Ethanol exposure suppresses bone marrow-derived dendritic cell inflammatory responses independent of TLR4 expression.
Acute alcohol (ethanol) exposure is linked with increased susceptibility to infection and increased mortality in trauma and burn patients. Dendritic cells (DCs) are central mediators in innate and adaptive immune responses, and they play a role in the presentation of pathogens to adaptive immune cells. We investigated the effects of acute ethanol exposure on bone marrow-derived DC (BM-DC) responses. Total bone marrow cells, obtained from 8 to 10 week old C57BL/6 male mice, were cultured in the presence of granulocyte/monocyte-colony stimulating factor and interleukin (IL)-4 for 7 days. BM-DCs were harvested and treated with increasing doses of ethanol (50, 100, and 250 mM) at the time of, or 3 h before, lipopolysaccharide (LPS). After LPS, supernatants were collected for cytokine measurement, and cells were harvested for flow cytometry. Concurrent acute ethanol exposure and LPS treatment resulted in a dose-dependent suppression of IL-6, IL-12p40, IL-23, and IL-10. In addition, ethanol exposure before LPS dysregulated the IL-12p40/IL-23 balance and more profoundly suppressed IL-6 and IL-10 secretion by BM-DCs, as compared with cells concurrently treated with ethanol and LPS. Ethanol treatment did not affect either toll-like receptor (TLR)4 or TLR2 expression. In summary, our study demonstrates that acute ethanol exposure suppresses BM-DC LPS-induced responses, irrespective of affecting TLR4 or TLR2 expression.
Health Sciences Division, Alcohol Research Program, Loyola University Chicago, Maywood, Illinois 60153, USA.
Juan L
JL
Rendon
Brian A
BA
Janda
Monica E
ME
Bianco
Mashkoor A
MA
Choudhry
D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D000431:Ethanol / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000276:immunology; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015847:Interleukin-4 / Q000276:immunology / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis* / Q000276:immunology
D002492:Central Nervous System Depressants; D008070:Lipopolysaccharides; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D015847:Interleukin-4; D000431:Ethanol