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Mediators of Inflammation
Volume 2014, Article ID 808695, 16 pages
http://dx.doi.org/10.1155/2014/808695
Research Article

Chronic Ethanol Feeding Modulates Inflammatory Mediators, Activation of Nuclear Factor-κB, and Responsiveness to Endotoxin in Murine Kupffer Cells and Circulating Leukocytes

1Department of Trauma, Hand and Reconstructive Surgery, J.W. Goethe University, 60590 Frankfurt/Main, Germany
2Department of Metabolic Physiology, J.W. Goethe University, 60439 Frankfurt/Main, Germany
3Department of General and Visceral Surgery, J.W. Goethe University, 60590 Frankfurt/Main, Germany
4Department of Medicine, Pharmacology and Immunology-Microbiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7290, USA

Received 30 July 2013; Revised 24 November 2013; Accepted 25 November 2013; Published 29 January 2014

Academic Editor: Elizabeth J. Kovacs

Copyright © 2014 Miriam Maraslioglu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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-κBEGFP 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-1β 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.