Digestive Diseases and Sciences

, Volume 50, Issue 5, pp 935–941 | Cite as

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

  • Costas Xidakis
  • Dushanka Ljumovic
  • Pinelopi Manousou
  • George Notas
  • Vassilis Valatas
  • George Kolios
  • Elias Kouroumalis
Article

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.

Key Words

Kupffer cells fibrosis lipopolysaccharide octreotide cytokines matrix metalloproteases 

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Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • Costas Xidakis
    • 1
  • Dushanka Ljumovic
    • 1
  • Pinelopi Manousou
    • 1
  • George Notas
    • 1
  • Vassilis Valatas
    • 1
  • George Kolios
    • 1
    • 2
  • Elias Kouroumalis
    • 1
    • 2
    • 3
  1. 1.Liver Research LaboratoryUniversity of CreteHeraklionGreece
  2. 2.Department of Gastroenterology, Faculty of MedicineUniversity of CreteHeraklionGreece
  3. 3.Department of GastroenterologyUniversity HospitalHeraklionGreece

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