The DOI matches its Crossref record; 17 of the 17 references it cites were found in a registry or an index.
Alcohol-induced IL-1β in the brain is mediated by NLRP3/ASC inflammasome activation that amplifies neuroinflammation
Open accessAbstract
Alcohol-induced neuroinflammation is mediated by proinflammatory cytokines, including IL-1β. IL-1β production requires caspase-1 activation by inflammasomes—multiprotein complexes that are assembled in response to danger signals. We hypothesized that alcohol-induced inflammasome activation contributes to increased IL-1β in the brain. WT and TLR4-, NLRP3-, and ASC-deficient (KO) mice received an ethanol-containing or isocaloric control diet for 5 weeks, and some received the rIL-1ra, anakinra, or saline treatment. Inflammasome activation, proinflammatory cytokines, endotoxin, and HMGB1 were measured in the cerebellum. Expression of inflammasome components (NLRP1, NLRP3, ASC) and proinflammatory cytokines (TNF-α, MCP-1) was increased in brains of alcohol-fed compared with control mice. Increased caspase-1 activity and IL-1β protein in ethanol-fed mice indicated inflammasome activation. TLR4 deficiency protected from TNF-α, MCP-1, and attenuated alcohol-induced IL-1β increases. The TLR4 ligand, LPS, was not increased in the cerebellum. However, we found up-regulation of acetylated and phosphorylated HMGB1 and increased expression of the HMGB1 receptors (TLR2, TLR4, TLR9, RAGE) in alcohol-fed mice. NLRP3- or ASC-deficient mice were protected from caspase-1 activation and alcohol-induced IL-1β increase in the brain. Furthermore, in vivo treatment with rIL-1ra prevented alcohol-induced inflammasome activation and IL-1β, TNF-α, and acetylated HMGB1 increases in the cerebellum. Conversely, intracranial IL-1β administration induced TNF-α and MCP-1 in the cerebellum. In conclusion, alcohol up-regulates and activates the NLRP3/ASC inflammasome, leading to caspase-1 activation and IL-1β increase in the cerebellum. IL-1β amplifies neuroinflammation, and disruption of IL-1/IL-1R signaling prevents alcohol-induced inflammasome activation and neuroinflammation. Increased levels of acetylated and phosphorylated HMGB1 may contribute to alcoholic neuroinflammation.
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Cites
The NALP3 inflammasome is involved in the innate immune response to amyloid-β
Halle, A., Hornung, V., Petzold, G. C., Stewart, C. R., Monks, B. G., Reinheckel, T., Fitzgerald, K. A., Latz, E., Moore, K. J., & Golenbock, D. T. (2008) · Nature Immunology · doi:10.1038/ni.1636 · Cited by 2,441
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HMGB1: Endogenous Danger Signaling
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IL-1 receptor antagonist ameliorates inflammasome-dependent alcoholic steatohepatitis in mice
Petrasek, J., Bala, S., Csak, T., Lippai, D., Kodys, K., Menashy, V., Barrieau, M., Min, S.-Y., Kurt-Jones, E. A., & Szabo, G. (2012) · Journal of Clinical Investigation · doi:10.1172/jci60777 · Cited by 735
Self-citationInside, outside, upside down: damage-associated molecular-pattern molecules (DAMPs) and redox
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Cited by
Kang, R., Chen, R., Zhang, Q., Hou, W., Wu, S., Cao, L., Huang, J., Yu, Y., Fan, X.-G., Yan, Z., et al. (2014) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2014.05.001 · Cited by 956
Momen-Heravi, F., Bala, S., Kodys, K., & Szabo, G. (2015) · Scientific Reports · doi:10.1038/srep09991 · Cited by 347
Self-citationThe role of neuroimmune signaling in alcoholism
Crews, F. T., Lawrimore, C. J., Walter, T. J., & Coleman, L. G. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2017.01.031 · Cited by 321
Fann, D. Y.-W., Lim, Y.-A., Cheng, Y.-L., Lok, K.-Z., Chunduri, P., Baik, S.-H., Drummond, G. R., Dheen, S. T., Sobey, C. G., Jo, D.-G., et al. (2018) · Molecular Neurobiology · doi:10.1007/s12035-017-0394-9 · Cited by 309
Leclercq, S., Le Roy, T., Furgiuele, S., Coste, V., Bindels, L. B., Leyrolle, Q., Neyrinck, A. M., Quoilin, C., Amadieu, C., Petit, G., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108238 · Cited by 178
Metadata
- Authors
- Lippai, D., Bala, S., Petrasek, J., Csak, T., Levin, I., Kurt-Jones, E. A., & Szabo, G.
- Venue
- Journal of Leukocyte Biology
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-04-26
- Volume
- 94
- Issue
- 1
- Pages
- 171-182
- ISSN
- 0741-5400 (ISSN-L)
- 1938-3673
- OpenAlex
- W2144241574
- Cited by
- 215
- References
- 17
- FWCI
- 6.46
- Type
- journal article
- Language
- en
- Open access
- green
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- Lippai, D., Bala, S., Petrasek, J., Csak, T., Levin, I., Kurt-Jones, E. A., & Szabo, G. (2013). Alcohol-induced IL-1β in the brain is mediated by NLRP3/ASC inflammasome activation that amplifies neuroinflammation. Journal of Leukocyte Biology. https://doi.org/10.1189/jlb.1212659
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