Kupffer cell prostaglandin E2 stimulates parenchymal cell O2 consumption: alcohol and cell-cell communication.
Several studies have demonstrated that ethanol can increase hepatic O2 uptake (e.g., produce a hypermetabolic state); however, a complete explanation of this important phenomenon remains unclear. Here, the effect of conditioned media from Kupffer cells isolated from rats chronically exposed to ethanol on O2 consumption of normal parenchymal cells was studied to evaluate the possibility that cell-cell communication participates in the mechanism of the hepatic hypermetabolic state. Kupffer cells were isolated from rats fed either a liquid control diet or a diet containing ethanol. Kupffer cells were cultured for 4 h, and conditioned media were incubated with parenchymal cells isolated from untreated rats in a closed chamber with an O2 electrode. O2 consumption of parenchymal cells incubated in fresh media or conditioned media from Kupffer cells from untreated rats was approximately 30 microliters.h-1. 10(6) cells-1; however, values were increased by > 30% by conditioned media from Kupffer cells isolated from rats treated with ethanol. Indomethacin, nisoldipine, and boiling the conditioned media blocked this stimulation, suggesting the involvement of eicosanoids. Indeed, prostaglandin E2 (PGE2) added directly to parenchymal cells increased O2 consumption in a dose-dependent manner by nearly 60%. Furthermore, PGE2 levels in conditioned media from Kupffer cells isolated from ethanol-treated rats were elevated about twofold. The addition of endotoxin to cultured cells caused a similar phenomenon. Taken together, these data support the hypothesis that Kupffer cells are activated by ethanol treatment to release mediators such a PGE2, which stimulate O2 consumption in parenchymal cells, possibly by mechanisms involving bacterial endotoxin.
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Department of Pharmacology, University of North Carolina at Chapel Hill 27599-7365, USA.
Zhong
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Goto
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Thurman
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RG
D000818:Animals; D002450:Cell Communication; D017077:Culture Media, Conditioned / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology*; D004731:Endotoxins / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D007728:Kupffer Cells / Q000187:drug effects / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D017077:Culture Media, Conditioned; D004731:Endotoxins; D000431:Ethanol; D015232:Dinoprostone