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Production of Pro- and Anti-fibrotic Agents by Rat Kupffer Cells; The Effect of Octreotide

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Abstract

Kupffer cells may be involved in liver fibrogenesis through production of TGF-β1. 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-β1, 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-β1 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-β1, uPA, and MMP-1 production, may be a useful agent for fibrosis resolution.

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Authors and Affiliations

  1. Liver Research Laboratory, University of Crete, 71003, Heraklion, Greece

    Costas Xidakis BSc, PhD, Dushanka Ljumovic BSc, Pinelopi Manousou MD, George Notas MD, Vassilis Valatas MD, PhD, George Kolios MD, PhD & Elias Kouroumalis MD, PhD

  2. Department of Gastroenterology, Faculty of Medicine, University of Crete, 71003, Heraklion, Greece

    George Kolios MD, PhD & Elias Kouroumalis MD, PhD

  3. Department of Gastroenterology, University Hospital, P.O. Box 1352, 71110, Heraklion, Crete, Greece

    Elias Kouroumalis MD, PhD

Authors
  1. Costas Xidakis BSc, PhD
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  2. Dushanka Ljumovic BSc
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  3. Pinelopi Manousou MD
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  4. George Notas MD
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  5. Vassilis Valatas MD, PhD
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  6. George Kolios MD, PhD
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  7. Elias Kouroumalis MD, PhD
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Correspondence to Elias Kouroumalis MD, PhD.

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Xidakis, C., Ljumovic, D., Manousou, P. et al. Production of Pro- and Anti-fibrotic Agents by Rat Kupffer Cells; The Effect of Octreotide. Dig Dis Sci 50, 935–941 (2005). https://doi.org/10.1007/s10620-005-2668-8

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  • DOI: https://doi.org/10.1007/s10620-005-2668-8

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