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.

中文翻译：

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虾青素抑制 Cerulein/Resistin 刺激的胰腺腺泡细胞中 IL-6 的表达

急性胰腺炎是一种常见的临床疾病，促炎介质包括白细胞介素 6 (IL-6) 增加。肥胖是急性胰腺炎的不良预后因素。肥胖的急性胰腺炎患者全身炎症反应率较高。血清抵抗素（一种由脂肪组织分泌的脂肪细胞因子）的水平会随着肥胖而增加。Cerulein 是一种胆囊收缩素类似物，可诱导钙（Ca ²⁺) 超负荷、氧化应激和胰腺腺泡细胞中的 IL-6 表达，这是急性胰腺炎的标志。最近的一项研究表明，抵抗素会加重雨蛙素刺激的胰腺腺泡细胞中炎性细胞因子的表达。我们的目的是研究抵抗素是否会放大 cerulein 诱导的 IL-6 表达，以及虾青素 (ASX) 是一种具有抗炎特性的抗氧化类胡萝卜素，是否抑制 cerulein/resistin 诱导的胰腺腺泡 AR42J 细胞中的 IL-6 表达。我们发现抵抗素增强细胞内 Ca ²⁺水平、NADPH 氧化酶活性、细胞内活性氧 (ROS) 产生、NF- κB 活性和在 cerulein 刺激的 AR42J 细胞中的 IL-6 表达，它们被 ASX 以剂量依赖性方式抑制。钙螯合剂 BAPTA-AM 抑制 cerulein/resistin 诱导的 NADPH 氧化酶活化和 ROS 产生。抗氧化剂 N-乙酰半胱氨酸 (NAC) 和 ML171（一种特定的 NADPH 氧化酶 1 抑制剂）抑制了 cerulein/resistin 诱导的 ROS 产生、NF- κ B 活化和 IL-6 表达。总之，ASX 通过减少 Ca ²⁺超载、NADPH 氧化酶介导的 ROS 产生和雨蛙素/抵抗素刺激的胰腺腺泡细胞中的NF- κ B 活性来抑制 IL-6 表达。食用富含 ASX 的食物可能有利于预防或延缓肥胖相关的急性胰腺炎的发生。