{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T01:53:37Z","timestamp":1783216417490,"version":"3.54.6"},"reference-count":78,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,3,26]],"date-time":"2020-03-26T00:00:00Z","timestamp":1585180800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012854","name":"Children's Hospital Research Institute of Manitoba","doi-asserted-by":"publisher","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}],"id":[{"id":"10.13039\/100012854","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Autophagy is a key cellular process that involves constituent degradation and recycling during cellular development and homeostasis. Autophagy also plays key roles in antimicrobial host defense and numerous pathogenic organisms have developed strategies to take advantage of and\/or modulate cellular autophagy. Several pharmacologic compounds, such as BafilomycinA1, an autophagy inducer, and Rapamycin, an autophagy inhibitor, have been used to modulate autophagy, and their effects upon notable autophagy markers, such as LC3 protein lipidation and Sequestosome-1\/p62 alterations are well defined. We sought to understand whether such autophagy modulators have a more global effect upon host cells and used a recently developed aptamer-based proteomic platform (SOMAscan\u00ae) to examine 1305 U-251 astrocytic cell proteins after the cells were treated with each compound. These analyses, and complementary cytokine array analyses of culture supernatants after drug treatment, revealed substantial perturbations in the U-251 astrocyte cellular proteome. Several proteins, including cathepsins, which have a role in autophagy, were differentially dysregulated by the two drugs as might be expected. Many proteins, not previously known to be involved in autophagy, were significantly dysregulated by the compounds, and several, including lactadherin and granulins, were up-regulated by both drugs. These data indicate that these two compounds, routinely used to help dissect cellular autophagy, have much more profound effects upon cellular proteins.<\/jats:p>","DOI":"10.3390\/cells9040805","type":"journal-article","created":{"date-parts":[[2020,4,1]],"date-time":"2020-04-01T05:52:30Z","timestamp":1585720350000},"page":"805","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Autophagy Modulators Profoundly Alter the Astrocyte Cellular Proteome"],"prefix":"10.3390","volume":"9","author":[{"given":"Affan Ali","family":"Sher","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology &amp; Infectious Diseases, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ang","family":"Gao","sequence":"additional","affiliation":[{"name":"Manitoba Centre for Proteomics &amp; Systems Biology, University of Manitoba, Winnipeg, MB R3E 3P4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin M.","family":"Coombs","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology &amp; Infectious Diseases, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"},{"name":"Manitoba Centre for Proteomics &amp; Systems Biology, University of Manitoba, Winnipeg, MB R3E 3P4, Canada"},{"name":"Children\u2019s Hospital Research Institute of Manitoba, Winnipeg, MB R3E 3P4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1146\/annurev-genet-102808-114910","article-title":"Regulation mechanisms and signaling pathways of autophagy","volume":"43","author":"He","year":"2009","journal-title":"Annu. Rev. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1083\/jcb.201402054","article-title":"Organellophagy: Eliminating cellular building blocks via selective autophagy","volume":"205","author":"Okamoto","year":"2014","journal-title":"J. Cell Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/15548627.2015.1100356","article-title":"Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)","volume":"12","author":"Klionsky","year":"2016","journal-title":"Autophagy"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.1242\/jcs.031773","article-title":"Mammalian macroautophagy at a glance","volume":"122","author":"Ravikumar","year":"2009","journal-title":"J. Cell Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1007\/s00018-011-0865-5","article-title":"Microautophagy: Lesser-known self-eating","volume":"69","author":"Li","year":"2011","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.cmet.2014.06.009","article-title":"Deficient chaperone-mediated autophagy in liver leads to metabolic dysregulation","volume":"20","author":"Schneider","year":"2014","journal-title":"Cell Metab."