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| Content Provider | Springer Nature Link |
|---|---|
| Author | Alfonso Loeches, Silvia Ureña Peralta, Juan Morillo Bargues, Mª José Gómez Pinedo, Ulises Guerri, Consuelo |
| Copyright Year | 2015 |
| Abstract | We reported that the ethanol-induced innate immune response by activating TLR4 signaling triggers gliosis and neuroinflammation. Ethanol also activates other immune receptors, such as NOD-like-receptors, and specifically NLRP3-inflammasome in astroglial cells, to stimulate caspase-1 cleavage and IL-1β and IL-18 cytokines production. Yet, whether microglia NLRs are also sensitive to the ethanol effects that contribute to neuroinflammation is uncertain. Using cerebral cortexes of the chronic alcohol-fed WT and TLR4$^{−/−}$ mice, we demonstrated that chronic ethanol treatment enhanced TLR4 mediated-NLRP3/Caspase-1 complex activation, and up-regulated pro-inflammatory cytokines and chemokines levels. Ethanol-induced NLRP3-inflammasome activation and mitochondria-ROS generation were also observed in cultured microglial cells. The up-regulation of CD45$^{high}$/CD11b$^{+}$ cell populations and matrix metalloproteinase-9 levels was also noted in the cortexes of the ethanol-treated WT mice. Notably, elimination of the TLR4 function abolished most ethanol-induced neuroinflammatory effects. Thus, our results demonstrate that ethanol triggers TLR4-mediated NLRP3-inflammasome activation in glial cells, and suggest that microglia stimulation may compromise the permeability of blood–brain barrier events to contribute to ethanol-induced neuroinflammation and brain damage. |
| Starting Page | 193 |
| Ending Page | 209 |
| Page Count | 17 |
| File Format | |
| ISSN | 03643190 |
| Journal | Neurochemical Research |
| Volume Number | 41 |
| Issue Number | 1-2 |
| e-ISSN | 15736903 |
| Language | English |
| Publisher | Springer US |
| Publisher Date | 2015-11-11 |
| Publisher Place | New York |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | TLR4 Alcohol Microglia Leukocyte infiltration Matrix metalloproteinase BBB Neurosciences Neurochemistry Biochemistry Cell Biology Neurology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Medicine Biochemistry Cellular and Molecular Neuroscience |
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