Effect of Prostaglandin E Receptor Subtype EP4 Selective Agonist on the Secretion of Tumor Necrosis Factor-?? by Macrophages in Acute Ethanol-Loaded Rats
- 1 August 2004
- journal article
- research article
- Published by Wiley in Alcohol, Clinical and Experimental Research
- Vol. 28 (Supplement) , 123S-128S
- https://doi.org/10.1097/01.alc.0000133541.13670.58
Abstract
It is suggested that endotoxin and proinflammatory cytokines play an important role in the development and progression of alcoholic liver disease. Recently, a prostaglandin receptor subtype EP4 agonist with cytoprotective effect has been developed. We examined the efficacy of an EP4 agonist ONO-AE1-437 on tumor necrosis factor-alpha (TNF-alpha) secretion of Kupffer cells, splenic macrophages, and alveolar macrophages in acute ethanol-loaded rats. Kupffer cells, splenic macrophages, and alveolar macrophages were isolated from control and acute ethanol-loaded rats (5 mg/g body weight of ethanol, intraperitoneally). After the preculture in the medium that containing 0, 0.1, 1, 10, or 100 nmol/liter of ONO-AE1-437, TNF-alpha secretion of these cells stimulated by 100 ng/ml of endotoxin was determined for 3 hr. The amount of TNF-alpha secreted from alveolar macrophages was largest in both the control and the acute ethanol-loaded rats. Acute ethanol load enhances TNF-alpha secretion of splenic macrophages. The addition of ONO-AE1-437 significantly inhibited TNF-alpha secretion of Kupffer cells and splenic macrophages in both the control and the acute ethanol-loaded rats. Alveolar macrophages were less affected. An EP4 agonist ONO-AE1-437 suppresses excess TNF-alpha secretion from macrophages and seems promising for future trial in patients with severe alcoholic hepatitis.Keywords
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