Activation of NF-κB after chronic ethanol intake and haemorrhagic shock/resuscitation in mice
| Autor: | Christian Jobin, C Nauck, Carolin Blattner, Mark Lehnert, S Korff, Roxane Weber, Dirk Henrich, Miriam Maraslioglu, Ingo Marzi |
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| Rok vydání: | 2013 |
| Předmět: |
Pharmacology
Liver injury medicine.medical_specialty Resuscitation Necrosis biology business.industry Inflammation NF-κB medicine.disease NFKB1 chemistry.chemical_compound Immune system Endocrinology chemistry Internal medicine Immunology biology.protein Medicine medicine.symptom business Interleukin 6 |
| Zdroj: | British Journal of Pharmacology. 170:506-518 |
| ISSN: | 0007-1188 |
| DOI: | 10.1111/bph.12224 |
| Popis: | Background and Purpose Chronic ethanol abuse and haemorrhagic shock are major causes of global mortality and, separately, induce profound hepato- and immune-toxic effects via activation of NF-κB. Here, we assessed the effects of chronic ethanol intake upon the pathophysiological derangements after haemorrhagic shock with subsequent resuscitation (H/R), with particular attention to the contribution of NF-κB. Experimental Approach Transgenic NF-κBEGFP mice, expressing the enhanced green fluorescent protein (EGFP) under the transcriptional control of NF-κB cis-elements were fed a Lieber-DeCarli diet containing ethanol (EtOH-diet) or an isocaloric control diet for 4 weeks and were then pairwise subjected to H/R. Liver tissues and peripheral blood were sampled at 2 or 24 h after H/R. Cytokines in blood and tissue and leukocyte activation (as CD11b expression) were measured, along with EGFP as a marker of NF-κB activation. Key Results The EtOH-diet increased mortality at 24 h after H/R and elevated liver injury, associated with an up-regulation of NF-κB-dependent genes and IL-6 release; it also increased production of NF-κB-driven intercellular adhesion molecule 1 (ICAM-1) and EGFP in liver tissue. At 2h after the H/R procedure in ethanol-fed mice we observed the highest proportion of NF-κB activated non-parenchymal cells and an NF-κB-dependent increase in polymorphonuclear leukocyte CD11b expression. Conclusions and Implications The EtOH-diet exacerbated liver injury after H/R, accompanying an overwhelming hepatic and systemic immune response. Our findings contribute to evidence implicating NF-κB as a key player in the orchestration of the immune response in haemorrhagic shock patients with a history of chronic ethanol abuse. |
| Databáze: | OpenAIRE |
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