α‑lipoic acid inhibits cerulein/resistin‑induced expression of interleukin‑6 by activating peroxisome proliferator‑activated receptor‑γ in pancreatic acinar cells.

Abstract

Cerulein-induced pancreatitis resembles human acute pancreatitis in terms of pathological events, such as enzymatic activation and inflammatory cell infiltration in the pancreas. Cerulein is a cholecystokinin analog that increases levels of reactive oxygen species (ROS) and interleukin-6 (IL-6) expression level in pancreatic acinar cells. Serum levels of resistin, which is secreted from adipocytes, are reportedly higher in patients with acute pancreatitis than in healthy individuals. Previously, it was shown that the adipokine resistin can aggravate the cerulein-induced increase in ROS levels and IL-6 expression level in pancreatic acinar cells. Peroxisome proliferator-activated receptor-gamma (PPAR-γ) is a key regulator of the transcription and expression of antioxidant enzymes, including heme oxygenase 1 (HO-1) and catalase. α-lipoic acid, a naturally occurring dithiol antioxidant, can prevent cerulein-induced pancreatic damage in rats. In the present study, it was aimed to investigate whether α-lipoic acid can attenuate the cerulein/resistin-induced increase in IL-6 expression and ROS levels via PPAR-γ activation in pancreatic acinar AR42J cells. The anti-inflammatory mechanism of α-lipoic acid was determined using reverse transcription-quantitative PCR, western blot analysis, enzyme-linked immunosorbent assay, immunofluoresc2ence staining and fluorometry. Treatment with cerulein and resistin increased ROS levels and IL-6 expression level, which were inhibited by α-lipoic acid in pancreatic acinar cells. α-lipoic acid increased the nuclear translocation and expression level of PPAR-γ and the expression levels of its target genes: HO-1 and catalase. The PPAR-γ antagonist GW9662 and HO-1 inhibitor zinc protoporphyrin reversed the inhibitory effect of α-lipoic acid on cerulein/resistin-induced increase in ROS and IL-6 levels. In conclusion, α-lipoic acid inhibits the cerulein/resistin-induced increase in ROS production and IL-6 expression levels by activating PPAR-γ and inducing the expression of HO-1 and catalase in pancreatic acinar cells.