CARD9 gene silencing with siRNA protects rats against severe acute pancreatitis: CARD9-dependent NF-κB and P38MAPKs pathway.

ABSTRACT

We previously reported the up-regulation of caspase recruitment domain 9 (CARD9) expressions in severe acute pancreatitis (SAP) patients, but little is known about its regulation. In this study, small interfering RNA (siRNA) was used to reduce the levels of CARD9 expression in sodium taurocholate-stimulated SAP rats. CARD9 was overexpressed in SAP rats, which correlated with the severity of pancreatitis. When compared to the untreated group, the cohort that received the siRNA treatment demonstrated a significant reduction in pancreatic injury, neutrophil infiltration, myeloperoxidase activity and pro-inflammatory cytokines. Furthermore, siRNAs showed that the reduction of CARD9 in SAP rats down-regulated the expression of NF-κBp65 and P38MAPK which are involved in the transcription and release of a wide variety of inflammatory cytokines. These findings provide evidence that CARD9 is up-regulated in SAP rats and acts as a potential therapeutic target for the treatment thereof. Blocking the activation of NF-κB and P38MAPK via siRNA-mediated gene knock-down of CARD9 appears to reduce the inflammatory response in pancreatic tissue.