Apoptosis in activated rat pancreatic stellate cells.
Proliferation and matrix synthesis by activated pancreatic stellate cells (PSC) participate in the development of chronic pancreatitis. Apoptosis of PSC may terminate this process but has not yet been studied in this particular cell type and was the aim of the present study. PSC were isolated from rat pancreas and characterized for expression of glial fibrillary acidic protein, alpha-smooth muscle actin, CD95, and tumor necrosis factor-alpha-related apoptosis-inducing ligand (TRAIL) receptors. Apoptosis was determined by TdT-UTP nick end-labeling reaction, annexin V binding, and caspase-8 activation. Both CD95L and TRAIL induced apoptosis in PSC. The apoptotic response was minor in PSC cultured for 7 days but increased markedly thereafter. Sensitization of PSC with culture duration was accompanied by increased expression of CD95 and TRAIL receptor 2 and no alterations of Flip expression or protein kinase B phosphorylation but was paralleled by the appearance of a COOH-terminal cleavage product of receptor-interacting protein. PSC apoptosis was also induced by PK-11195, a ligand of the peripheral benzodiazepine receptor. PSC apoptosis may be important in terminating the wound-healing response after pancreas injury and exhibits features distinct from apoptosis induction in hepatic stellate cells.
Department of Gastroenterology, Hepatology and Infectiology, Heinrich-Heine Universität Düsseldorf, 40225 Düsseldorf, Germany. Hanne.Klonowski-Stumpe@uni-duesseldorf.de
Hanne
H
Klonowski-Stumpe
Richard
R
Fischer
Roland
R
Reinehr
Reinhard
R
Lüthen
Dieter
D
Häussinger
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D051017:Apoptosis Regulatory Proteins; D002469:Cell Separation; D002478:Cells, Cultured; D053222:Fas Ligand Protein; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D008562:Membrane Glycoproteins / Q000494:pharmacology; D010179:Pancreas / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019014:fas Receptor / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D007546:Isoquinolines; D008562:Membrane Glycoproteins; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; D053221:TNF-Related Apoptosis-Inducing Ligand; C505644:Tnfrsf10b protein, rat; C505655:Tnfsf10 protein, rat; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; C037850:PK 11195