Kelly, R. J., Minogue, A. M., Lyons, A., Jones, R. S., Browne, T. C., Costello, D. A., Denieffe, S., O'Sullivan, C., Connor, T. J., & Lynch, M. A. (2013) · Journal of Alzheimer s Disease · doi:10.3233/jad-130539 · Cited by 48 · see citing works
Self-citationCcr2 Deficiency Impairs Microglial Accumulation and Accelerates Progression of Alzheimer's Disease
Khoury, J. B. E., Graham, M., Hickman, S. E., Geula, C., Means, T. K., & Luster, A. D. (2007) · Clinical Immunology · doi:10.1016/j.clim.2007.03.030 · Cited by 38 · see citing works
Lyons, A., Murphy, K. J., Clarke, R. M., & Lynch, M. A. (2011) · Journal of Neuroinflammation · doi:10.1186/1742-2094-8-27 · Cited by 34 · see citing works
Self-citationSimilar responses by macrophages from young and old mice infected with Mycobacterium tuberculosis
Rhoades, E. R., & Orme, I. M. (1998) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(98)00113-4 · Cited by 30 · see citing works
Defective pro-IL-1β responses in macrophages from aged mice
Ramirez, A., Rathinam, V. A. K., Fitzgerald, K. A., Golenbock, D. T., & Mathew, A. (2012) · Immunity & Ageing · doi:10.1186/1742-4933-9-27 · Cited by 23 · see citing works
Ingress of blood-borne macrophages across the blood-brain barrier in murine HIV-1 encephalitis
Liu, Y., Uberti, M., Dou, H., Banerjee, R., Grotepas, C. B., Stone, D. K., Rabinow, B. E., Gendelman, H. E., & Boska, M. D. (2008) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2008.06.009 · Cited by 19 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Aging, inflammation, stem cells, and bone healing
Gibon, E., Lu, L. Y., & Goodman, S. B. (2016) · Stem Cell Research & Therapy · doi:10.1186/s13287-016-0300-9 · Cited by 244 · see citing works
Immunoporosis: Role of Innate Immune Cells in Osteoporosis
Saxena, Y., Routh, S., & Mukhopadhaya, A. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.687037 · Cited by 230 · see citing works
Inflammatory microglia are glycolytic and iron retentive and typify the microglia in APP/PS1 mice
Holland, R., McIntosh, A. L., Finucane, O. M., Mela, V., Rubio‐Araiz, A., Timmons, G. A., McCarthy, S. A., Gun’ko, Y. K., & Lynch, M. A. (2017) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2017.10.017 · Cited by 217 · see citing works
Self-citationMcIntosh, A. L., Mela, V., Harty, C., Minogue, A. M., Costello, D. A., Kerskens, C., & Lynch, M. A. (2019) · Brain Pathology · doi:10.1111/bpa.12704 · Cited by 190 · see citing works
Self-citationBone regeneration in inflammation with aging and cell-based immunomodulatory therapy
Kushioka, J., Chow, S. K., Toya, M., Tsubosaka, M., Shen, H., Gao, Q., Li, X., Zhang, N., & Goodman, S. B. (2023) · Inflammation and Regeneration · doi:10.1186/s41232-023-00279-1 · Cited by 174 · see citing works
Hegdekar, N., Sarkar, C., Bustos, S., Ritzel, R. M., Hanscom, M., Ravishankar, P., Philkana, D., Wu, J., Loane, D. J., & Lipinski, M. M. (2023) · Autophagy · doi:10.1080/15548627.2023.2167689 · Cited by 158 · see citing works
Exploring Sex-Related Differences in Microglia May Be a Game-Changer in Precision Medicine
Lynch, M. A. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.868448 · Cited by 146 · see citing works
Self-citationInflammation, ageing, and bone regeneration
Gibon, E., Lu, L. Y., Nathan, K., & Goodman, S. B. (2017) · Journal of Orthopaedic Translation · doi:10.1016/j.jot.2017.04.002 · Cited by 144 · see citing works
Targeting innate immunity for neurodegenerative disorders of the central nervous system
Andreasson, K. I., Bachstetter, A. D., Colonna, M., Ginhoux, F., Holmes, C., Lamb, B., Landreth, G., Lee, D. C., Low, D., Lynch, M. A., et al. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13667 · Cited by 126 · see citing works
Self-citationLittlefield, A. M., Setti, S., Priester, C., & Kohman, R. (2015) · Journal of Neuroinflammation · doi:10.1186/s12974-015-0362-0 · Cited by 102 · see citing works
Controlled M1-to-M2 transition of aged macrophages by calcium phosphate coatings
Alhamdi, J. R., Peng, T., Al-Naggar, I. M., Hawley, K. L., Spiller, K. L., & Kuhn, L. T. (2019) · Biomaterials · doi:10.1016/j.biomaterials.2018.07.012 · Cited by 110 · see citing works
Mela, V., Mota, B. C., Milner, M. T., McGinley, A. M., Mills, K. H. G., Kelly, Á. M., & Lynch, M. A. (2020) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2020.01.012 · Cited by 98 · see citing works
Self-citationAlcohol, aging, and innate immunity
Boulé, L. A., & Kovacs, E. J. (2017) · Journal of Leukocyte Biology · doi:10.1189/jlb.4ru1016-450r · Cited by 92 · see citing works
Aging Affects Bone Marrow Macrophage Polarization: Relevance to Bone Healing
Gibon, E., Loi, F., Córdova, L. A., Pajarinen, J., Lin, T., Lu, L. Y., Nabeshima, A., Yao, Z., & Goodman, S. B. (2016) · Regenerative Engineering and Translational Medicine · doi:10.1007/s40883-016-0016-5 · Cited by 84 · see citing works
Macrophage depletion reduced brain injury following middle cerebral artery occlusion in mice
Ma, Y., Li, Y.-N., Jiang, L., Wang, L.-P., Jiang, Z., Wang, Y.-T., Zhang, Z., & Yang, G.-Y. (2016) · Journal of Neuroinflammation · doi:10.1186/s12974-016-0504-z · Cited by 77 · see citing works
Kühl, J.-S., Suarez, F., Gillett, G. T., Hemmati, P. G., Snowden, J. A., Stadler, M., Vuong, G. L., Aubourg, P., Köhler, W., & Arnold, R. (2017) · Brain · doi:10.1093/brain/awx016 · Cited by 78 · see citing works
Yarbro, J. R., Emmons, R. S., & Pence, B. D. (2020) · Immunometabolism · doi:10.20900/immunometab20200026 · Cited by 80 · 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
Jekabsone, A., Sīle, I., Cochis, A., Makrecka‐Kuka, M., Laucaitytė, G., Makarova, E., Rimondini, L., Bernotienė, R., Raudonė, L., Vedlugaite, E., et al. (2019) · Nutrients · doi:10.3390/nu11112829 · Cited by 66 · see citing works
The role of the immune system in driving neuroinflammation
Ní Chasaide, C., & Lynch, M. A. (2020) · Brain and Neuroscience Advances · doi:10.1177/2398212819901082 · Cited by 72 · see citing works
Self-citationMinogue, A. (2017) · Progress in Neuro-psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2017.02.008 · Cited by 56 · see citing works
3D Printed Pericardium Hydrogels To Promote Wound Healing in Vascular Applications
Bracaglia, L. G., Messina, M. J., Winston, S., Kuo, C., Lerman, M. J., & Fisher, J. P. (2017) · Biomacromolecules · doi:10.1021/acs.biomac.7b01165 · Cited by 61 · see citing works
