Apelin Regulates Nuclear Factor-κB's Involvement in the Inflammatory Response of Pancreatitis

Objectives: Inflammation plays a key role in pancreatitis. Earlier studies from our laboratory showed that experimental pancreatitis activated the pancreatic apelin-APJ axis robustly inmice. Apelin signaling reduced neutrophil invasion and the activation of pancreatic nuclear factor (NF)-kappa B in mice with experimental pancreatitis. Methods: The aim of this study was to assess whether apelin-induced inhibition of pancreatic NF-kappa B activation was linked mechanistically to apelin's inhibition of pancreatic inflammatory mediator up-regulation in mice with cerulein-induced chronic pancreatitis (CP). Whether apelin's inhibitory effectswere associated with the inhibition of NF-kappa B binding to the promoter region of IL-1 beta was examined. The effects of apelin exposure on pancreatic I.B degradation/replenishment and membrane levels of phosphorylated protein kinase C were measured. Results: Results demonstrated that apelin inhibited the up-regulation of pancreatic tumor necrosis factor alpha, macrophage inflammatory protein-1 alpha/beta, and IL-1 beta expression significantly in mice with CP. Chromatin immunoprecipitation assay findings showed that apelin inhibitedNF-kappa B binding to a putative NF-kappa B binding site in the IL-1 beta promoter. Apelin exposure reduced the pancreatic membrane levels of phosphorylated protein kinase C-d and enhanced the replenishment of pancreatic I.B proteins. Conclusions: Together, these findings indicated that the inhibition of NF-kappa B activation by apelin was a mechanism behind the reduced pancreatic levels of inflammatory mediators in CP mice exposed to apelin.