Production of pro- and anti-fibrotic agents by rat Kupffer cells; the effect of octreotide.
Kupffer cells may be involved in liver fibrogenesis through production of TGF-beta1. Their role in fibrinolysis is less clear. Octreotide, a synthetic analogue of somatostatin, is often used in cirrhotic patients. Its effect on Kupffer cells was studied. Isolated rat Kupffer cells were cultured in the presence of lipopolysaccharide and/or octreotide. TGF-beta1, leptin, collagenase (MMP-1), and urokinase-type plasminogen activator (uPA) were assessed in supernatants by ELISA, and MMP-2 and MMP-9 by zymography. Kupffer cells produced large amounts of MMP-1 and lipopolysaccharide induced a significant (P < 0.02) early increase. Octreotide and lipopolysaccharide caused a synergistic effect on MMP-1 secretion. By contrast, MMP-9 production stimulated by lipopolysaccharide was suppressed by octreotide. Kupffer cells produced a basal amount of uPA, significantly increased after lipopolysaccharide or octreotide incubation (P < 0.001). Large amounts of TGF-beta1 were produced in a time-dependent manner by unstimulated Kupffer cells. Lipopolysaccharide and octreotide, alone or in combination, induced a significant inhibition of this production (P < 0.01). Kupffer cells did not produce leptin, a recently identified mediator of liver fibrosis, or MMP-2. Kupffer cells may play a significant role in liver fibrinolysis. Octreotide, acting on TGF-beta1, uPA, and MMP-1 production, may be a useful agent for fibrosis resolution.
Xidakis
Costas
C
Liver Research Laboratory, Faculty of Medicine, University of Crete, 71003 Heraklion, Greece.
Ljumovic
Dushanka
D
Manousou
Pinelopi
P
Notas
George
G
Valatas
Vassilis
V
Kolios
George
G
Kouroumalis
Elias
E
D000818:Animals; D018929:Cell Culture Techniques; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D007728:Kupffer Cells / Q000187:drug effects* / Q000378:metabolism*; D020738:Leptin / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D015282:Octreotide / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
D005765:Gastrointestinal Agents; D020738:Leptin; D008070:Lipopolysaccharides; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014568:Urokinase-Type Plasminogen Activator; D020782:Matrix Metalloproteinases; D015282:Octreotide