Howe, A.-M., Burke, S., O’Reilly, M. E., McGillicuddy, F. C., & Costello, D. A. (2022) · Molecular Neurobiology · doi:10.1007/s12035-022-02756-z · Cited by 61 · see citing works
Self-citationCui, D., Lyu, J., Li, H., Lei, L., Bian, T., Li, L., & Yan, F. (2017) · Molecular Immunology · doi:10.1016/j.molimm.2017.08.012 · Cited by 54 · see citing works
Ji, H., Shen, G., Liu, H., Liu, Y., Qian, J., Wan, G., & Luo, E. (2024) · Bioactive Materials · doi:10.1016/j.bioactmat.2024.05.003 · Cited by 46 · see citing works
Dubayee, M. S. A., Alayed, H., Almansour, R., Alqaoud, N., Alnamlah, R., Obeid, D., Alshahrani, A. S., Zhra, M., Nasr, A., Al-Bawab, A., et al. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00537 · Cited by 36 · see citing works
Kumar, R., Sharma, A., Padwad, Y. S., & Sharma, R. (2020) · Biogerontology · doi:10.1007/s10522-020-09861-3 · Cited by 36 · see citing works
Zhao, Y., Suo, Y., Yang, Z., Hao, Y., Li, W., Su, Y., Shi, Y., Gao, Y., Song, L., Yin, X., et al. (2021) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2021.10.009 · Cited by 38 · see citing works
The crosstalk between macrophages and bone marrow mesenchymal stem cells in bone healing
Wang, Y., Zhao, C., Wang, R.-Y., Du, Q.-X., Liu, J., & Pan, J. (2022) · Stem Cell Research & Therapy · doi:10.1186/s13287-022-03199-y · Cited by 35 · see citing works
Donepezil Ameliorates Pulmonary Arterial Hypertension by Inhibiting M2-Macrophage Activation
Qiu, H., Zhang, Y., Li, Z., Jiang, P., Guo, S., He, Y., & Guo, Y. (2021) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2021.639541 · Cited by 34 · see citing works
Yuan, N., Zhang, W., Yang, W., Ji, W., & Li, J. (2024) · Journal of Orthopaedic Surgery and Research · doi:10.1186/s13018-024-04711-1 · Cited by 31 · see citing works
Costello, D. A., Keenan, K., McManus, R. M., Falvey, A., & Lynch, M. A. (2016) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.04.001 · Cited by 32 · see citing works
Self-citationYegla, B., & Foster, T. C. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00296 · Cited by 27 · see citing works
Role of Collagen Regulators in Cancer Treatment: A Comprehensive Review
Angre, T. D., Kumar, A., Singh, A. K., Thareja, S., & Kumar, P. (2022) · Anti-Cancer Agents in Medicinal Chemistry · doi:10.2174/1871520622666220501162351 · Cited by 27 · see citing works
The Potential Role and Therapeutic Relevance of Cellular Senescence in Skeletal Pathophysiology
Li, B., Lyu, P., Tang, J., Li, J., Ouchi, T., Fan, Y., Zhao, Z., & Li, L. (2024) · The Journals of Gerontology Series A · doi:10.1093/gerona/glae037 · Cited by 25 · see citing works
Aging and the immune response in diabetic peripheral neuropathy
Hagen, K. M., & Ousman, S. S. (2021) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2021.577574 · Cited by 25 · see citing works
Duong, L., Pixley, F. J., Nelson, D. J., & Jackaman, C. (2022) · Frontiers in Aging · doi:10.3389/fragi.2022.848925 · Cited by 23 · see citing works
Matatall, K. A., Wathan, T. K., Nguyen, M., Chen, H., McDonald, A., Qi, G., Belk, J. A., Florez, M. A., Le, D. T., Olarinde, T., et al. (2025) · Cell Stem Cell · doi:10.1016/j.stem.2025.06.006 · Cited by 23 · see citing works
Infiltrating macrophages contribute to age-related neuroinflammation in C57/BL6 mice
