Fructose-1,6-Bisphosphate inhibits excess activation of Kupffer cell function induced by endotoxin.
The effect and mechanism of action of fructose-1,6-bisphosphate (FBP) on Kupffer cell activation were studied in vitro. Kupffer cell was activated by isolation procedure alone from the hepatic tissue. In cultured rat Kupffer cells stimulated by endotoxin, treatment with 5-20 mM FBP not only preserved phagocytic activity, but also inhibited secretion of cytokines (tumor necrosis factor-a and interleukin-1beta) and production of nitric oxide (NOx). Moreover, treatment with 10 mM FBP suppressed the elevation in the intracellular Ca2+ concentration on Kupffer cells stimulated by phorbol 12-myristate 13-acetate, which suggested that this effect may be one of the agents that limit the activation of Kupffer cells. The administration of FBP was effective in the prevention of endotoxin-induced hepatopathy, and we suggest that this may have useful clinical applications.
Tamaki
Takuya
T
Second Department of Surgery, Wakayama Medical University, Japan.
Nakai
Takehiro
T
Yamaue
Hiroki
H
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005635:Fructosediphosphates / Q000494:pharmacology*; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007728:Kupffer Cells / Q000187:drug effects* / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects* / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism
D005635:Fructosediphosphates; D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C029063:fructose-1,6-diphosphate; D002118:Calcium