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 (Ca2+) 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 Ca2+ levels, NADPH oxidase activity, intracellular reactive oxygen species (ROS) production, NF-κB 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-κB activation, and IL-6 expression. In conclusion, ASX inhibits IL-6 expression, by reducing Ca2+ overload, NADPH oxidase-mediated ROS production, and NF-κB 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.
Highlights
Acute pancreatitis is a common inflammatory disorder, the incidence of which has been increasing over recent years [1]
Rao and Kunte [6] measured serum IL-6, IL-8, IL-10, and C-reactive protein (CRP) levels within 24 h of admission in forty patients of clinically predicted severe acute pancreatitis (SAP). They found that IL‐6 ≥ 28:90 pg/mL had a sensitivity of 62.86%, specificity of 80%, and positive predictive value (PPV) of 95.65%, demonstrating that IL-6 is the best among the tested biomarkers for predicting the progression to severe pancreatitis
We investigated whether ASX inhibits cerulein/resistin-induced IL-6 expression by suppressing Ca2+ overload and NADPH oxidase-mediated reactive oxygen species (ROS) production in AR42J cells
Summary
Acute pancreatitis is a common inflammatory disorder, the incidence of which has been increasing over recent years [1]. Acinar cell injury early in acute pancreatitis leads to a local inflammatory reaction with increasing the proinflammatory mediators [3]. Rao and Kunte [6] measured serum IL-6, IL-8, IL-10, and C-reactive protein (CRP) levels within 24 h of admission in forty patients of clinically predicted severe acute pancreatitis (SAP). They found that IL‐6 ≥ 28:90 pg/mL had a sensitivity of 62.86%, specificity of 80%, and positive predictive value (PPV) of 95.65%, demonstrating that IL-6 is the best among the tested biomarkers for predicting the progression to severe pancreatitis. There was a significant correlation between IL-6 at 5 h and both
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