Wolfe, H. E., Minogue, A. M., Rooney, S., & Lynch, M. A. (2018) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2018.05.003 · Cited by 23 · see citing works
Self-citationDAMPs and influenza virus infection in ageing
Samy, R. P., & Lim, L. H. K. (2015) · Ageing Research Reviews · doi:10.1016/j.arr.2015.07.005 · Cited by 22 · see citing works
Han, X., Wang, F., Ma, Y., Lv, X., Zhang, K., Wang, Y., Yan, K., Mei, Y., & Wang, X. (2024) · Materials Today Bio · doi:10.1016/j.mtbio.2024.101036 · Cited by 21 · see citing works
How aging influences the gut-bone marrow axis and alters hematopoietic stem cell regulation
Wells, C., Robertson, T., Sheth, P. M., & Abraham, S. A. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e32831 · Cited by 21 · see citing works
Sharif, U., Mahmud, N. M., Kay, P., Yang, Y. C., Harding, S. P., Grierson, I., Kamalden, T. A., Jackson, M. J., & Paraoan, L. (2018) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.13944 · Cited by 21 · see citing works
Richert, I., BERCHARD, P., Abbes, L., Novikov, A., Chettab, K., Vandermoeten, A., Dumontet, C., Karanian, M., Kerzerho, J., Caroff, M., et al. (2023) · Cancers · doi:10.3390/cancers15184635 · Cited by 21 · see citing works
Yuan, B., Huang, S., Gong, S., Wang, F., Li, L., Su, T., Sheng, H., Shi, H. R., Ma, K., & Yang, Z. (2016) · Immunology Letters · doi:10.1016/j.imlet.2016.10.001 · Cited by 20 · see citing works
Drechsler, S., Lynch, M. A., Novella, S., Navarro, H. G., Hecimovic, S. K., Barini, E., Tucci, V., Castro, R. E., Vandenbroucke, R. E., Osuchowski, M. F., et al. (2016) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2016.07.005 · Cited by 19 · see citing works
Self-citationYe, X., Chen, J., Pan, J., Wu, Q., Wang, Y., Lu, M., Zhang, C., Zhang, Z., Ma, M., Zhu, J., et al. (2022) · Immunological Investigations · doi:10.1080/08820139.2022.2136525 · Cited by 17 · see citing works
Characterising lipoteichoic acid as an in vitro model of acute neuroinflammation
Howe, A.-M., Cosgrave, A., Murchú, M. Ó., Britchfield, C., Mulvagh, A., Fernández-Pérez, I., Dykstra, M., Jones, A. C., & Costello, D. A. (2020) · International Immunopharmacology · doi:10.1016/j.intimp.2020.106619 · Cited by 17 · see citing works
Self-citationDubayee, M. A., Alshahrani, A. S., Almalki, M. H., Hakami, A., Homoud, B., Alzneidi, N., Aldhalaan, J., Aljbli, G., Nasr, A., Farahat, A. I., et al. (2020) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2020.107758 · Cited by 15 · see citing works
Gonciarz, W., Brzeziński, M., Orłowska, W., Wawrzyniak, P., Lewandowski, A., Narayanan, V. H. B., & Chmiela, M. (2024) · Scientific Reports · doi:10.1038/s41598-024-55353-6 · Cited by 15 · see citing works
Microglial immune response is impaired against the neurotropic fungusLomentospora prolificans
Pellón, A., Ramirez‐Garcia, A., Guruceaga, X., Zabala, A., Buldain, I., Antoran, A., Anguíta, J., Rementerı́a, A., Matute, C., & Hernando, F. L. (2018) · Cellular Microbiology · doi:10.1111/cmi.12847 · Cited by 13 · see citing works
Effect of Aging on the Macrophage Response to Titanium Particles
