Implications of ER Stress, the Unfolded Protein Response, and Pro- and Anti-Apoptotic Protein Fingerprints in Human Monocyte-Derived Dendritic Cells Treated With Alcohol

Biomedical Proteomics Facility, Department of Microbiology and Immunology, Universidad Central del Caribe School of Medicine, Bayamón, Puerto Rico, USA.
Alcoholism Clinical and Experimental Research (Impact Factor: 3.21). 12/2010; 34(12):2081-8. DOI: 10.1111/j.1530-0277.2010.01304.x
Source: PubMed


Dendritic cells (DCs) are responsible for the activation of T cells and B cells. There is accumulating evidence that psychoactive substances such as alcohol can affect immune responses. We hypothesize that this occurs by modulating changes in proteins triggering a process known as unfolded protein response (UPR). This process protects cells from the toxic effects of misfolded proteins responsible for causing endoplasmic reticulum (ER) stress. Although much is known about ER stress, little is understood about the consequences of ethanol use on DC's protein expression.
In this study, we investigated alterations in the proteins of human monocyte-derived dendritic cells (MDDC) treated with 0.1% of alcohol by two-dimensional (2D) gel electrophoresis followed by liquid chromatography-tandem mass spectrometry, protein identification, and confirmation at the gene expression level by qRT-PCR.
Proteomes of related samples demonstrated 32 differentially expressed proteins that had a 2-fold or greater change in expression (18 spots were up-regulated and 14 were down-regulated), compared to the control cultures (untreated cells). Alcohol significantly changed the expression of several components of the UPR stress-induced pathways that include chaperones, ER stress, antioxidant enzymes, proteases, alcohol dehydrogenase, cytoskeletal and apoptosis-regulating proteins. qRT-PCR analyses highlighted the enhanced expression of UPR and antioxidant genes that increased (18 hours) with alcohol treatment.
Results of these analyses provide insights into alcohol mechanisms of regulating DC and suggest that alcohol induced specifically the UPR in DC. We speculate that activation of a UPR by alcohol may protect the DC from oxidant injury but may lead to the development of alcohol-related diseases.

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Available from: Nawal Boukli, Nov 17, 2015
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    • "The role of immune-related genes in alcohol dependence is also supported by genetic association studies and transcriptome meta-analysis in peripheral human cells (Boukli et al., 2010), postmortem brains of alcoholics (Liu et al., 2006; Okvist et al., 2007; Ponomarev, Wang, Zhang, Harris, & Mayfield, 2012), drinking models in mice (Gorini, Nunez, & Mayfield, 2013; Gorini, Roberts, & Mayfield, 2013; Nunez et al., 2013; Osterndorff- Kahanek et al., 2013), and vapor models for alcohol dependence in mice (Gorini, Nunez, et al., 2013; Gorini, Roberts, et al., 2013). Many immune-associated genes that are differentially expressed in brains of ethanol-treated mice are also differentially expressed in brains of human alcoholics. "
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