Ghrelin inhibits IKKβ/NF-κB activation and reduces pro-inflammatory cytokine production in pancreatic acinar AR42J cells treated with cerulein

Background: Previous studies have provided conflicting results regarding whether the serum ghrelin concentration can reflect the severity of acute pancreatitis(AP). The present study examined the correlation between the serum ghrelin concentration and AP severity in animal models and investigated whether altered ghrelin expression in pancreatic acinar cells influences IKK β/NF-κ B signaling and pro-inflammatory cytokine production. Methods: Mild or severe AP was induced in rats by intraperitoneal injection of cerulein or retrograde cholangiopancreatic duct injection of sodium taurocholate, respectively. After successful model induction, serum ghrelin, tumor necrosis factor-α(TNF-α), and interleukin-6(IL-6) concentrations were determined by enzyme-linked immunosorbent assay, and IKK β/NF-κ B activation was assessed by immunohistochemistry. Subsequently, stable overexpression or knockdown of ghrelin in AR42 J cells was achieved by lentiviral transfection. After transfected cells and control cells were treated with cerulein for 24 h, the TNF-αand IL-1 β levels in the supernatants were determined by enzyme-linked immunosorbent assay, and the expression levels of p-p65, IKK β, and p-IKK β were detected by Western blotting. Results: In rat AP models, AP severity was correlated with increased IKK β/NF-κ B activation, proinflammatory cytokine production, and ghrelin secretion. The levels of pro-inflammatory cytokines TNF-αand IL-1 β as well as IKK β/NF-κ B signaling activity were increased upon knockdown of ghrelin in the AP acinar cell model and decreased with ghrelin overexpression. Conclusions: Serum ghrelin is related to the severity of AP. Ghrelin may play a protective role in the pathogenesis of AP by inhibiting the pro-inflammatory cytokines and the activation of the IKK β/NF-κ B signaling pathway.