Converging actions of alcohol on liver and brain immune signaling
Department of Medicine, Division of Gastroenterology
Digestive System Diseases | Gastroenterology | Hepatology | Immunopathology
Chronic excessive alcohol consumption results in inflammation in multiple organs, including the brain. While the contribution of neuroinflammation to alcohol-related cognitive dysfunction and behavioral alterations is established, the mechanisms by which alcohol triggers inflammation in the brain are only partially understood. There are acute and long-term alterations in brain function due to intercellular and intracellular changes of different cell types as a result of alcohol consumption. This review focuses on the alcohol-induced proinflammatory cellular and molecular changes in the central nervous system. Alcohol passes through the blood-brain barrier and alters neurotransmission. Alcohol use activates microglia and astrocyte, contributing to neurodegeneration and impaired regeneration. Alcohol-induced cell injury in the brain results in release of damage-associated molecular patterns, such as high mobility group box 1, that trigger inflammatory changes through activation of pattern recognition receptors. In addition, alcohol consumption increases intestinal permeability and results in increased levels of pathogen-associated molecular pattern such as endotoxin in the systemic circulation that triggers PRRs and inflammation. The Toll-like receptor-4 pathway that activates nuclear factor-kappaB and secretion of proinflammatory cytokines, tumor necrosis factor-alpha, interleukin-1-beta, and chemokines, including monocyte chemotactic protein-1, has been suggested to contribute to alcohol-induced neuroinflammation. Alcohol-induced IL-1beta secretion also requires Nod-like receptor-mediated inflammasome and caspase-1 activation, and, consistent with this, disruption of IL-1/IL-1-receptor signaling prevents alcohol-induced neuroinflammation. Delicate regulators of inflammatory gene expressions are micro-RNAs (miRs) that have recently been identified in alcohol-related neuroinflammation. Alcohol induces miR155, a regulator of inflammation in the brain, and deficiency in miR-155 in mice was protective from neuroinflammatory changes. These observations suggest that manipulation of miR pathways and cytokine induction may reduce alcohol-induced proinflammatory processes.
DOI of Published Version
Int Rev Neurobiol. 2014;118:359-80. doi: 10.1016/B978-0-12-801284-0.00011-7. Link to article on publisher's site
International review of neurobiology
Szabo, Gyongyi and Lippai, Dora, "Converging actions of alcohol on liver and brain immune signaling" (2014). Gastroenterology Publications and Presentations. 132.