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Augmented liver inflammation in a microsomal prostaglandin E synthase 1 (mPGES-1)-deficient diet-induced mouse NASH model

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 (31 October 2018) Issue 1 . - Art.Nr. 16127.
ISSN 2045-2322
DOI: https://doi.org/10.1038/s41598-018-34633-y

Project information

Project financing: Deutsche Forschungsgemeinschaft

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
Refereed: Yes
Institutions of the University: Faculties > Faculty of Life Sciences: Food, Nutrition and Health
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: 27 Apr 2021 11:41
URI: https://eref.uni-bayreuth.de/id/eprint/64439