ArticlePloS one2017
15-hydroxyprostaglandin dehydrogenase (15-PGDH) prevents lipopolysaccharide (LPS)-induced acute liver injury.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 32 citations in OpenAlex.
- Early-Life Vitamin A Deficiency Induces Tissue-Specific Oxylipin Remodeling and Hepatic Inflammation.Nutrients · 2026Article
- Advancements in Understanding the Role of Oxylipins in Liver Injury and Liver Failure.Journal of clinical and translational hepatology · 2026Review
- Article
- HPGD: An Intermediate Player in Microglial Polarization and Multiple Sclerosis Regulated by Nr4a1.Molecular neurobiology · 2025Article
- Inhibition of 15-hydroxyprostaglandin dehydrogenase protects neurons from ferroptosis in ischemic stroke.MedComm · 2024Article
- 15-keto-PGEiScience · 2023Article
- Bioinformatics-led discovery of liver-specific genes and macrophage infiltration in acute liver injury.Frontiers in immunology · 2023Article
- Eicosanoids and other oxylipins in liver injury, inflammation and liver cancer development.Frontiers in physiology · 2023Review
- Ginsenoside Rb1 Promotes Hepatic Glycogen Synthesis to Ameliorate T2DM Through 15-PGDH/PGEDiabetes, metabolic syndrome and obesity : targets and therapy · 2023Article
- The complex role of prostaglandin EAmerican journal of physiology. Regulatory, integrative and comparative physiology · 2021Review
- Overview on the Discovery and Development of Anti-Inflammatory Drugs: Should the Focus Be on Synthesis or Degradation of PGEJournal of inflammation research · 2021Review
- Role of prostaglandin E2 in tissue repair and regeneration.Theranostics · 2021Review
- Article
- 15-Keto prostaglandin ERedox biology · 2019Article
- Hypothalamic POMC expression is required for peripheral insulin action on hepatic gluconeogenesis through regulating STAT3 in sepsis rats.Journal of cellular and molecular medicine · 2018Article
- Article
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
The NAD+-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH) catalyzes the oxidation of the 15(S)-hydroxyl group of prostaglandin E2 (PGE2), converting the pro-inflammatory PGE2 to the anti-inflammatory 15-keto-PGE2 (an endogenous ligand for peroxisome proliferator-activated receptor-gamma [PPAR-γ]). To evaluate the significance of 15-PGDH/15-keto-PGE2 cascade in liver inflammation and tissue injury, we generated transgenic mice with targeted expression of 15-PGDH in the liver (15-PGDH Tg) and the animals were subjected to lipopolysaccharide (LPS)/Galactosamine (GalN)-induced acute liver inflammation and injury. Compared to the wild type mice, the 15-PGDH Tg mice showed lower levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), less liver tissue damage, less hepatic apoptosis/necrosis, less macrophage activation, and lower inflammatory cytokine production. In cultured Kupffer cells, treatment with 15-keto-PGE2 or the conditioned medium (CM) from 15-PGDH Tg hepatocyes inhibited LPS-induced cytokine production, in vitro. Both 15-keto-PGE2 and the CM from15-PGDH Tg hepatocyes also up-regulated the expression of PPAR-γ downstream genes in Kupffer cells. In cultured hepatocytes, 15-keto-PGE2 treatment or 15-PGDH overexpression did not influence TNF-α-induced hepatocyte apoptosis. These findings suggest that 15-PGDH protects against LPS/GalN-induced liver injury and the effect is mediated via 15-keto-PGE2, which activates PPAR-γ in Kupffer cells and thus inhibits their ability to produce inflammatory cytokines. Accordingly, we observed that the PPAR-γ antagonist, GW9662, reversed the effect of 15-keto-PGE2 in Kupffer cell in vitro and restored the susceptibility of 15-PGDH Tg mice to LPS/GalN-induced acute liver injury in vivo. Collectively, our findings suggest that 15-PGDH-derived 15-keto-PGE2 from hepatocytes is able to activate PPAR-γ and inhibit inflammatory cytokine production in Kupffer cells and that this paracrine mechanism negatively regulates LPS-induced necro-inflammatory response in the liver. Therefore, induction of 15-PGDH expression or utilization of 15-keto-PGE2 analogue may have therapeutic benefits for the treatment of endotoxin-associated liver inflammation/injury.
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