Jämsen, E., Pajarinen, J., Lin, T., Lo, C., Nabeshima, A., Lu, L. Y., Nathan, K., Eklund, K. K., Yao, Z., & Goodman, S. B. (2019) · Journal of Orthopaedic Research® · doi:10.1002/jor.24461 · Cited by 13 · see citing works
Deng, Y., Yu, L., Lai, W., Xiao, S., & Zhang, W. (2024) · International Immunopharmacology · doi:10.1016/j.intimp.2024.112859 · Cited by 12 · see citing works
Valentine, M. S., Weigel, C., Gninzeko, F. J. K., Tho, C. K., Gräler, M. H., Reynolds, A., Spiegel, S., & Heise, R. L. (2022) · Experimental Gerontology · doi:10.1016/j.exger.2022.112074 · Cited by 9 · see citing works
Gonciarz, W., Chmiela, M., Kost, B., Piątczak, E., & Brzeziński, M. (2023) · Scientific Reports · doi:10.1038/s41598-023-34321-6 · Cited by 9 · see citing works
Molecular and Cellular Aspects of Macrophage Aging
Lloberas, J., Tur, J., Vico, T., & Celada, A. (2019) · Springer eBooks · doi:10.1007/978-3-319-99375-1_46 · Cited by 9 · see citing works
Antibiotic-induced gut microbiome remodeling reduces neuroinflammation in traumatic brain injury
Flinn, H., Marshall, A., Holcomb, M., Burke, M., Kara, G., Cruz-Pineda, L., Soriano, S., Treangen, T. J., & Villapol, S. (2026) · Communications Biology · doi:10.1038/s42003-026-09737-1 · Cited by 5 · see citing works
Regulation of Vascular Calcification by M1-Type Macrophage-Derived Semaphorin 4D
Park, H.-J., Kim, Y. S., Kim, M.-K., Kim, H. J., Bae, S., & Bae, M. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26115071 · Cited by 5 · see citing works
Stanojević, S., Ćuruvija, I., Blagojević, V., Petrović, R., Vujić, V., & Dimitrijević, M. (2016) · Experimental Gerontology · doi:10.1016/j.exger.2016.10.005 · Cited by 5 · see citing works
Ueshima, E., Sofue, K., Takaki, H., Hirata, Y., Kodama, H., Okada, T., Yamaguchi, M., Yamakado, K., & Murakami, T. (2023) · Journal of Vascular and Interventional Radiology · doi:10.1016/j.jvir.2023.07.025 · Cited by 4 · see citing works
Yosri, M., Mekky, A. E., Elaasser, M. M., Abdel‐Aziz, M. M., Youssef, F. S., Kamel, H. A., Al-Habibi, M. M., Helal, E. E.-H., & Amin, B. H. (2026) · Scientific Reports · doi:10.1038/s41598-025-32300-7 · Cited by 3 · see citing works
The Endocannabinoid System in Local and Systemic Inflammation
Kelly, M. E. M., Lehmann, C., & Zhou, J. (2017) · Colloquium Series on Integrated Systems Physiology From Molecule to Function · doi:10.4199/c00151ed1v01y201702isp074 · Cited by 3 · see citing works
Neurochemical Aspects of Alzheimer’s Type of Dementia
Farooqui, A. A. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-816347-4.00003-9 · Cited by 4 · see citing works
Vear, A., Chakraborty, A., Fahimi, F., Ferens, D. M., Widdop, R. E., Samuel, C. S., Gaspari, T. A., Endert, P. V., & Chai, S. Y. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1466692 · Cited by 2 · see citing works
Lu, R. J., Chen, S., Kim, M., Sampathkumar, N. K., Lee, E. H., Christensen, A., Wang, E., Lau, I. C. Y., Parihar, S., Ravikumar, C. K., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.06.11.659200 · Cited by 2 · see citing works
Ling, Z., Chen, C., Wang, S., Zhu, Y., Shen, X., Sun, K., Lu, H., & He, F. (2026) · Journal of Dentistry · doi:10.1016/j.jdent.2026.106516 · Cited by 1 · see citing works
Is Chronic Systemic Inflammation a Determinant Factor in Developing Parkinson’s Disease?
