title: Transcriptome Profiling Reveals Disruption of Innate Immunity in Chronic Heavy Ethanol Consuming Female Rhesus Macaques.
abstract: It is well established that heavy ethanol consumption interferes with the immune system and inflammatory processes, resulting in increased risk for infectious and chronic diseases. However, these processes have yet to be systematically studied in a dose and sex-dependent manner. In this study, we investigated the impact of chronic heavy ethanol consumption on gene expression using RNA-seq in peripheral blood mononuclear cells isolated from female rhesus macaques with daily consumption of 4% ethanol available 22hr/day for 12 months resulting in average ethanol consumption of 4.3 g/kg/day (considered heavy drinking). Differential gene expression analysis was performed using edgeR and gene enrichment analysis using MetaCore™. We identified 1106 differentially expressed genes, meeting the criterion of ≥ two-fold change and p-value ≤ 0.05 in expression (445 up- and 661 down-regulated). Pathway analysis of the 879 genes with characterized identifiers showed that the most enriched gene ontology processes were "response to wounding", "blood coagulation", "immune system process", and "regulation of signaling". Changes in gene expression were seen despite the lack of differences in the frequency of any major immune cell subtype between ethanol and controls, suggesting that heavy ethanol consumption modulates gene expression at the cellular level rather than altering the distribution of peripheral blood mononuclear cells. Collectively, these observations provide mechanisms to explain the higher incidence of infection, delay in wound healing, and increase in cardiovascular disease seen in subjects with Alcohol use disorder.
authors.affiliation: Graduate Program in Genetics, Genomics and Bioinformatics, University of California Riverside, Riverside, California, United States of America.|Division of Biomedical Sciences, School of Medicine, University of California Riverside, Riverside, California, United States of America.
authors.forename: Suhas
authors.initials: S
authors.lastname: Sureshchandra
authors.affiliation: Division of Biomedical Sciences, School of Medicine, University of California Riverside, Riverside, California, United States of America.
authors.forename: Maham
authors.initials: M
authors.lastname: Rais
authors.affiliation: Division of Neurosciences, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, United States of America.
authors.forename: Cara
authors.initials: C
authors.lastname: Stull
authors.affiliation: Division of Neurosciences, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, United States of America.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Grant
authors.affiliation: Graduate Program in Genetics, Genomics and Bioinformatics, University of California Riverside, Riverside, California, United States of America.|Division of Biomedical Sciences, School of Medicine, University of California Riverside, Riverside, California, United States of America.|Division of Neurosciences, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, United States of America.
authors.forename: Ilhem
authors.initials: I
authors.lastname: Messaoudi
mesh_terms: D000818:Animals; D063425:Binge Drinking / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D001777:Blood Coagulation / Q000187:drug effects / Q000235:genetics; D004195:Disease Models, Animal; D000431:Ethanol / Q000009:adverse effects*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D063990:Gene Ontology; D007113:Immunity, Innate / Q000187:drug effects* / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008253:Macaca mulatta; D058977:Molecular Sequence Annotation; D012646:Self Administration; D017423:Sequence Analysis, RNA; D015398:Signal Transduction / Q000187:drug effects; D059467:Transcriptome; D014945:Wound Healing / Q000187:drug effects / Q000235:genetics
chemical_list: D000431:Ethanol