αlipoic acid inhibits cerulein/resistin induced expression of interleukin 6 by activating peroxisome proliferator activated receptorγ in pancreatic acinar cells

ceruleininduced 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 interleukin6 (il6) 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 indi viduals. Previously, it was shown that the adipokine resistin can aggravate the ceruleininduced increase in roS levels and il6 expression level in pancreatic acinar cells. Peroxisome proliferatoractivated receptorgamma (PParγ) is a key regulator of the transcription and expression of antioxidant enzymes, including heme oxygenase 1 (Ho1) and catalase. αlipoic acid, a naturally occurring dithiol antioxidant, can prevent ceruleininduced pancreatic damage in rats. in the present study, it was aimed to investigate whether αlipoic acid can attenuate the cerulein/resistininduced increase in il6 expression and roS levels via PParγ activation in pancre atic acinar AR42J cells. The antiinflammatory mechanism of αlipoic acid was determined using reverse transcrip tionquantitative Pcr, western blot analysis, enzymelinked immunosorbent assay, immunofluoresc2ence staining and fluorometry. Treatment with cerulein and resistin increased roS levels and il6 expression level, which were inhibited by αlipoic acid in pancreatic acinar cells. αlipoic acid increased the nuclear translocation and expression level of PParγ and the expression levels of its target genes: Ho1 and catalase. The PParγ antagonist GW9662 and Ho1 inhibitor zinc protoporphyrin reversed the inhibitory effect of αlipoic acid on cerulein/resistininduced increase in roS and il6 levels. in conclusion, αlipoic acid inhibits the cerulein/resistininduced increase in roS production and il6 expression levels by activating PParγ and inducing the expression of Ho1 and catalase in pancreatic acinar cells.