Chronic Ethanol Feeding Modulates Inflammatory Mediators, Activation of Nuclear Factor-κB, and Responsiveness to Endotoxin in Murine Kupffer Cells and Circulating Leukocytes
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,...
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| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2014-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2014/808695 |
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| author | Miriam Maraslioglu Elsie Oppermann Carolin Blattner Roxane Weber Dirk Henrich Christian Jobin Elke Schleucher Ingo Marzi Mark Lehnert |
| author_facet | Miriam Maraslioglu Elsie Oppermann Carolin Blattner Roxane Weber Dirk Henrich Christian Jobin Elke Schleucher Ingo Marzi Mark Lehnert |
| author_sort | Miriam Maraslioglu |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-3998c16850dd494b9a7c86e372af5295 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-3998c16850dd494b9a7c86e372af52952025-02-03T01:31:23ZengWileyMediators of Inflammation0962-93511466-18612014-01-01201410.1155/2014/808695808695Chronic Ethanol Feeding Modulates Inflammatory Mediators, Activation of Nuclear Factor-κB, and Responsiveness to Endotoxin in Murine Kupffer Cells and Circulating LeukocytesMiriam Maraslioglu0Elsie Oppermann1Carolin Blattner2Roxane Weber3Dirk Henrich4Christian Jobin5Elke Schleucher6Ingo Marzi7Mark Lehnert8Department of Trauma, Hand and Reconstructive Surgery, J.W. Goethe University, 60590 Frankfurt/Main, GermanyDepartment of General and Visceral Surgery, J.W. Goethe University, 60590 Frankfurt/Main, GermanyDepartment of Trauma, Hand and Reconstructive Surgery, J.W. Goethe University, 60590 Frankfurt/Main, GermanyDepartment of Trauma, Hand and Reconstructive Surgery, J.W. Goethe University, 60590 Frankfurt/Main, GermanyDepartment of Trauma, Hand and Reconstructive Surgery, J.W. Goethe University, 60590 Frankfurt/Main, GermanyDepartment of Medicine, Pharmacology and Immunology-Microbiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7290, USADepartment of Metabolic Physiology, J.W. Goethe University, 60439 Frankfurt/Main, GermanyDepartment of Trauma, Hand and Reconstructive Surgery, J.W. Goethe University, 60590 Frankfurt/Main, GermanyDepartment of Trauma, Hand and Reconstructive Surgery, J.W. Goethe University, 60590 Frankfurt/Main, GermanyChronic 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.http://dx.doi.org/10.1155/2014/808695 |
| spellingShingle | Miriam Maraslioglu Elsie Oppermann Carolin Blattner Roxane Weber Dirk Henrich Christian Jobin Elke Schleucher Ingo Marzi Mark Lehnert Chronic Ethanol Feeding Modulates Inflammatory Mediators, Activation of Nuclear Factor-κB, and Responsiveness to Endotoxin in Murine Kupffer Cells and Circulating Leukocytes Mediators of Inflammation |
| title | Chronic Ethanol Feeding Modulates Inflammatory Mediators, Activation of Nuclear Factor-κB, and Responsiveness to Endotoxin in Murine Kupffer Cells and Circulating Leukocytes |
| title_full | Chronic Ethanol Feeding Modulates Inflammatory Mediators, Activation of Nuclear Factor-κB, and Responsiveness to Endotoxin in Murine Kupffer Cells and Circulating Leukocytes |
| title_fullStr | Chronic Ethanol Feeding Modulates Inflammatory Mediators, Activation of Nuclear Factor-κB, and Responsiveness to Endotoxin in Murine Kupffer Cells and Circulating Leukocytes |
| title_full_unstemmed | Chronic Ethanol Feeding Modulates Inflammatory Mediators, Activation of Nuclear Factor-κB, and Responsiveness to Endotoxin in Murine Kupffer Cells and Circulating Leukocytes |
| title_short | Chronic Ethanol Feeding Modulates Inflammatory Mediators, Activation of Nuclear Factor-κB, and Responsiveness to Endotoxin in Murine Kupffer Cells and Circulating Leukocytes |
| title_sort | chronic ethanol feeding modulates inflammatory mediators activation of nuclear factor κb and responsiveness to endotoxin in murine kupffer cells and circulating leukocytes |
| url | http://dx.doi.org/10.1155/2014/808695 |
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