{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:51:44Z","timestamp":1772160704502,"version":"3.50.1"},"reference-count":52,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Astrocytes, the most abundant glial cells in the CNS, play a crucial role in supporting neurons and respond to injury or disease through astrogliosis, a process marked by cellular hypertrophy and increased glial fibrillary acidic protein (GFAP) expression. Interleukin\u201033 (IL\u201033) was originally identified as an alarmin and is known to be produced by astrocytes and oligodendrocytes in the CNS. Recently, we reported its role in regulating oligodendrocyte differentiation. However, its role in astrocytes remains less defined. In a demyelinating mouse model induced by gliotoxin cuprizone (CPZ), IL\u201033 was previously shown to be reduced in oligodendrocytes within the corpus callosum. In this study, we found that lipopolysaccharide (LPS) stimulation enhanced nuclear IL\u201033 expression and GFAP production in cortical astrocytes. Using lentiviral\u2010mediated IL\u201033 knockdown (IL33KD) and overexpression (IL33oe), we demonstrated that IL\u201033 positively regulates GFAP expression. Interestingly, we observed an increase in nuclear IL\u201033\u2010expressing GFAP\n                    <jats:sup>+<\/jats:sup>\n                    cortical astrocytes in CPZ\u2010treated mice. In contrast, CPZ\u2010induced GFAP upregulation in cortical astrocytes was abolished in IL\u201033 knockout (\n                    <jats:italic>il33<\/jats:italic>\n                    <jats:sup>KO<\/jats:sup>\n                    ) mice. Furthermore, chronic CPZ feeding in\n                    <jats:italic>il33<\/jats:italic>\n                    <jats:sup>KO<\/jats:sup>\n                    mice led to increased microgliosis and neuronal damage within the frontal cortex, as well as abnormal anxiety\u2010like behaviors. Collectively, these results indicate that elevated nuclear IL\u201033 in astrocytes under inflammatory conditions is critical for GFAP upregulation and astrogliosis. Loss of IL\u201033 disrupts astrocyte neuroprotective functions and glial reactivity in the frontal cortex, contributing to behavioral abnormalities under a demyelinating insult.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70310-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.70310","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T09:35:39Z","timestamp":1764927339000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Astrocytic Interleukin\u201033 Deficiency Reduces Glial Fibrillary Acidic Protein Expression and Exacerbates Microglial Activation and Neuronal Damage in a Chemically Induced Inflamed Frontal Cortex"],"prefix":"10.1111","volume":"169","author":[{"given":"Yu\u2010Chen","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Life Sciences College of Bioscience and Biotechnology, National Cheng Kung University  Tainan Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9325-8734","authenticated-orcid":false,"given":"Wei\u2010Yu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology and Institute of Basic Medical Sciences College of Medicine, National Cheng Kung University  Tainan 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