{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T11:12:45Z","timestamp":1788952365568,"version":"build-2803163510"},"reference-count":35,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,6,21]],"date-time":"2023-06-21T00:00:00Z","timestamp":1687305600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFD1800800"],"award-info":[{"award-number":["2021YFD1800800"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["32122086"],"award-info":[{"award-number":["32122086"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["32102749"],"award-info":[{"award-number":["32102749"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022M721277"],"award-info":[{"award-number":["2022M721277"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021CFA016"],"award-info":[{"award-number":["2021CFA016"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2662023PY005"],"award-info":[{"award-number":["2662023PY005"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2021YFD1800800"],"award-info":[{"award-number":["2021YFD1800800"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32122086"],"award-info":[{"award-number":["32122086"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32102749"],"award-info":[{"award-number":["32102749"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2022M721277"],"award-info":[{"award-number":["2022M721277"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2021CFA016"],"award-info":[{"award-number":["2021CFA016"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2662023PY005"],"award-info":[{"award-number":["2662023PY005"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2021YFD1800800"],"award-info":[{"award-number":["2021YFD1800800"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["32122086"],"award-info":[{"award-number":["32122086"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["32102749"],"award-info":[{"award-number":["32102749"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2022M721277"],"award-info":[{"award-number":["2022M721277"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2021CFA016"],"award-info":[{"award-number":["2021CFA016"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2662023PY005"],"award-info":[{"award-number":["2662023PY005"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Natural Science Foundation of Hubei Province","award":["2021YFD1800800"],"award-info":[{"award-number":["2021YFD1800800"]}]},{"name":"Natural Science Foundation of Hubei Province","award":["32122086"],"award-info":[{"award-number":["32122086"]}]},{"name":"Natural Science Foundation of Hubei Province","award":["32102749"],"award-info":[{"award-number":["32102749"]}]},{"name":"Natural Science Foundation of Hubei Province","award":["2022M721277"],"award-info":[{"award-number":["2022M721277"]}]},{"name":"Natural Science Foundation of Hubei Province","award":["2021CFA016"],"award-info":[{"award-number":["2021CFA016"]}]},{"name":"Natural Science Foundation of Hubei Province","award":["2662023PY005"],"award-info":[{"award-number":["2662023PY005"]}]},{"name":"Fundamental Research Funds for the Central Universities","award":["2021YFD1800800"],"award-info":[{"award-number":["2021YFD1800800"]}]},{"name":"Fundamental Research Funds for the Central Universities","award":["32122086"],"award-info":[{"award-number":["32122086"]}]},{"name":"Fundamental Research Funds for the Central Universities","award":["32102749"],"award-info":[{"award-number":["32102749"]}]},{"name":"Fundamental Research Funds for the Central Universities","award":["2022M721277"],"award-info":[{"award-number":["2022M721277"]}]},{"name":"Fundamental Research Funds for the Central Universities","award":["2021CFA016"],"award-info":[{"award-number":["2021CFA016"]}]},{"name":"Fundamental Research Funds for the Central Universities","award":["2662023PY005"],"award-info":[{"award-number":["2662023PY005"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Meningitis is a major clinical manifestation of Escherichia coli (E. coli) infection characterized by inflammation of the meninges and subarachnoid space. Many chemokines are secreted during meningitic E. coli infection, of which C-X-C motif chemokine 3 (CXCL3) is the most highly expressed. However, it is unclear how CXCL3 plays a role in meningitic E. coli infection. Therefore, this study used in vitro and in vivo assays to clarify these contributions and to identify novel therapeutic targets for central nervous system inflammation. We found a significantly upregulated expression of CXCL3 in human brain microvascular endothelial cells and U251 cells after meningitic E. coli infection, and the CXCL3 receptor, C-X-C motif chemokine receptor 2 (CXCR2), was expressed in microglia. Furthermore, CXCL3 induced M1 microglia by selectively activating mitogen-activated protein kinases signaling and significantly upregulating tumor necrosis factor-\u03b1 (TNF-\u03b1), interleukin (IL)-1\u03b2, IL-6, nitric oxide synthase 2 (NOS2), and cluster of differentiation 86 (CD86) expression levels, promoting an inflammatory response. Our findings clarify the role of CXCL3 in meningitic E. coli-induced neuroinflammation and demonstrate that CXCL3 may be a potential therapeutic target for future investigation and prevention of E. coli-induced neuroinflammation.<\/jats:p>","DOI":"10.3390\/ijms241310432","type":"journal-article","created":{"date-parts":[[2023,6,22]],"date-time":"2023-06-22T01:49:32Z","timestamp":1687398572000},"page":"10432","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["C-X-C Motif Chemokine 3 Promotes the Inflammatory Response of Microglia after Escherichia coli-Induced Meningitis"],"prefix":"10.3390","volume":"24","author":[{"given":"Xinyi","family":"Qu","sequence":"first","affiliation":[{"name":"National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China"},{"name":"Frontiers Science Center for Animal Breeding and Sustainable Production, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beibei","family":"Dou","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China"},{"name":"Frontiers Science Center for Animal Breeding and Sustainable Production, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruicheng","family":"Yang","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China"},{"name":"Frontiers Science Center for Animal Breeding and Sustainable Production, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Tan","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China"},{"name":"Frontiers Science Center for Animal Breeding and Sustainable Production, Wuhan 430070, China"},{"name":"Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture of the People\u2019s Republic of China, Wuhan 430070, China"},{"name":"International Research Center for Animal Disease, Ministry of Science and Technology of the People\u2019s Republic of China, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanchun","family":"Chen","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China"},{"name":"Frontiers Science Center for Animal Breeding and Sustainable Production, Wuhan 430070, China"},{"name":"Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture of the People\u2019s Republic of China, Wuhan 430070, China"},{"name":"International Research Center for Animal Disease, Ministry of Science and Technology of the People\u2019s Republic of China, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0191-1378","authenticated-orcid":false,"given":"Xiangru","family":"Wang","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China"},{"name":"Frontiers Science Center for Animal Breeding and Sustainable Production, Wuhan 430070, China"},{"name":"Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture of the People\u2019s Republic of China, Wuhan 430070, China"},{"name":"International Research Center for Animal Disease, Ministry of Science and Technology of the People\u2019s Republic of China, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1128\/ecosalplus.ESP-0015-2015","article-title":"Human meningitis-associated Escherichia coli","volume":"7","author":"Kim","year":"2016","journal-title":"EcoSal Plus"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.nbd.2003.12.016","article-title":"The blood-brain barrier: An overview: Structure, regulation, and clinical implications","volume":"16","author":"Ballabh","year":"2004","journal-title":"Neurobiol. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1023\/A:1011965307612","article-title":"Contractile proteins in pericytes at the blood-brain and blood-retinal barriers","volume":"30","author":"Bandopadhyay","year":"2001","journal-title":"J. Neurocytol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1038\/nrmicro1952","article-title":"Mechanisms of microbial traversal of the blood-brain barrier","volume":"6","author":"Kim","year":"2008","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.neuron.2008.01.003","article-title":"The blood-brain barrier in health and chronic neurodegenerative disorders","volume":"57","author":"Zlokovic","year":"2008","journal-title":"Neuron"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1038\/nrn3898","article-title":"Astrocyte barriers to neurotoxic inflammation","volume":"16","author":"Sofroniew","year":"2015","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3240","DOI":"10.1172\/JCI90606","article-title":"Microglia in Alzheimer\u2019s disease","volume":"127","author":"Sarlus","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.neuron.2012.12.023","article-title":"Microglia: New roles for the synaptic stripper","volume":"77","author":"Kettenmann","year":"2013","journal-title":"Neuron"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"856","DOI":"10.2533\/chimia.2016.856","article-title":"Chemokines: Chemistry, biochemistry and biological function","volume":"70","author":"Legler","year":"2016","journal-title":"Chimia"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/j.immuni.2012.05.008","article-title":"The chemokine superfamily revisited","volume":"36","author":"Zlotnik","year":"2012","journal-title":"Immunity"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1806","DOI":"10.1194\/jlr.M067207","article-title":"CXCL3 positively regulates adipogenic differentiation","volume":"57","author":"Kusuyama","year":"2016","journal-title":"J. Lipid Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1146\/annurev-immunol-032713-120145","article-title":"Chemokines and chemokine receptors: Positioning cells for host defense and immunity","volume":"32","author":"Griffith","year":"2014","journal-title":"Annu. Rev. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/978-3-030-62658-7_2","article-title":"CXCL3 signaling in the tumor microenvironment","volume":"1302","author":"Reyes","year":"2021","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.ijbiomac.2017.09.032","article-title":"Molecular cloning and biophysical characterization of CXCL3 chemokine","volume":"107","author":"Gulati","year":"2017","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5269","DOI":"10.4049\/jimmunol.165.9.5269","article-title":"The CXC chemokine receptor 2, CXCR2, is the putative receptor for ELR+ CXC chemokine-induced angiogenic activity","volume":"165","author":"Addison","year":"2000","journal-title":"J. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2731","DOI":"10.4049\/jimmunol.1203421","article-title":"Differential roles of CXCL2 and CXCL3 and their receptors in regulating normal and asthmatic airway smooth muscle cell migration","volume":"191","author":"Chang","year":"2013","journal-title":"J. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"38903","DOI":"10.1038\/srep38903","article-title":"Differential transcription profiles of long non-coding RNAs in primary human brain microvascular endothelial cells in response to meningitic Escherichia coli","volume":"6","author":"Yang","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.2217\/epi-2019-0342","article-title":"Holistic insights into meningitic Escherichia coli infection of astrocytes based on whole transcriptome profiling","volume":"12","author":"Yang","year":"2020","journal-title":"Epigenomics"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Yang, R., Wang, J., Wang, F., Zhang, H., Tan, C., Chen, H., and Wang, X. (2023). Blood-brain barrier integrity damage in bacterial meningitis: The underlying link, mechanisms, and therapeutic targets. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032852"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/s00401-015-1531-z","article-title":"Host\u2013pathogen interactions in bacterial meningitis","volume":"131","author":"Doran","year":"2016","journal-title":"Acta Neuropathol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Korbecki, J., Kojder, K., Kapczuk, P., Kupnicka, P., Gawro\u0144ska-Szklarz, B., Gutowska, I., Chlubek, D., and Baranowska-Bosiacka, I. (2021). The effect of hypoxia on the expression of CXC chemokines and CXC chemokine receptors-a review of literature. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22020843"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Korbecki, J., Kupnicka, P., Chlubek, M., Gor\u0105cy, J., Gutowska, I., and Baranowska-Bosiacka, I. (2022). CXCR2 receptor: Regulation of expression, signal transduction, and involvement in cancer. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23042168"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Boissi\u00e8re-Michot, F., Jacot, W., Massol, O., Mollevi, C., and Lazennec, G. (2021). CXCR2 levels correlate with immune infiltration and a better prognosis of triple-negative breast cancers. Cancers, 13.","DOI":"10.3390\/cancers13102328"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.cyto.2017.02.007","article-title":"Duffy antigen receptor for chemokines (DARC) expressing in cancer cells inhibits tumor progression by suppressing CXCR2 signaling in human pancreatic ductal adenocarcinoma","volume":"95","author":"Maeda","year":"2017","journal-title":"Cytokine"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.molimm.2018.01.011","article-title":"Anti-inflammatory effects of anisalcohol on lipopolysaccharide-stimulated BV2 microglia via selective modulation of microglia polarization and down-regulation of NF-kappaB p65 and JNK activation","volume":"95","author":"Xiang","year":"2018","journal-title":"Mol. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nrn2038","article-title":"Microglia-mediated neurotoxicity: Uncovering the molecular mechanisms","volume":"8","author":"Block","year":"2007","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1186\/1742-2094-8-174","article-title":"Temporal pattern of expression and colocalization of microglia\/macrophage phenotype markers following brain ischemic injury in mice","volume":"8","author":"Perego","year":"2011","journal-title":"J. Neuroinflamm."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"12106","DOI":"10.1038\/s41598-019-48609-z","article-title":"S1P2 contributes to microglial activation and M1 polarization following cerebral ischemia through ERK1\/2 and JNK","volume":"9","author":"Sapkota","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Kanazawa, M., Ninomiya, I., Hatakeyama, M., Takahashi, T., and Shimohata, T. (2017). Microglia and monocytes\/macrophages polarization reveal novel therapeutic mechanism against stroke. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18102135"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/1742-2094-11-23","article-title":"Macrophages migrate in an activation-dependent manner to chemokines involved in neuroinflammation","volume":"11","author":"Vogel","year":"2014","journal-title":"J. Neuroinflamm."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"525","DOI":"10.3389\/fncel.2019.00525","article-title":"Relationship of inflammatory cytokines from M1-type microglia\/macrophages at the injured site and lumbar enlargement with neuropathic pain after spinal cord injury in the CCL21 knockout (plt) mouse","volume":"13","author":"Honjoh","year":"2019","journal-title":"Front. Cell. Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1097\/BOR.0000000000000835","article-title":"Contribution of monocytes and macrophages to the pathogenesis of systemic sclerosis: Recent insights and therapeutic implications","volume":"33","author":"Lescoat","year":"2021","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1007\/s11255-018-1818-9","article-title":"Chemokine CXCL3 mediates prostate cancer cells proliferation, migration and gene expression changes in an autocrine\/paracrine fashion","volume":"50","author":"Xin","year":"2018","journal-title":"Int. Urol. Nephrol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1186\/s12974-022-02514-x","article-title":"SARS-CoV-2 productively infects human brain microvascular endothelial cells","volume":"19","author":"Yang","year":"2022","journal-title":"J. Neuroinflamm."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.abb.2019.05.011","article-title":"STAT1 drives M1 microglia activation and neuroinflammation under hypoxia","volume":"669","author":"Butturini","year":"2019","journal-title":"Arch. Biochem. Biophys."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/13\/10432\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:57:53Z","timestamp":1760126273000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/13\/10432"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,21]]},"references-count":35,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["ijms241310432"],"URL":"https:\/\/doi.org\/10.3390\/ijms241310432","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,21]]}}}