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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Livne-Bar, Izhar Maurya, Shubham Gronert, Karsten Sivak, Jeremy M. |
| Abstract | Lipoxins are small lipids that are potent endogenous mediators of systemic inflammation resolution in a variety of diseases. We previously reported that Lipoxins A4 and B4 (LXA4 and LXB4) have protective activities against neurodegenerative injury. Yet, lipoxin activities and downstream signaling in neuroinflammatory processes are not well understood. Here, we utilized a model of posterior uveitis induced by lipopolysaccharide endotoxin (LPS), which results in rapid retinal neuroinflammation primarily characterized by activation of resident macroglia (astrocytes and Müller glia), and microglia. Using this model, we observed that each lipoxin reduces acute inner retinal inflammation by affecting endogenous glial responses in a cascading sequence beginning with astrocytes and then microglia, depending on the timing of exposure; prophylactic or therapeutic. Subsequent analyses of retinal cytokines and chemokines revealed inhibition of both CXCL9 (MIG) and CXCL10 (IP10) by each lipoxin, compared to controls, following LPS injection. CXCL9 and CXCL10 are common ligands for the CXCR3 chemokine receptor, which is prominently expressed in inner retinal astrocytes and ganglion cells. We found that CXCR3 inhibition reduces LPS-induced neuroinflammation, while CXCR3 agonism alone induces astrocyte reactivity. Together, these data uncover a novel lipoxin–CXCR3 pathway to promote distinct anti-inflammatory and proresolution cascades in endogenous retinal glia. |
| Related Links | https://jneuroinflammation.biomedcentral.com/counter/pdf/10.1186/s12974-024-03010-0.pdf |
| Ending Page | 13 |
| Page Count | 13 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 17422094 |
| DOI | 10.1186/s12974-024-03010-0 |
| Journal | Journal of Neuroinflammation |
| Issue Number | 1 |
| Volume Number | 21 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2024-01-11 |
| Access Restriction | Open |
| Subject Keyword | Neurosciences Neurology Neurobiology Immunology Lipoxins Retina Uveitis Neuroinflammation Inflammation resolution Gliosis CXCL9 CXCL10 CXCR3 |
| Content Type | Text |
| Resource Type | Article |
| Subject | Neuroscience Immunology Cellular and Molecular Neuroscience Neurology |
| Journal Impact Factor | 9.3/2023 |
| 5-Year Journal Impact Factor | 9.8/2023 |
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