ArticleJournal of neuroinflammation2015
CXCR2 is essential for cerebral endothelial activation and leukocyte recruitment during neuroinflammation.
Article in Journal of neuroinflammation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 121 citations in OpenAlex.
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- The brain washing system in sepsis-associated encephalopathy.Journal of neuroinflammation · 2025Review
- Neutrophils-astrocyte interactions in central nervous system inflammation.Cell death & disease · 2025Review
- Multi-omics machine learning classifier and blood transcriptomic signature of Parkinson's disease.Research square · 2025Article
- NLRP3 activation induces BBB disruption and neutrophil infiltration via CXCR2 signaling in the mouse brain.Journal of neuroinflammation · 2025Article
- Optoacoustic imaging of the brain in a cachexia-inducing pancreatic cancer xenograft.Frontiers in oncology · 2025Article
- Leukocyte recruitment in flavivirus-induced encephalitis.Frontiers in immunology · 2025Review
- Article
- Rodent Model of Cardiopulmonary Bypass Demonstrates Systemic Inflammation and Neuromarker Changes.The Journal of surgical research · 2024Article
- Adverse effects of CXCR2 deficiency in mice reared under non-gnotobiotic conditions.Scientific reports · 2024Article
- Systemic inflammation following traumatic injury and its impact on neuroinflammatory gene expression in the rodent brain.Journal of neuroinflammation · 2024Article
- Identification and Validation of CXCL2 as a Key Gene for Childhood Obesity.Biochemical genetics · 2024Article
- Cerebral Endothelial CXCR2 Promotes Neutrophil Transmigration into Central Nervous System in LPS-Induced Septic Encephalopathy.Biomedicines · 2024Article
- Low-intensity pulsed ultrasound stimulation (LIPUS) modulates microglial activation following intracortical microelectrode implantation.Nature communications · 2024Article
- Transcriptional pathobiology and multi-omics predictors for Parkinson's disease.bioRxiv : the preprint server for biology · 2024Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundChemokines and chemokine receptors cooperate to promote immune cell recruitment to the central nervous system (CNS). In this study, we investigated the roles of CXCR2 and CXCL1 in leukocyte recruitment to the CNS using a murine model of neuroinflammation.
methodsWild-type (WT), CXCL1(-/-), and CXCR2(-/-) mice each received an intracerebroventricular (i.c.v.) injection of lipopolysaccharide (LPS). Esterase staining and intravital microscopy were performed to examine neutrophil recruitment to the brain. To assess endothelial activation in these mice, the expression of adhesion molecules was measured via quantitative real-time polymerase chain reaction (PCR) and Western blotting. To identify the cellular source of functional CXCR2, chimeric mice were generated by transferring bone marrow cells between the WT and CXCR2(-/-) mice.
resultsExpression levels of the chemokines CXCL1, CXCL2, and CXCL5 were significantly increased in the brain following the i.c.v. injection of LPS. CXCR2 or CXCL1 deficiency blocked neutrophil infiltration and leukocyte recruitment in the cerebral microvessels. In the CXCR2(-/-) and CXCL1(-/-) mice, the cerebral endothelial expression of adhesion molecules such as P-selectin and VCAM-1 was dramatically reduced. Furthermore, the bone marrow transfer experiments demonstrated that CXCR2 expression on CNS-residing cells is essential for cerebral endothelial activation and leukocyte recruitment. Compared with microglia, cultured astrocytes secreted a much higher level of CXCL1 in vitro. Astrocyte culture conditioned medium significantly increased the expression of VCAM-1 and ICAM-1 in cerebral endothelial cells in a CXCR2-dependent manner. Additionally, CXCR2 messenger RNA (mRNA) expression in cerebral endothelial cells but not in microglia or astrocytes was increased following tumor necrosis factor-α (TNF-α) stimulation. The intravenous injection of the CXCR2 antagonist SB225002 significantly inhibited endothelial activation and leukocyte recruitment to cerebral microvessels.
conclusionsCXCL1 secreted by astrocytes and endothelial CXCR2 play essential roles in cerebral endothelial activation and subsequent leukocyte recruitment during neuroinflammation.
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