Ugalde‐Muñiz, P., Pérez‐Hernández, J., & Chavarría, A. (2016) · InTech eBooks · doi:10.5772/62955 · Cited by 1 · see citing works
The Effect of Diet and Natural Agents on Oral, Periodontal Health and Dentistry
Isola, G. (2020) · MDPI eBooks · doi:10.3390/books978-3-03943-512-8 · Cited by 1 · see citing works
Park, J.-E., Yun, J.-H., Lee, W., & Lee, J. S. (2024) · PLoS Pathogens · doi:10.1371/journal.ppat.1012474 · Cited by 1 · see citing works
Molecular and Cellular Aspects of Macrophage Aging
Lloberas, J., Tur, J., Vico, T., & Celada, A. (2017) · Springer eBooks · doi:10.1007/978-3-319-64597-1_46-1 · Cited by 1 · see citing works
Wu, Y., Xu, J., Sun, X.-H., Jiang, H., Zhou, H., Liu, Q., Cong, X., Wu, Y., & Lin, Z. (2024) · Research Square · doi:10.21203/rs.3.rs-4352075/v1 · Cited by 1 · see citing works
Modulating Aged Macrophages and Osteoprogenitors with a Calcium Phosphate Drug Delivery System
Alhamdi, J. R. (2018) · OpenCommons at University of Connecticut (University of Connecticut)
Biomimetic Therapeutics for Bone Regeneration: A Perspective on Antiaging Strategies
Miszuk, J. M., & Sun, H. (2023) · Macromolecular Bioscience · doi:10.1002/mabi.202300248
The Neuroimmune Landscape of the Lysosomal Storage Disorder Sanfilippo Syndrome
Badell‐Grau, R. A., & Schlachetzki, J. C. M. (2025) · BioEssays · doi:10.1002/bies.70083
Chen, K., You, X., Yu, W., Xu, Z., Wang, B., Ma, J., Zhao, X., Zhang, W., He, S., Gao, C., et al. (2025) · Biomaterials · doi:10.1016/j.biomaterials.2025.123865
Zhou, Q., Wang, K., Sun, X., Fu, J., Wang, L., Wang, Q., Ma, Y., & Guo, Y. (2026) · Immunity & Ageing · doi:10.1186/s12979-026-00586-4
- Authors
- Barrett, J. P., Costello, D. A., O’Sullivan, J., Cowley, T. R., & Lynch, M. A.
- Affiliations
- Trinity College Dublin (IE)
- Corresponding author
- Lynch, Marina A
- Venue
- Journal of Neuroinflammation
- Published
- 2015-04-09
- Volume
- 12
- Issue
- 1
- Pages
- 67-67
- ISSN
- 1742-2094 (ISSN-L)
- PMC
- PMC4397943
- OpenAlex
- W2078386495
- Cited by
- 76
- References
- 51
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 10 · 2023: 6 · 2022: 8 · 2021: 4 · 2020: 7 · 2019: 6 · 2018: 6 · 2017: 9 · 2016: 9 · 2015: 2
- FWCI
- 4.63
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Journal of Neuroinflammation (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Arrow@dit (Dublin Institute of Technology) (submittedVersion, cc-by-nc-sa)
- Funders
- Science Foundation Ireland (11/PI/1014)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- bone marrow-derived macrophages, aging, neuroinflammation, M1 macrophage activation, lipopolysaccharide, interferon-gamma, TNF-α, TLR4, IFN-gamma receptor, HMGB1, glial activation, macrophage infiltration
- MeSH terms
- Age Factors, Aging, Analysis of Variance, Animals, Animals, Newborn, Cells, Cultured, Enzyme-Linked Immunosorbent Assay, Gene Expression Regulation, Interferon-gamma, Lipopolysaccharides, Macrophages, Male, RNA, Messenger, Tumor Necrosis Factor-alpha, Cytokines, Rats, Wistar, Rats, Nitric Oxide Synthase Type II
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
