{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T19:00:34Z","timestamp":1789585234967,"version":"build-2803163510"},"reference-count":33,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"published-print":{"date-parts":[[2000,7,1]]},"abstract":"<jats:p>Destruction of Kupffer cells with gadolinium chloride (GdCl<jats:sub>3<\/jats:sub>) and intestinal sterilization with antibiotics diminished ethanol-induced steatosis in the enteral ethanol feeding model. However, mechanisms of ethanol-induced fatty liver remain unclear. Accordingly, the role of Kupffer cells in ethanol-induced fat accumulation was studied. Rats were given ethanol (5 g\/kg body wt) intragastrically, and tissue triglycerides were measured enzymatically. Kupffer cells were isolated 0\u201324 h after ethanol, and PGE<jats:sub>2<\/jats:sub>production was measured by ELISA, whereas inducible cyclooxygenase (COX-2) mRNA was detected by RT-PCR. As expected, ethanol increased liver triglycerides about threefold. This increase was blunted by antibiotics, GdCl<jats:sub>3<\/jats:sub>, the dihydropyridine-type Ca<jats:sup>2+<\/jats:sup>channel blocker nimodipine, and the COX inhibitor indomethacin. Ethanol also increased PGE<jats:sub>2<\/jats:sub>production by Kupffer cells about threefold. This increase was also blunted significantly by antibiotics, nimodipine, and indomethacin. Furthermore, tissue triglycerides were increased about threefold by PGE<jats:sub>2<\/jats:sub>treatment in vivo as well as by a PGE<jats:sub>2<\/jats:sub>EP<jats:sub>2<\/jats:sub>\/EP<jats:sub>4<\/jats:sub>receptor agonist, whereas an EP<jats:sub>1<\/jats:sub>\/EP<jats:sub>3<\/jats:sub>agonist had no effect. Moreover, permeable cAMP analogs also increased triglyceride content in the liver significantly. We conclude that PGE<jats:sub>2<\/jats:sub>derived from Kupffer cells, which are activated by ethanol, interacts with prostanoid receptors on hepatocytes to increase cAMP, which causes triglyceride accumulation in the liver. 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