Lutein Inhibits IL-6 Expression via PPARγ-Mediated SOCS3 Expression in Cerulein-Stimulated Pancreatic Acinar Cells

Abstract

Abstract Objectives Cerulein pancreatitis is the best model of human edematous pancreatitis. Our previous studies showed that cerulein induced interleukin-6 (IL-6) expression through janus kinase (JAK)2/signal transducer and activator of transcription (STAT)3 signaling pathway. SOCS3 functions by inhibiting the catalytic activity of JAKs that initiate signaling within the cells. Peroxisome proliferator activated receptor-gamma (PPAR-γ) ligands, 15d-PGJ2 and troglitazone, have been known to induce suppressor of cytokine signaling (SOCS) 3 expression and inhibited JAK2/STAT3 activation in pancreatic acinar cells. Lutein is a carotenoid with reported anti-inflammatory properties. The present study was undertaken to investigate the inhibitory effect and mechanism of lutein on cerulein-induced IL-6 expression by determining expression and activation of PPAR-γ and SOCS3 in pancreatic acinar cells. Methods Rat Pancreatic acinar cells (AR42J cell line) were used. The cells were treated with lutein in the presence or absence of the PPARγ antagonist GW9662, and then stimulated with cerulein. Expression of IL-6 was assessed by real-time PCR analysis. Western blot analysis was performed to determine levels of phosphorylated JAK2/STAT3 and SOCS 3, and nuclear translocation of PPAR. Results Lutein increased expression and nuclear translocation of PPARγ, and expression of SOCS 3 in AR42J cells. Cerulein-induced IL-6 expression, and phosphorylation of JAK2 and STAT3 were inhibited by lutein. GW9662 inhibited lutein-induced expression of SOCS 3. In addition, GW9662 suppressed inhibitory effects of lutein on cerulein-induced IL-6 expression and JAK2/STAT3 activation in AR42J cells. Conclusions Lutein induces PPARγ activation and SOCS 3 expression, which inhibits JAK2/STAT3 activation and IL-6 expression in cerulein-stimulated pancreatic acinar cells. Funding Sources This study was supported by Brain Korea 21 FOUR Project, Yonsei University, Seoul, Republic of Korea.