Title data
Henkel, Janin ; Coleman, Charles Dominic ; Schraplau, Anne ; Jöhrens, Korinna ; Weiss, Thomas Siegfried ; Jonas, Wenke ; Schürmann, Annette ; Püschel, Gerhard Paul:
Augmented liver inflammation in a microsomal prostaglandin E synthase 1 (mPGES-1)-deficient diet-induced mouse NASH model.
In: Scientific Reports.
Vol. 8
(2018)
Issue 1
.
- No. 16127.
ISSN 2045-2322
DOI: https://doi.org/10.1038/s41598-018-34633-y
Project information
Project financing: |
Deutsche Forschungsgemeinschaft |
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Abstract in another language
In a subset of patients, non-alcoholic fatty liver disease (NAFLD) is complicated by cell death and inflammation resulting in non-alcoholic steatohepatitis (NASH), which may progress to fibrosis and subsequent organ failure. Apart from cytokines, prostaglandins, in particular prostaglandin E2 (PGE2), play a pivotal role during inflammatory processes. Expression of the key enzymes of PGE synthesis, cyclooxygenase 2 and microsomal PGE synthase 1 (mPGES-1), was increased in human NASH livers in comparison to controls and correlated with the NASH activity score. Both enzymes were also induced in NASH-diet-fed wild-type mice, resulting in an increase in hepatic PGE2 concentration that was completely abrogated in mPGES-1-deficient mice. PGE2 is known to inhibit TNF-α synthesis in macrophages. A strong infiltration of monocyte-derived macrophages was observed in NASH-diet-fed mice, which was accompanied with an increase in hepatic TNF-α expression. Due to the impaired PGE2 production, TNF-α expression increased much more in livers of mPGES-1-deficient mice or in the peritoneal macrophages of these mice. The increased levels of TNF-α resulted in an enhanced IL-1β production, primarily in hepatocytes, and augmented hepatocyte apoptosis. In conclusion, attenuation of PGE2 production by mPGES-1 ablation enhanced the TNF-α-triggered inflammatory response and hepatocyte apoptosis in diet-induced NASH.
Further data
Item Type: | Article in a journal |
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Refereed: | Yes |
Institutions of the University: | Faculties > Faculty of Life Sciences: Food, Nutrition and Health Faculties Faculties > Faculty of Life Sciences: Food, Nutrition and Health > Lehrstuhl Biochemie der Ernährung > Lehrstuhl Biochemie der Ernährung - Univ.-Prof. Dr. Janin Henkel-Oberländer Faculties > Faculty of Life Sciences: Food, Nutrition and Health > Lehrstuhl Biochemie der Ernährung |
Result of work at the UBT: | No |
DDC Subjects: | 500 Science 500 Science > 570 Life sciences, biology 600 Technology, medicine, applied sciences > 610 Medicine and health |
Date Deposited: | 26 Apr 2021 12:25 |
Last Modified: | 19 Oct 2022 12:57 |
URI: | https://eref.uni-bayreuth.de/id/eprint/64439 |