title: Chronic ethanol feeding modulates inflammatory mediators, activation of nuclear factor-κB, and responsiveness to endotoxin in murine Kupffer cells and circulating leukocytes.
abstract: Chronic ethanol abuse is known to increase susceptibility to infections after injury, in part, by modification of macrophage function. Several intracellular signalling mechanisms are involved in the initiation of inflammatory responses, including the nuclear factor-κB (NF-κB) pathway. In this study, we investigated the systemic and hepatic effect of chronic ethanol feeding on in vivo activation of NF-κB in NF-κB(EGFP) reporter gene mice. Specifically, the study focused on Kupffer cell proinflammatory cytokines IL-6 and TNF-α and activation of NF-κB after chronic ethanol feeding followed by in vitro stimulation with lipopolysaccharide (LPS). We found that chronic ethanol upregulated NF-κB activation and increased hepatic and systemic proinflammatory cytokine levels. Similarly, LPS-stimulated IL-1 β release from whole blood was significantly enhanced in ethanol-fed mice. However, LPS significantly increased IL-6 and TNF-α levels. These results demonstrate that chronic ethanol feeding can improve the responsiveness of macrophage LPS-stimulated IL-6 and TNF-α production and indicate that this effect may result from ethanol-induced alterations in intracellular signalling through NF-κB. Furthermore, LPS and TNF-α stimulated the gene expression of different inflammatory mediators, in part, in a NF-κB-dependent manner.
authors.affiliation: Department of Trauma, Hand and Reconstructive Surgery, J.W. Goethe University, 60590 Frankfurt/Main, Germany ; Department of Metabolic Physiology, J.W. Goethe University, 60439 Frankfurt/Main, Germany.
authors.forename: Miriam
authors.identifier: 0000-0002-2071-2801
authors.initials: M
authors.lastname: Maraslioglu
authors.affiliation: Department of General and Visceral Surgery, J.W. Goethe University, 60590 Frankfurt/Main, Germany.
authors.forename: Elsie
authors.initials: E
authors.lastname: Oppermann
authors.affiliation: Department of Trauma, Hand and Reconstructive Surgery, J.W. Goethe University, 60590 Frankfurt/Main, Germany ; Department of Metabolic Physiology, J.W. Goethe University, 60439 Frankfurt/Main, Germany.
authors.forename: Carolin
authors.identifier: 0000-0003-3138-7175
authors.initials: C
authors.lastname: Blattner
authors.affiliation: Department of Trauma, Hand and Reconstructive Surgery, J.W. Goethe University, 60590 Frankfurt/Main, Germany.
authors.forename: Roxane
authors.identifier: 0000-0002-3632-423X
authors.initials: R
authors.lastname: Weber
authors.affiliation: Department of Trauma, Hand and Reconstructive Surgery, J.W. Goethe University, 60590 Frankfurt/Main, Germany.
authors.forename: Dirk
authors.identifier: 0000-0002-9728-4032
authors.initials: D
authors.lastname: Henrich
authors.affiliation: Department of Medicine, Pharmacology and Immunology-Microbiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7290, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Jobin
authors.affiliation: Department of Metabolic Physiology, J.W. Goethe University, 60439 Frankfurt/Main, Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Schleucher
authors.affiliation: Department of Trauma, Hand and Reconstructive Surgery, J.W. Goethe University, 60590 Frankfurt/Main, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Marzi
authors.affiliation: Department of Trauma, Hand and Reconstructive Surgery, J.W. Goethe University, 60590 Frankfurt/Main, Germany.
authors.forename: Mark
authors.identifier: 0000-0002-8217-7066
authors.initials: M
authors.lastname: Lehnert
mesh_terms: D000428:Alcohol Drinking; D000818:Animals; D004731:Endotoxins / Q000737:chemistry*; D000431:Ethanol / Q000737:chemistry*; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007249:Inflammation; D015850:Interleukin-6 / Q000378:metabolism; D007728:Kupffer Cells / Q000166:cytology*; D007962:Leukocytes / Q000166:cytology*; D008070:Lipopolysaccharides / Q000737:chemistry; D008099:Liver / Q000378:metabolism; D008264:Macrophages / Q000166:cytology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism*; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D004731:Endotoxins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C577686:interleukin-6, mouse; D049452:Green Fluorescent Proteins; D000431:Ethanol