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Life stresses may up\u2010regulate inflammatory processes and promote depression. Although cytokines are central to stress\u2010related immune responses, their contribution to stress\u2010induced depression remains unclear. Here, we used unpredictable chronic mild stress (UCMS) to induce depression\u2010like behaviors in mice, as assessed through a suite of behavioral tests. C\u2010X\u2010C motif chemokine ligand 1 (CXCL1)\u2010related molecular networks responsible for depression\u2010like behaviors were assessed through intrahippocampal microinjection of lenti\u2010CXCL1, the antidepressant fluoxetine, the C\u2010X\u2010C motif chemokine receptor 2 (CXCR2) inhibitor SB265610, and the glycogen synthase kinase\u20103\u03b2 (GSK3\u03b2) inhibitor AR\u2010A014418. Modulation of apoptosis\u2010related pathways and neuronal plasticity were assessed\n                    <jats:italic>via<\/jats:italic>\n                    quantification of cleaved caspase\u20103, B\u2010cell lymphoma 2\u2010associated X protein, cAMP response element\u2010binding protein (CREB), and brain\u2010derived neurotrophic factor (BDNF) protein expression. CXCL1\/CXCL2 expression was correlated with depression\u2010like behaviors in response to chronic stress or antidepressant treatment in the UCMS depression model. Intrahippocampal microinjection of lenti\u2010CXCL1 increased depression\u2010like behaviors, activated GSK3\u03b2, increased apoptosis pathways, suppressed CREB activation, and decreased BDNF. Administration of the selective GSK3\u03b2 inhibitor AR\u2010A014418 abolished the effects of lenti\u2010CXCL1, and the CXCR2 inhibitor SB265610 prevented chronic stress\u2010induced depression\u2010like behaviors, inhibited GSK3\u03b2 activity, blocked apoptosis pathways, and restored BDNF expression. The CXCL1\/CXCR2 axis appears to play a critical role in stress\u2010induced depression, and CXCR2 is a potential novel therapeutic target for patients with depression.\u2014Chai, H.\u2010H., Fu, X.\u2010C., Ma, L., Sun, H.\u2010T., Chen, G.\u2010Z., Song, M.\u2010Y., Chen, W.\u2010X., Chen, Y.\u2010S., Tan, M.\u2010X., Guo, Y.\u2010W., Li, S.\u2010P. The chemokine CXCL1 and its receptor CXCR2 contribute to chronic stress\u2010induced depression in mice. FASEB J. 33, 8853\u20138864 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201802359rr","type":"journal-article","created":{"date-parts":[[2019,4,29]],"date-time":"2019-04-29T18:18:11Z","timestamp":1556561891000},"page":"8853-8864","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["The chemokine CXCL1 and its receptor CXCR2 contribute to chronic stress\u2010induced depression in mice"],"prefix":"10.1096","volume":"33","author":[{"given":"Hui\u2010Hui","family":"Chai","sequence":"first","affiliation":[{"name":"Department of Neurosurgery Dongguan People's Hospital Affiliated Dongguan People's Hospital of Southern Medical University  Dongguan 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