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Epigenetic targets for reversing immune defects caused by alcohol exposure.

Curtis BJ, Zahs A, Kovacs EJ - Alcohol Res (2013)

Bottom Line: Epigenetic mechanisms play a pivotal role in these processes.In addition, epigenetic mechanisms may underlie alcohol's ability to interfere with the barrier functions of the gut and respiratory systems, which also contribute to the heightened risk of infections.Better understanding of alcohol's effects on these epigenetic processes may help researchers identify new targets for the development of novel medications to prevent or ameliorate alcohol's detrimental effects on the immune system.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Burn & Shock Trauma Institute, Loyola University, Chicago, Illinois, USA.

ABSTRACT
Alcohol consumption alters factors that modify gene expression without changing the DNA code (i.e., epigenetic modulators) in many organ systems, including the immune system. Alcohol enhances the risk for developing several serious medical conditions related to immune system dysfunction, including acute respiratory distress syndrome (ARDS), liver cancer, and alcoholic liver disease (ALD). Binge and chronic drinking also render patients more susceptible to many infectious pathogens and advance the progression of HIV infection by weakening both innate and adaptive immunity. Epigenetic mechanisms play a pivotal role in these processes. For example, alcohol-induced epigenetic variations alter the developmental pathways of several types of immune cells (e.g., granulocytes, macrophages, and T-lymphocytes) and through these and other mechanisms promote exaggerated inflammatory responses. In addition, epigenetic mechanisms may underlie alcohol's ability to interfere with the barrier functions of the gut and respiratory systems, which also contribute to the heightened risk of infections. Better understanding of alcohol's effects on these epigenetic processes may help researchers identify new targets for the development of novel medications to prevent or ameliorate alcohol's detrimental effects on the immune system.

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Chronic alcohol consumption skews macrophage polarization toward an M1 (i.e., pro-inflammatory) phenotype, leading to excessive or prolonged inflammation. Two approaches using epigenetic modulators—microRNA 155 (miR-155) and histone deacetylase inhibitors—can potentionally reverse protein translation or gene transcription of M1 pro-inflammatory cytokines. Another type of enzyme—histone lysine (H3K27) demethylases—increase transcription of M2 anti-inflammatory cytokines. Factors that increase protein levels or enhance activity of H3K27 demethylases therefore may potentially be utilized to promote M2 polarization.
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f2-arcr-35-1-97: Chronic alcohol consumption skews macrophage polarization toward an M1 (i.e., pro-inflammatory) phenotype, leading to excessive or prolonged inflammation. Two approaches using epigenetic modulators—microRNA 155 (miR-155) and histone deacetylase inhibitors—can potentionally reverse protein translation or gene transcription of M1 pro-inflammatory cytokines. Another type of enzyme—histone lysine (H3K27) demethylases—increase transcription of M2 anti-inflammatory cytokines. Factors that increase protein levels or enhance activity of H3K27 demethylases therefore may potentially be utilized to promote M2 polarization.

Mentions: After challenge to the immune system occurs (e.g., an infection), macrophages are generated by the maturation of precursor cells called monocytes. During this process, the macrophages can become either M1 or M2 macrophages; this is called macrophage polarization. The ratio of M1 to M2 macrophages changes depending on the presence of a variety of factors; this variability is known as macrophage plasticity and allows the organism to modulate the immune response. Accordingly, controlling macrophage plasticity is critical to first battle pathogens and then resolve the resulting inflammation to prevent tissue damage. Alcohol exposure skews macrophage polarization towards M1 (i.e., towards inflammation) in the liver (Louvet et al. 2011; Mandal et al. 2011), resulting in deleterious consequences (figure 2).


Epigenetic targets for reversing immune defects caused by alcohol exposure.

Curtis BJ, Zahs A, Kovacs EJ - Alcohol Res (2013)

Chronic alcohol consumption skews macrophage polarization toward an M1 (i.e., pro-inflammatory) phenotype, leading to excessive or prolonged inflammation. Two approaches using epigenetic modulators—microRNA 155 (miR-155) and histone deacetylase inhibitors—can potentionally reverse protein translation or gene transcription of M1 pro-inflammatory cytokines. Another type of enzyme—histone lysine (H3K27) demethylases—increase transcription of M2 anti-inflammatory cytokines. Factors that increase protein levels or enhance activity of H3K27 demethylases therefore may potentially be utilized to promote M2 polarization.
© Copyright Policy - public-domain
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3860427&req=5

f2-arcr-35-1-97: Chronic alcohol consumption skews macrophage polarization toward an M1 (i.e., pro-inflammatory) phenotype, leading to excessive or prolonged inflammation. Two approaches using epigenetic modulators—microRNA 155 (miR-155) and histone deacetylase inhibitors—can potentionally reverse protein translation or gene transcription of M1 pro-inflammatory cytokines. Another type of enzyme—histone lysine (H3K27) demethylases—increase transcription of M2 anti-inflammatory cytokines. Factors that increase protein levels or enhance activity of H3K27 demethylases therefore may potentially be utilized to promote M2 polarization.
Mentions: After challenge to the immune system occurs (e.g., an infection), macrophages are generated by the maturation of precursor cells called monocytes. During this process, the macrophages can become either M1 or M2 macrophages; this is called macrophage polarization. The ratio of M1 to M2 macrophages changes depending on the presence of a variety of factors; this variability is known as macrophage plasticity and allows the organism to modulate the immune response. Accordingly, controlling macrophage plasticity is critical to first battle pathogens and then resolve the resulting inflammation to prevent tissue damage. Alcohol exposure skews macrophage polarization towards M1 (i.e., towards inflammation) in the liver (Louvet et al. 2011; Mandal et al. 2011), resulting in deleterious consequences (figure 2).

Bottom Line: Epigenetic mechanisms play a pivotal role in these processes.In addition, epigenetic mechanisms may underlie alcohol's ability to interfere with the barrier functions of the gut and respiratory systems, which also contribute to the heightened risk of infections.Better understanding of alcohol's effects on these epigenetic processes may help researchers identify new targets for the development of novel medications to prevent or ameliorate alcohol's detrimental effects on the immune system.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Burn & Shock Trauma Institute, Loyola University, Chicago, Illinois, USA.

ABSTRACT
Alcohol consumption alters factors that modify gene expression without changing the DNA code (i.e., epigenetic modulators) in many organ systems, including the immune system. Alcohol enhances the risk for developing several serious medical conditions related to immune system dysfunction, including acute respiratory distress syndrome (ARDS), liver cancer, and alcoholic liver disease (ALD). Binge and chronic drinking also render patients more susceptible to many infectious pathogens and advance the progression of HIV infection by weakening both innate and adaptive immunity. Epigenetic mechanisms play a pivotal role in these processes. For example, alcohol-induced epigenetic variations alter the developmental pathways of several types of immune cells (e.g., granulocytes, macrophages, and T-lymphocytes) and through these and other mechanisms promote exaggerated inflammatory responses. In addition, epigenetic mechanisms may underlie alcohol's ability to interfere with the barrier functions of the gut and respiratory systems, which also contribute to the heightened risk of infections. Better understanding of alcohol's effects on these epigenetic processes may help researchers identify new targets for the development of novel medications to prevent or ameliorate alcohol's detrimental effects on the immune system.

Show MeSH
Related in: MedlinePlus