| First Author | Rutkowska A | Year | 2018 |
| Journal | Neuropharmacology | Volume | 133 |
| Pages | 121-128 | PubMed ID | 29374507 |
| Mgi Jnum | J:323877 | Mgi Id | MGI:6878851 |
| Doi | 10.1016/j.neuropharm.2018.01.029 | Citation | Rutkowska A, et al. (2018) EBI2 regulates pro-inflammatory signalling and cytokine release in astrocytes. Neuropharmacology 133:121-128 |
| abstractText | The endogenous oxysterol 7alpha, 25-dihydroxycholesterol (7alpha25HC) ligand activates the G protein-coupled receptor EBI2 to regulate T cell-dependant antibody response and B cell migration. We have demonstrated that EBI2 is expressed in human and mouse astrocytes, that 7alpha25HC induces intracellular signalling and astrocyte migration, and that EBI2 plays a role in the crosstalk between astrocytes and macrophages. Recently, we demonstrate that EBI2 regulates myelin development and inhibits LPC-induced demyelination. Here, we show that 7alpha25HC inhibits LPS- and IL17/TNF-induced pro-inflammatory cytokine release in astrocytes. We observe the following: 1. Human astrocytes treated with IL17/TNF increases the nuclear translocation of NFkappaB, which is attenuated by pre-treatment with 7alpha25HC; 2. IL17/TNF increases cell impedance in human astrocytes, which is also attenuated by pre-treatment with 7alpha25HC; 3. The EBI2 antagonist NIBR189 inhibits these effects of 7alpha25HC, supporting the role of EBI2; 4. in vivo data corroborate these in vitro findings, showing that EBI2 knock-out (KO) animals display enhanced pro-inflammatory cytokine in response to LPS challenge, in the brain. These results demonstrate a role for oxysterol/EBI2 signalling in attenuating the response of astrocytes to pro-inflammatory signals as well as limiting the levels of pro-inflammatory cytokines in the brain. |
