Weiss, Thomas S. and Lupke, Madeleine and Dayoub, Rania and Geissler, Edward K. and Schlitt, Hans J. and Melter, Michael and Eggenhofer, Elke (2019) Augmenter of Liver Regeneration Reduces Ischemia Reperfusion Injury by Less Chemokine Expression, Gr-1 Infiltration and Oxidative Stress. CELLS, 8 (11): 1421. ISSN , 2073-4409
Full text not available from this repository. (Request a copy)Abstract
Hepatic ischemia reperfusion injury (IRI) is a major complication in liver resection and transplantation. Here, we analyzed the impact of recombinant human augmenter of liver regeneration (rALR), an anti-oxidative and anti-apoptotic protein, on the deleterious process induced by ischemia reperfusion (IR). Application of rALR reduced tissue damage (necrosis), levels of lipid peroxidation (oxidative stress) and expression of anti-oxidative genes in a mouse IRI model. Damage associated molecule pattern (DAMP) and inflammatory cytokines such as HMGB1 and TNF alpha, were not affected by rALR. Furthermore, we evaluated infiltration of inflammatory cells into liver tissue after IRI and found no change in CD3 or gamma delta TCR positive cells, or expression of IL17/IFN gamma by gamma delta TCR cells. The quantity of Gr-1 positive cells (neutrophils), and therefore, myeloperoxidase activity, was lower in rALR-treated mice. Moreover, we found under hypoxic conditions attenuated ROS levels after ALR treatment in RAW264.7 cells and in primary mouse hepatocytes. Application of rALR also led to reduced expression of chemo-attractants like CXCL1, CXCL2 and CCl2 in hepatocytes. In addition, ALR expression was increased in IR mouse livers after 3 h and in biopsies from human liver transplants with minimal signs of tissue damage. Therefore, ALR attenuates IRI through reduced neutrophil tissue infiltration mediated by lower expression of key hepatic chemokines and reduction of ROS generation.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | REACTIVE OXYGEN; HEPATIC-INJURY; IN-VITRO; HEPATOCYTES; ISCHEMIA/REPERFUSION; TRANSPLANTATION; MECHANISMS; ACTIVATOR; IMPACT; DRIVE; ischemia reperfusion; liver regeneration; chemokines; neutrophils; oxidative stress; augmenter of liver regeneration |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie Medicine > Lehrstuhl für Kinder- und Jugendmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 31 Mar 2020 05:20 |
| Last Modified: | 06 Apr 2020 06:15 |
| URI: | https://pred.uni-regensburg.de/id/eprint/25893 |
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