title: Signal transduction of cerulein-induced cytokine expression and apoptosis in pancreatic acinar cells.
abstract: The signaling pathways mediating cytokine production and apoptosis in pancreatic acinar cells have not been fully understood. We investigated the signal transduction of cerulein-induced cytokine IL-6 expression and apoptosis in pancreatic acinar AR42J cells. The wild-type cells and the cells transfected with mutant genes for signaling molecules (such as transcription factor NF-kappaB and AP-1) and ras, the upstream signal for mitogen-activated protein kinase (MAPK), were used. IL-6 level was determined in the medium by enzyme-linked immunosorbent assay (ELISA). Apoptosis was determined by viable cell counts and DNA fragmentation. Wild-type cells and transfected cells with control vector (pcDNA), IkappaB mutant gene (IkappaB mt), H-ras mutant gene (Ras N17), or c-jun dominant negative gene (TAM-67) were treated with cerulein for 24 hours. As a result, cerulein induced IL-6 expression time-dependently at 10(-8) M, and apoptosis dose-dependently at 24 h in the wild-type cells. Cerulein-induced IL-6 expression (at 10(-8) M) and apoptosis (at 10(-7) M) were inhibited in the transfected cells with mutant gene (IkappaB mt, Ras N17, TAM-67) as compared to pcDNA cells and the wild-type cells. In conclusion, cerulein induces cytokine expression and apoptotic cell death, which may be regulated by NF-kappaB, AP-1, and possibly MAPK in pancreatic acinar cells.
authors.affiliation: Department of Pharmacology, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Korea.
authors.forename: Jangwon
authors.initials: J
authors.lastname: Lee
authors.forename: Jeonghun
authors.initials: J
authors.lastname: Seo
authors.forename: Hyeyoung
authors.initials: H
authors.lastname: Kim
authors.forename: Jae Bock
authors.initials: JB
authors.lastname: Chung
authors.forename: Kyung Hwan
authors.initials: KH
authors.lastname: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology; D002108:Ceruletide / Q000494:pharmacology*; D016207:Cytokines / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects; D011905:Genes, ras; D010179:Pancreas / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014162:Transfection
chemical_list: D016207:Cytokines; D002108:Ceruletide