Astaxanthin Inhibits Interleukin‐6 Expression in Cerulein/Resistin‐Stimulated Pancreatic Acinar Cells
Min Seung Kwak, Joo Weon Lim, Hyeyoung Kim
Abstract
Acute pancreatitis is a common clinical condition with increasing the proinflammatory mediators, including interleukin‐6 (IL‐6). Obesity is a negative prognostic factor in acute pancreatitis. Obese patients with acute pancreatitis have a higher systemic inflammatory response rate. Levels of serum resistin, an adipocytokine secreted by fat tissues, increase with obesity. Cerulein, a cholecystokinin analog, induces calcium (Ca 2+ ) overload, oxidative stress, and IL‐6 expression in pancreatic acinar cells, which are hallmarks of acute pancreatitis. A recent study showed that resistin aggravates the expression of inflammatory cytokines in cerulein‐stimulated pancreatic acinar cells. We aimed to investigate whether resistin amplifies cerulein‐induced IL‐6 expression and whether astaxanthin (ASX), an antioxidant carotenoid with anti‐inflammatory properties, inhibits ceruelin/resistin‐induced IL‐6 expression in pancreatic acinar AR42J cells. We found that resistin enhanced intracellular Ca 2+ levels, NADPH oxidase activity, intracellular reactive oxygen species (ROS) production, NF‐ κ B activity, and IL‐6 expression in cerulein‐stimulated AR42J cells, which were inhibited by ASX in a dose‐dependent manner. The calcium chelator BAPTA‐AM inhibited cerulein/resistin‐induced NADPH oxidase activation and ROS production. Antioxidant N‐acetyl cysteine (NAC) and ML171, a specific NADPH oxidase 1 inhibitor, suppressed cerulein/resistin‐induced ROS production, NF‐ κ B activation, and IL‐6 expression. In conclusion, ASX inhibits IL‐6 expression, by reducing Ca 2+ overload, NADPH oxidase‐mediated ROS production, and NF‐ κ B activity in cerulein/resistin‐stimulated pancreatic acinar cells. Consumption of ASX‐rich foods could be beneficial for preventing or delaying the incidence of obesity‐associated acute pancreatitis.