Henkel, Janin and Coleman, Charles Dominic and Schraplau, Anne and Joehrens, Korinna and Weiss, Thomas Siegfried and Jonas, Wenke and Schuermann, Annette and Pueschel, Gerhard Paul (2018) Augmented liver inflammation in a microsomal prostaglandin E synthase 1 (mPGES-1)-deficient diet-induced mouse NASH model. SCIENTIFIC REPORTS, 8: 16127. ISSN 2045-2322,
Full text not available from this repository. (Request a copy)Abstract
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 E-2 (PGE(2)), play a pivotal role during inflammatory processes. Expression of the key enzymes of PGE(2) 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 PGE(2) concentration that was completely abrogated in mPGES-1-deficient mice. PGE(2) is known to inhibit TNF-alpha 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-alpha expression. Due to the impaired PGE(2) production, TNF-alpha expression increased much more in livers of mPGES-1-deficient mice or in the peritoneal macrophages of these mice. The increased levels of TNF-alpha resulted in an enhanced IL-1 beta production, primarily in hepatocytes, and augmented hepatocyte apoptosis. In conclusion, attenuation of PGE(2) production by mPGES-1 ablation enhanced the TNF-alpha-triggered inflammatory response and hepatocyte apoptosis in diet-induced NASH.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SUPPRESS VLDL SECRETION; MICE LACKING; NONALCOHOLIC STEATOHEPATITIS; INSULIN-RESISTANCE; KUPFFER CELLS; E-2; ACCUMULATION; HEPATOCYTES; INHIBITION; EXPRESSION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Kinder- und Jugendmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 04 Dec 2019 10:21 |
| Last Modified: | 04 Dec 2019 10:21 |
| URI: | https://pred.uni-regensburg.de/id/eprint/13664 |
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