TY  - JOUR
A1  - Queck, Alexander David Roger
A1  - Fink, Annika F.
A1  - Sirait-Fischer, Evelyn Nicole Joy
A1  - Rüschenbaum, Sabrina
A1  - Thomas, Dominique Jeanette
A1  - Snodgrass, Ryan G.
A1  - Geisslinger, Gerd
A1  - Baba, Hideo Andreas
A1  - Trebicka, Jonel
A1  - Zeuzem, Stefan
A1  - Weigert, Andreas
A1  - Lange, Christian
A1  - Brüne, Bernhard
T1  - Alox12/15 deficiency exacerbates, while Lipoxin A4 ameliorates hepatic inflammation in murine alcoholic hepatitis
T2  - Frontiers in immunology
N2  - Alcoholism is one of the leading and increasingly prevalent reasons of liver associated morbidity and mortality worldwide. Alcoholic hepatitis (AH) constitutes a severe disease with currently no satisfying treatment options. Lipoxin A4 (LXA4), a 15-lipoxygenase (ALOX15)-dependent lipid mediator involved in resolution of inflammation, showed promising pre-clinical results in the therapy of several inflammatory diseases. Since inflammation is a main driver of disease progression in alcoholic hepatitis, we investigated the impact of endogenous ALOX15-dependent lipid mediators and exogenously applied LXA4 on AH development. A mouse model for alcoholic steatohepatitis (NIAAA model) was tested in Alox12/15+/+ and Alox12/15−/− mice, with or without supplementation of LXA4. Absence of Alox12/15 aggravated parameters of liver disease, increased hepatic immune cell infiltration in AH, and elevated systemic neutrophils as a marker for systemic inflammation. Interestingly, i.p. injections of LXA4 significantly lowered transaminase levels only in Alox12/15−/− mice and reduced hepatic immune cell infiltration as well as systemic inflammatory cytokine expression in both genotypes, even though steatosis progressed. Thus, while LXA4 injection attenuated selected parameters of disease progression in Alox12/15−/− mice, its beneficial impact on immunity was also apparent in Alox12/15+/+ mice. In conclusion, pro-resolving lipid mediators may be beneficial to reduce inflammation in alcoholic hepatitis.
KW  - alcoholic hepatitis
KW  - arachidonate 12/15-lipoxygenase (Alox12/15)
KW  - specialized pro-resolving lipid mediators (SPMs)
KW  - resolution of inflammation
KW  - lipoxin A4
Y1  - 2020
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/55463
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-554639
SN  - 1664-3224
N1  - © 2020 Queck, Fink, Sirait-Fischer, Rüschenbaum, Thomas, Snodgrass, Geisslinger, Baba, Trebicka, Zeuzem, Weigert, Lange and Brüne. This is an openaccess article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
VL  - 11
IS  - art. 1447
SP  - 1
EP  - 13
PB  - Frontiers
CY  - Lausanne
ER  -