Next Article in Journal
Physiological Correlates of Moral Decision-Making in the Professional Domain
Next Article in Special Issue
C57BL/6 Substrain Differences in Pharmacological Effects after Acute and Repeated Nicotine Administration
Previous Article in Journal
Infant Understanding of Different Forms of Social Exclusion
Previous Article in Special Issue
Genetic Relationships Between Ethanol-Induced Conditioned Place Aversion and Other Ethanol Phenotypes in 15 Inbred Mouse Strains
Open AccessArticle

Ethanol Induction of Innate Immune Signals Across BV2 Microglia and SH-SY5Y Neuroblastoma Involves Induction of IL-4 and IL-13

1
Bowles Center for Alcohol Studies, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
2
Curriculum in Neurobiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
3
Department of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
4
Department of Psychiatry, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
*
Author to whom correspondence should be addressed.
Brain Sci. 2019, 9(9), 228; https://doi.org/10.3390/brainsci9090228
Received: 23 August 2019 / Revised: 3 September 2019 / Accepted: 8 September 2019 / Published: 10 September 2019
Innate immune signaling molecules, such as Toll-like receptors (TLRs), cytokines and transcription factor NFκB, are increased in post-mortem human alcoholic brain and may play roles in alcohol dependence and neurodegeneration. Innate immune signaling involves microglia -neuronal signaling which while poorly understood, may impact learning and memory. To investigate mechanisms of ethanol induction of innate immune signaling within and between brain cells, we studied immortalized BV2 microglia and SH-SY5Y human neuroblastoma to model microglial and neuronal signaling. Cells were treated alone or in co-culture using a Transwell system, which allows transfer of soluble mediators. We determined immune signaling mRNA using real-time polymerase chain reaction. Ethanol induced innate immune genes in both BV2 and SH-SY5Y cultured alone, with co-culture altering gene expression at baseline and following ethanol exposure. Co-culture blunted ethanol-induced high mobility group box protein 1 (HMGB1)-TLR responses, corresponding with reduced ethanol induction of several proinflammatory NFκB target genes. In contrast, co-culture resulted in ethanol upregulation of cytokines IL-4 and IL-13 in BV2 and corresponding receptors, that is, IL-4 and IL-13 receptors, in SH-SY5Y, suggesting induction of a novel signaling pathway. Co-culture reduction in HMGB1-TLR levels occurs in parallel with reduced proinflammatory gene induction and increased IL-4 and IL-13 ligands and receptors. Findings from these immortalized and tumor-derived cell lines could provide insight into microglial-neuronal interactions via release of soluble mediators in vivo. View Full-Text
Keywords: microglia; neurons; ethanol; innate immune; co-culture microglia; neurons; ethanol; innate immune; co-culture
Show Figures

Figure 1

MDPI and ACS Style

Lawrimore, C.J.; Coleman, L.G.; Zou, J.; Crews, F.T. Ethanol Induction of Innate Immune Signals Across BV2 Microglia and SH-SY5Y Neuroblastoma Involves Induction of IL-4 and IL-13. Brain Sci. 2019, 9, 228.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop