α-Lipoic Acid Inhibits IL-6 Expression by Upregulating PPAR-γ-Mediated Expression of Antioxidants in Cerulein/Resistin-Stimulated Pancreatic Acinar Cells

Abstract

ObjectivesOxidative stress is regarded as a major pathogenic factor in acute pancreatitis. Obesity is thought to be a negative prognostic factor in acute pancreatitis. Levels of serum resistin, an adipocytokine secreted by fat tissues, increase with obesity. Recent study showed that resistin aggravates the expression of inflammatory cytokines such as interleukine-6 (IL-6) and production of reactive oxygen species (ROS) in pancreatic acinar cells stimulated with cerulein, a cholecystokinin analogue, as an in vitro acute pancreatitis model. Peroxisome proliferator-activated receptor (PPAR)-γ increases expression of antioxidant enzymes such as catalase and heme oxygenase-1 (HO-1). α-Lipoic acid is a powerful antioxidant and anti-inflammatory nutrient. The present study was purposed to investigate whether α-lipoic acid inhibits IL-6 expression in resistin/cerulein-stimulated pancreatic acinar cells and to determine whether it reduces ROS in AR42J cells by upregulating PPAR-γ-mediated expression of HO-1 and catalase in pancreatic acinar cells. MethodsRat pancreatic acinar cell line, AR42J cells, were stimulated with resistin (2 ng/ml) and cerulean (10–8 M), in the presence or absence of α-lipoic acid. mRNA expression of IL-6 was determined by real-time PCR analysis. ROS levels were measured using DCF-DA fluorescence. Expression of PPAR-γ, HO-1, and catalase were determined by Western blotting. Resultsα-Lipoic acid significantly decreased IL-6 mRNA expression and ROS production in resistin/cerulein-stimulated AR42J cells. α-Lipoic acid also increased expression of PPAR-γ, HO-1 and catalase. Inhibitory effect of α-lipoic acid on resistin/cerulein–induced IL-6 expression was suppressed by addition of a specific PPAR-γ inhibitor GW9662. GW9662 reversed the effect of α-lipoic acid on expression of HO-1 and catalase in AR42J cells. Conclusionsα-Lipoic acid suppresses cerulein/resistin-induced IL-6 expression and ROS production through PPAR-γ-mediated expression of HO-1 and catalase in pancreatic acinar cells. Funding SourcesThis study was supported by a Brain Korea 21 FOUR Project, Yonsei University, Seoul, Republic of Korea.