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-κB 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), IκB mutant gene (IκB 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 (IκB 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-κB, AP-1, and possibly MAPK in pancreatic acinar cells.
All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)
- History and Philosophy of Science