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1242\/jcs.073874","article-title":"Chaperone-mediated autophagy at a glance","volume":"124","author":"Kaushik","year":"2011","journal-title":"J. Cell Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"5747","DOI":"10.1128\/MCB.02070-07","article-title":"The chaperone-mediated autophagy receptor organizes in dynamic protein complexes at the lysosomal membrane","volume":"28","author":"Bandyopadhyay","year":"2008","journal-title":"Mol. Cell Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1093\/neuonc\/noy034","article-title":"mTOR inhibition in glioblastoma: Requiem for a dream?","volume":"20","author":"Babak","year":"2018","journal-title":"Neuro-Oncology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2018\/9230479","article-title":"Targeting mTOR in glioblastoma: Rationale and preclinical\/clinical evidence","volume":"2018","author":"Mecca","year":"2018","journal-title":"Dis. Mark."},{"key":"ref_11","first-page":"2477","article-title":"Effect and molecular mechanism of mTOR inhibitor rapamycin on temozolomide-induced autophagic death of U251 glioma cells","volume":"15","author":"Li","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"5","DOI":"10.2217\/cns.13.52","article-title":"How efficient are autophagy inhibitors as treatment for glioblastoma?","volume":"3","author":"Wojton","year":"2014","journal-title":"CNS Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Cloughesy, T.F., Yoshimoto, K., Nghiemphu, P., Brown, K., Dang, J., Zhu, S., Hsueh, T., Chen, Y., Wang, W., and Youngkin, D. (2008). Antitumor activity of rapamycin in a phase I trial for patients with recurrent PTEN-deficient glioblastoma. PLoS Med., 5.","DOI":"10.1371\/journal.pmed.0050008"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.4103\/1673-5374.257524","article-title":"The local mammalian target of rapamycin (mTOR) modulation: A promising strategy to counteract neurodegeneration","volume":"14","author":"Dolcetta","year":"2019","journal-title":"Neural Regen. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1111\/j.1471-4159.2010.06838.x","article-title":"Low-dose bafilomycin attenuates neuronal cell death associated with autophagy-lysosome pathway dysfunction","volume":"114","author":"Pivtoraiko","year":"2010","journal-title":"J. Neurochem."},{"key":"ref_16","first-page":"e15004","article-title":"Aptamer-based multiplexed proteomic technology for biomarker discovery","volume":"5","author":"Gold","year":"2010","journal-title":"Nat. Proced."},{"key":"ref_17","unstructured":"(2017). SOMAScan Proteomic Assay, SomaLogic. SSM-002."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s12943-019-0944-z","article-title":"The relationship between autophagy and the immune system and its applications for tumor immunotherapy","volume":"18","author":"Jiang","year":"2019","journal-title":"Mol. Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Jang, Y.J., Kim, J.H., and Byun, S. (2019). Modulation of autophagy for controlling immunity. Cells, 8.","DOI":"10.3390\/cells8020138"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1111\/j.1365-2249.2011.04544.x","article-title":"Cell death pathways and autophagy in the central nervous system and its involvement in neurodegeneration, immunity and central nervous system infection: To die or not to die\u2014that is the question","volume":"168","author":"Rosello","year":"2012","journal-title":"Clin. Exp. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1111\/j.1460-9568.2010.07500.x","article-title":"Autophagy, inflammation and neurodegenerative disease","volume":"33","author":"Alirezaei","year":"2010","journal-title":"Eur. J. Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.neuroscience.2016.01.035","article-title":"The role of autophagy in modulation of neuroinflammation in microglia","volume":"319","author":"Su","year":"2016","journal-title":"Neuroscience"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1800309","DOI":"10.1002\/pmic.201800309","article-title":"Vero cell proteomic changes induced by Zika virus infection","volume":"19","author":"Glover","year":"2019","journal-title":"Proteomics"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"596","DOI":"10.3389\/fmicb.2019.00596","article-title":"Zika virus infection disrupts astrocytic proteins involved in synapse control and axon guidance","volume":"10","author":"Sher","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"10888","DOI":"10.1128\/JVI.00431-10","article-title":"Quantitative proteomic analyses of influenza virus-infected cultured human lung cells","volume":"84","author":"Coombs","year":"2010","journal-title":"J. Virol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1038\/ncb0707-741","article-title":"Autophagy: A new regulator of development","volume":"9","year":"2007","journal-title":"Nat. Cell Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.devcel.2008.08.012","article-title":"The role of autophagy in mammalian development: Cell makeover rather than cell death","volume":"15","author":"Cecconi","year":"2008","journal-title":"Dev. Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/j.devcel.2018.02.014","article-title":"Autophagy inhibition mediates apoptosis sensitization in cancer therapy by relieving FOXO3a turnover","volume":"44","author":"Fitzwalter","year":"2018","journal-title":"Dev. Cell"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1016\/j.febslet.2010.01.009","article-title":"Autophagy in cellular growth control","volume":"584","author":"Wang","year":"2010","journal-title":"FEBS Lett."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1080\/15548627.2015.1066957","article-title":"Bafilomycin A1 disrupts autophagic flux by inhibiting both V-ATPase-dependent acidification and Ca-P60A\/SERCA-dependent autophagosome-lysosome fusion","volume":"11","author":"Mauvezin","year":"2015","journal-title":"Autophagy"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.3892\/etm.2017.4618","article-title":"Role of mammalian target of rapamycin signaling in autophagy and the neurodegenerative process using a senescence accelerated mouse-prone 8 model","volume":"14","author":"Wang","year":"2017","journal-title":"Exp. Ther. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5696","DOI":"10.1523\/JNEUROSCI.20-15-05696.2000","article-title":"Clinical mutations in the L1 neural cell adhesion molecule affect cell-surface expression","volume":"20","author":"Moulding","year":"2000","journal-title":"J. Neurosci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3716","DOI":"10.1038\/s41598-019-39884-x","article-title":"L1cam-mediated developmental processes of the nervous system are differentially regulated by proteolytic processing","volume":"9","author":"Linneberg","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1523\/JNEUROSCI.4178-07.2008","article-title":"A transcriptome database for astrocytes, neurons, and oligodendrocytes: A new resource for understanding brain development and function","volume":"28","author":"Cahoy","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1002\/jcp.26918","article-title":"MFG-E8 reverses microglial-induced neurotoxic astrocyte (A1) via NF-kappa B and PI3K-Akt pathways","volume":"234","author":"Xu","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"569","DOI":"10.3389\/fnins.2019.00569","article-title":"Neurogenesis in neurodegenerative diseases: Role of MFG-E8","volume":"13","author":"Cheyuo","year":"2019","journal-title":"Front. Mol. Neurosci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s40478-019-0669-7","article-title":"EphB2-dependent signaling promotes neuronal excitotoxicity and inflammation in the acute phase of ischemic stroke","volume":"7","author":"Ernst","year":"2019","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"7789","DOI":"10.1523\/JNEUROSCI.23-21-07789.2003","article-title":"Ephrin-B2 and EphB2 Regulation of astrocyte-meningeal fibroblast interactions in response to spinal cord lesions in adult rats","volume":"23","author":"Bundesen","year":"2003","journal-title":"J. Neurosci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1111\/j.1471-4159.2004.02984.x","article-title":"Astrocyte activation by fibroblast growth factor-1 and motor neuron apoptosis: Implications for amyotrophic lateral sclerosis","volume":"93","author":"Cassina","year":"2005","journal-title":"J. Neurochem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.cell.2004.12.020","article-title":"Thrombospondins are astrocyte-secreted proteins that promote CNS synaptogenesis","volume":"120","author":"Christopherson","year":"2005","journal-title":"Cell"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"59","DOI":"10.2350\/14-06-1516-CR.1","article-title":"Complex brain malformations associated with chromosome 6q27 gain that includes THBS2, which encodes thrombospondin 2, an astrocyte-derived protein of the extracellular matrix","volume":"18","author":"Burnside","year":"2015","journal-title":"Pediatr. Dev. Pathol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1194\/jlr.M014118","article-title":"PCSK9 reduces the protein levels of the LDL receptor in mouse brain during development and after ischemic stroke","volume":"52","author":"Rousselet","year":"2011","journal-title":"J. Lipid Res."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Picard, C., Poirier, A., Belanger, S., Labonte, A., Auld, D., Poirier, J., Breitner, J.C.S., Poirier, J., Etienne, P., and Villeneuve, S. (2019). Proprotein convertase subtilisin\/kexin type 9 (PCSK9) in Alzheimer\u2019s disease: A genetic and proteomic multi-cohort study. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0220254"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"389","DOI":"10.4161\/cbt.19237","article-title":"Granulocyte-colony stimulating factor promotes proliferation, migration and invasion in glioma cells","volume":"13","author":"Wang","year":"2012","journal-title":"Cancer Biol. Ther."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1948","DOI":"10.1210\/endo.131.4.1396338","article-title":"Involvement of protein-kinase-C in the mitogenic effect of insulin-like growth factor-I on rat astrocytes","volume":"131","author":"Tranque","year":"1992","journal-title":"Endocrinology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"5225","DOI":"10.1038\/onc.2013.524","article-title":"Protein kinase C and cancer: What we know and what we do not","volume":"33","author":"Garg","year":"2013","journal-title":"Oncogene"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Scholze, A.R., Foo, L.C., Mulinyawe, S., and Barres, B.A. (2014). BMP signaling in astrocytes downregulates EGFR to modulate survival and maturation. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0110668"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1186\/s40478-019-0727-1","article-title":"Tenascin-C expression contributes to pediatric brainstem glioma tumor phenotype and represents a novel biomarker of disease","volume":"7","author":"Qi","year":"2019","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"7084","DOI":"10.1093\/nar\/gku373","article-title":"Protein kinase C controls activation of the DNA integrity checkpoint","volume":"42","author":"Quilis","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/j.expneurol.2004.12.022","article-title":"Astrocyte growth effects of vascular endothelial growth factor (VEGF) application to perinatal neocortical explants: Receptor mediation and signal transduction pathways","volume":"192","author":"Mani","year":"2005","journal-title":"Exp. Neurol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2454","DOI":"10.1172\/JCI60842","article-title":"Astrocyte-derived VEGF-A drives blood-brain barrier disruption in CNS inflammatory disease","volume":"122","author":"Argaw","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1186\/1742-2094-9-262","article-title":"Platelet-derived growth factor (PDGF)-BB-mediated induction of monocyte chemoattractant protein 1 in human astrocytes: Implications for HIV-associated neuroinflammation","volume":"9","author":"Yao","year":"2012","journal-title":"J. Neuroinflammation"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Hindinger, C., Bergmann, C., Hinton, D.R., Phares, T.W., Parra, G.I., Hussain, S., Savarin, C., Atkinson, R.D., and Stohlman, S.A. (2012). IFN-\u03b3 signaling to astrocytes protects from autoimmune mediated neurological disability. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0042088"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.molmet.2017.01.010","article-title":"Astrocyte IKK\u03b2\/NF-\u03baB signaling is required for diet-induced obesity and hypothalamic inflammation","volume":"6","author":"Douglass","year":"2017","journal-title":"Mol. Metab."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1016\/j.cmet.2017.04.002","article-title":"Astrocytic process plasticity and IKK\u03b2\/NF-\u03baB in central control of blood glucose, blood pressure, and body weight","volume":"25","author":"Zhang","year":"2017","journal-title":"Cell Metab."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1007\/s11481-013-9479-z","article-title":"The roles of PDGF in development and during neurogenesis in the normal and diseased nervous system","volume":"9","author":"Funa","year":"2013","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"4251","DOI":"10.4049\/jimmunol.1303321","article-title":"Silencing IFN-\u03b3 binding\/signaling in astrocytes versus microglia leads to opposite effects on central nervous system autoimmunity","volume":"194","author":"Ding","year":"2015","journal-title":"J. Immunol."},{"key":"ref_58","first-page":"259","article-title":"Regulation of immune cell entry into the central nervous system","volume":"43","author":"Engelhardt","year":"2006","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1177\/019262338701500307","article-title":"Immune responses in the central nervous system","volume":"15","author":"Griffin","year":"1987","journal-title":"Toxicol. Pathol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1038\/ni.3656","article-title":"Infectious immunity in the central nervous system and brain function","volume":"18","author":"Klein","year":"2017","journal-title":"Nat. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.yfrne.2011.12.002","article-title":"Cytokines and brain excitability","volume":"33","author":"Galic","year":"2011","journal-title":"Front. Neuroendocr."