Hepatocyte modulation of Kupffer cell prostaglandin E2 production in vitro.
It is likely that dynamic interactions between hepatocytes and Kupffer cells contribute to the responses of these cell types both under normal conditions and during sepsis. In this study, we examined the influences of hepatocytes on the concentration of the inflammatory mediator PGE2 in Kupffer cell cultures. Evidence to suggest that cultured rat hepatocytes both metabolize PGE2 and produce a substance that promotes LPS-stimulated Kupffer cell PGE2 biosynthesis include the following: 1) PGE2 levels in Kupffer cell: hepatocyte coculture were lower than the levels in Kupffer cell cultures early after LPS stimulation; 2) 36 h after LPS, coculture PGE2 levels exceeded the levels in Kupffer cell cultures despite the demonstrated capacity for hepatocytes to metabolize PGE2; 3) a transferable, non-dialyzable, and heat-unstable factor in hepatocyte supernatant promoted PGE2 production when added to Kupffer cells with LPS or after LPS; 4) there was no increased PGE2 synthesis when the hepatocyte supernatant was added without LPS or if hepatocyte supernatant was preincubated with the Kupffer cells for 6 or 18 h before LPS administration; 5) there was an inability of the hepatocyte factor to promote PGE2 production in response to other macrophage-activating agents, including calcium ionophore A23187 or phorphol myristate acetate; and 6) there was no increased cell replication or protein synthesis in the Kupffer cell cultures following hepatocyte supernatant incubation. The increased Kupffer cell PGE2 production by the hepatocyte supernatant was not due to contamination of the hepatocyte supernatant by endotoxin or PGE2. These in vitro results raise the possibility that hepatocytes have the capacity to modulate local PGE2 levels by two distinct mechanisms. Hepatocytes can metabolize PGE2 as well as release factor(s) which promote LPS-induced PGE2 production by Kupffer cells.
Billiar
T R
TR
Department of Surgery, University of Pittsburgh, PA 15261.
Lysz
T W
TW
Curran
R D
RD
Bentz
B G
BG
Machiedo
G W
GW
Simmons
R L
RL
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002478:Cells, Cultured; D015232:Dinoprostone / Q000378:metabolism*; D004731:Endotoxins / Q000494:pharmacology; D007728:Kupffer Cells / Q000378:metabolism*; D008099:Liver / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004731:Endotoxins; D000001:Calcimycin; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate