Ethanol activates immune response in lymphoblastoid cells

Jeanette McClintick, Jay A. Tischfield, Li Deng, Manav Kapoor, Xiaoling Xuei, Howard Edenberg

Research output: Contribution to journalArticle

Abstract

The short-term effects of alcohol on gene expression in brain tissue cannot directly be studied in humans. Because neuroimmune signaling is altered by alcohol, immune cells are a logical, accessible choice to study and may provide biomarkers. RNAseq was used to study the effects of 48-h exposure to ethanol on lymphoblastoid cell lines (LCLs) from 20 alcoholic subjects and 20 control subjects. Ethanol exposure resulted in differential expression of 4456 of the 12,503 genes detectably expressed in the LCLs (FDR [false discovery rate] ≤ 0.05); 52% of these showed increased expression. Cells from alcoholic subjects and control subjects responded similarly. The genes whose expression changed fell into many pathways: NFκB, neuroinflammation, IL6, IL2, IL8, and dendritic cell maturation pathways were activated, consistent with increased signaling by NFκB, TNF, IL1, IL4, IL18, TLR4, and LPS. Signaling by Interferons A and B decreased, as did EIF2 signaling, phospholipase C signaling, and glycolysis. Baseline gene expression patterns were similar in LCLs from alcoholic subjects and control subjects. At relaxed stringency (p < 0.05), 465 genes differed, 230 of which were also affected by ethanol. There was a suggestion of compensation because baseline differences (no ethanol) were in the opposite direction of differences due to ethanol exposure in 78% of these genes. Pathways with IL8, phospholipase C, and α-adrenergic signaling were significant. The pattern of expression was consistent with increased signaling by several cytokines, including interferons, TLR2, and TLR3 in alcoholics. Expression of genes in the cholesterol biosynthesis pathway, including the rate-limiting enzyme HMGCR, was lower in alcoholic subjects. LCLs show many effects of ethanol exposure, some of which might provide biomarkers for alcohol use disorders. Identifying genes and pathways altered by ethanol can aid in interpreting which genes within loci identified by GWAS might play functional roles.

Original languageEnglish (US)
Pages (from-to)81-91
Number of pages11
JournalAlcohol
Volume79
DOIs
StatePublished - Sep 1 2019

Fingerprint

Ethanol
Alcoholics
alcoholism
Genes
Gene expression
Gene Expression
Cell Line
alcohol
Alcohols
Type C Phospholipases
Biomarkers
Interleukin-8
Interferons
Eukaryotic Initiation Factor-2
Interleukin-18
Genome-Wide Association Study
Biosynthesis
Glycolysis
Interleukin-4
Adrenergic Agents

Keywords

  • Alcohol dependence
  • Gene expression
  • Lymphoblastoid cell lines
  • Neuroimmune
  • RNA sequencing

ASJC Scopus subject areas

  • Health(social science)
  • Biochemistry
  • Toxicology
  • Neurology
  • Behavioral Neuroscience

Cite this

Ethanol activates immune response in lymphoblastoid cells. / McClintick, Jeanette; Tischfield, Jay A.; Deng, Li; Kapoor, Manav; Xuei, Xiaoling; Edenberg, Howard.

In: Alcohol, Vol. 79, 01.09.2019, p. 81-91.

Research output: Contribution to journalArticle

McClintick, Jeanette ; Tischfield, Jay A. ; Deng, Li ; Kapoor, Manav ; Xuei, Xiaoling ; Edenberg, Howard. / Ethanol activates immune response in lymphoblastoid cells. In: Alcohol. 2019 ; Vol. 79. pp. 81-91.
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