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"4369","DOI":"10.1128\/JVI.79.7.4369-4381.2005","article-title":"Viral induction of central nervous system innate immune responses","volume":"79","author":"Rempel","year":"2005","journal-title":"J. Virol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1172\/JCI58648","article-title":"The adaptive immune system in diseases of the central nervous system","volume":"122","author":"Wraith","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"136","DOI":"10.3389\/fnsyn.2010.00136","article-title":"Novel roles for immune molecules in neural development: Implications for neurodevelopmental disorders","volume":"2","author":"Garay","year":"2010","journal-title":"Front. Synaptic Neurosci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1016\/j.bbamcr.2011.01.034","article-title":"The pro- and anti-inflammatory properties of the cytokine interleukin-6","volume":"1813","author":"Scheller","year":"2011","journal-title":"Biochim. Biophys. Acta (BBA) Mol. Cell Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2066","DOI":"10.3389\/fimmu.2019.02066","article-title":"Innate immunity in the central nervous system: A missing piece of the autoimmune encephalitis puzzle?","volume":"10","author":"Wesselingh","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1016\/j.smim.2013.10.005","article-title":"Interleukin-1\u03b1","volume":"25","author":"Rider","year":"2013","journal-title":"Semin. Immunol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1016\/j.immuni.2017.06.006","article-title":"Reactive astrocytes: Production, function, and therapeutic potential","volume":"46","author":"Liddelow","year":"2017","journal-title":"Immunity"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s12974-015-0474-6","article-title":"CXCL5 signaling is a shared pathway of neuroinflammation and blood-brain barrier injury contributing to white matter injury in the immature brain","volume":"13","author":"Wang","year":"2016","journal-title":"J. Neuroinflammation"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1089\/jir.2014.0135","article-title":"Transcriptional regulation of CXCL5 in HIV-1-infected macrophages and its functional consequences on CNS pathology","volume":"35","author":"Guha","year":"2015","journal-title":"J. Interferon Cytokine Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1038\/nri2565","article-title":"Regulation of innate immune responses in the brain","volume":"9","author":"Rivest","year":"2009","journal-title":"Nat. Rev. Immunol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"544","DOI":"10.3389\/fimmu.2016.00683","article-title":"The skin\u2013brain connection hypothesis, bringing together CCL27-mediated T-cell activation in the skin and neural cell damage in the adult brain","volume":"7","author":"Blatt","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"531","DOI":"10.3389\/fimmu.2017.00531","article-title":"Elevated levels of proinflammatory cytokines in cerebrospinal fluid of multiple sclerosis patients","volume":"8","author":"Khaibullin","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1016\/j.immuni.2019.03.012","article-title":"Interleukin-1 and related cytokines in the regulation of inflammation and immunity","volume":"50","author":"Mantovani","year":"2019","journal-title":"Immunity"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Olmos, G., and Llado, J. (2014). Tumor necrosis factor alpha: A link between neuroinflammation and excitotoxicity. Mediat. Inflamm., 2014.","DOI":"10.1155\/2014\/861231"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1186\/s12974-015-0345-1","article-title":"TNF-dependent regulation and activation of innate immune cells are essential for host protection against cerebral tuberculosis","volume":"12","author":"Francisco","year":"2015","journal-title":"J. Neuroinflammation"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1016\/j.yexmp.2015.07.010","article-title":"IL-9 signaling affects central nervous system resident cells during inflammatory stimuli","volume":"99","author":"Ding","year":"2015","journal-title":"Exp. Mol. Pathol."},{"key":"ref_78","first-page":"45","article-title":"Pericytes secrete pro-regenerative molecules in response to platelet-derived growth factor-BB","volume":"38","author":"Gaceb","year":"2017","journal-title":"Br. J. Pharmacol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/4\/805\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:12:01Z","timestamp":1760173921000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/4\/805"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,26]]},"references-count":78,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2020,4]]}},"alternative-id":["cells9040805"],"URL":"https:\/\/doi.org\/10.3390\/cells9040805","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,26]]}}}