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Pancreatic elastase induces liver injury by activating cytokine production within Kupffer cells via nuclear factor-Kappa B.
- Source :
-
Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract [J Gastrointest Surg] 2002 May-Jun; Vol. 6 (3), pp. 474-80. - Publication Year :
- 2002
-
Abstract
- Liver injury is a manifestation of the systemic inflammatory response during acute pancreatitis. We have demonstrated that elastase induces macrophage tumor necrosis factor (TNF) production in distant organs, thus mimicking pancreatitis-associated organ injury. The aim of this study was to determine the mechanism by which elastase induces hepatic cytokine production. Rat livers (n = 40) were perfused with elastase +/- gadolinium (Gd) to inhibit Kupffer cells. Liver parenchymal enzymes and TNF were measured in the effluent. In vitro, rat hepatocytes or Kupffer cells were treated with elastase (1 U/ml) +/- Gd (0.5 mg/ml) or pyrrolidine dithiocarbamate (PDTC; 0.5 mg/ml). TNF protein, TNF messenger RNA, and NF-kappa B activation were determined. In vivo, Gd blunted the elastase-induced TNF production and decreased AST, ALT, LDH, and nonviable cells (propidium iodide) (P < or= 0.03 vs. elastase). In vitro, elastase induced TNF production from Kupffer cells (P < 0.001 vs. control) but not from hepatocytes. Gd or PDTC significantly attenuated the elastase-induced TNF production (P < 0.001). Elastase-induced overexpression of TNF messengerRNA and activation of NF-kappa B was attenuated by Gd. Pancreatic elastase induces a pattern of liver injury similar to that seen during acute pancreatitis by activating cytokine production and gene expression within Kupffer cells via NF-kappa B. Gd exhibits a protective effect against elastase-induced liver injury by inhibiting activation of NF-kappa B.
- Subjects :
- Animals
Cells, Cultured
Electrophoresis, Agar Gel
Electrophoretic Mobility Shift Assay
Hepatocytes metabolism
In Vitro Techniques
Male
Random Allocation
Rats
Rats, Sprague-Dawley
Tumor Necrosis Factor-alpha metabolism
Cytokines metabolism
Kupffer Cells metabolism
Liver metabolism
NF-kappa B physiology
Pancreatic Elastase physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1091-255X
- Volume :
- 6
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract
- Publication Type :
- Academic Journal
- Accession number :
- 12023002
- Full Text :
- https://doi.org/10.1016/s1091-255x(01)00071-3