Trypsinogen activation peptide induces HMGB1 release from rat pancreatic acinar cells

Abstract

AbstractBackgroundThe development of acute pancreatitis (AP) is associated with intracellular events in pancreatic cells, as well as with early and late inflammatory responses; however, their underlying mechanisms remain unclear. This study investigated trypsinogen activation peptide (TAP)-induced release of high mobility group box-l (HMGB1) from pancreatic acinar cells and how ethyl pyruvate (EP) affects this release.MethodologyPancreatic acinar cells from Sprague Dawley rats were divided into control, TAP (administered TAP), and EP (administered TAP and EP) groups. Cells were collected at 3, 6, 12, and 24 hours after TAP administration to detect HMGB1 mRNA and protein levels using quantitative PCR (qPCR) and Western blotting, respectively.ResultsThe TAP and EP groups exhibited higher levels of HMGB1 mRNA and protein expression (P<0.05) than the control group. The HMGB1 mRNA and protein expression levels also increased with prolonged TAP activity (P<0.05)–especially at 12 and 24 hours (P<0.01)–and showed positive correlations with TAP activity duration (3, 6, 12, and 24 hours) (r=0.971, P<0.01; r=0.966, P<0.01, respectively).ConclusionTAP induces HMGB1 release from pancreatic acinar cells. A positive temporal link exists between early TAP activity and late HMGB1 expression in AP, and EP inhibits HMGB1 release.