Department of Food and Nutrition, BK 21 FOUR, College of Human Ecology, Yonsei University, Seoul 03722, Republic of Korea.
Mediators Inflamm. 2021 Jul 24;2021:5587297. doi: 10.1155/2021/5587297. eCollection 2021.
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) 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 levels, NADPH oxidase activity, intracellular reactive oxygen species (ROS) production, NF-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-B activation, and IL-6 expression. In conclusion, ASX inhibits IL-6 expression, by reducing Ca overload, NADPH oxidase-mediated ROS production, and NF-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.
急性胰腺炎是一种常见的临床病症，其促炎介质（包括白细胞介素-6 [IL-6]）会增加。肥胖是急性胰腺炎的一个负面预后因素。患有急性胰腺炎的肥胖患者全身炎症反应发生率更高。脂肪组织分泌的一种脂肪细胞因子——抵抗素的血清水平会随着肥胖而增加。胆囊收缩素类似物——亮抑蛋白酶原，可导致胰腺腺泡细胞内钙离子（Ca）超载、氧化应激和 IL-6 表达，这是急性胰腺炎的特征。最近的一项研究表明，抵抗素加剧了亮抑蛋白酶原刺激的胰腺腺泡细胞中炎性细胞因子的表达。我们旨在研究抵抗素是否会放大亮抑蛋白酶原诱导的 IL-6 表达，以及具有抗炎特性的抗氧化类胡萝卜素虾青素（ASX）是否会抑制胰腺腺泡 AR42J 细胞中亮抑蛋白酶原/抵抗素诱导的 IL-6 表达。我们发现，抵抗素增强了亮抑蛋白酶原刺激的 AR42J 细胞内的 Ca 水平、NADPH 氧化酶活性、细胞内活性氧（ROS）产生、NF-B 活性和 IL-6 表达，而 ASX 则以剂量依赖的方式抑制了这些变化。钙螯合剂 BAPTA-AM 抑制了亮抑蛋白酶原/抵抗素诱导的 NADPH 氧化酶激活和 ROS 产生。抗氧化剂 N-乙酰半胱氨酸（NAC）和 NADPH 氧化酶 1 特异性抑制剂 ML171 抑制了亮抑蛋白酶原/抵抗素诱导的 ROS 产生、NF-B 激活和 IL-6 表达。总之，ASX 通过减少 Ca 超载、NADPH 氧化酶介导的 ROS 产生和 NF-B 活性，抑制了亮抑蛋白酶原/抵抗素刺激的胰腺腺泡细胞中 IL-6 的表达。食用富含 ASX 的食物可能有助于预防或延缓肥胖相关急性胰腺炎的发生。
