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Docosahexaenoic Acid Inhibits Cerulein‐Induced Cytokine Expression by Activating Peroxisome Proliferator‐Activated Receptor γ in Pancreatic Acinar Cells
Author(s) -
Song Eun Ah,
Lim Joo Weon,
Kim Hyeyoung
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.269.6
Subject(s) - peroxisome proliferator activated receptor , cytokine , oxidative stress , chemistry , stat protein , reactive oxygen species , medicine , endocrinology , stat3 , apocynin , nadph oxidase , receptor , signal transduction , biology , biochemistry
Oxidative stress is regarded as a major pathogenic factor in acute pancreatitis. Cerulein pancreatitis is similar to human edematous pancreatitis involving dysregulation of digestive enzyme production, cytoplasmic vacuolization, and increased cytokine production. Previously, we showed that cerulein activates NADPH oxidase to produce reactive oxygens species (ROS). ROS mediate Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway and cytokine expression in pancreatic acinar cells. And agonists of peroxisome proliferator‐activated receptor γ (PPARγ) inhibit cerulein‐induced cytokine expression by regulating JAK2/STAT3 in pancreatic acinar cells. Docosahexaenoic acid (DHA) exerts anti‐inflammatory and anti‐oxidant effect. Recently, DHA has been known to activate PPARγ in the cells. PPARs are ligand‐activated transcription factors belonging to nuclear receptor superfamily. PPARγ ligands show anti‐inflammatory activities in various cells by inhibiting the expression of pro‐inflammatory cytokines. PPARγ agonists protect the cells against oxidative stress‐mediated inflammation through reducing ROS levels by inducing antioxidant enzymes such as catalase and GSH peroxidase. The present study is purposed to investigate whether DHA inhibits cerulein‐induced cytokine expression by activating PPARγ and inhibiting JAK2/STAT3 signaling in pancreatic acinar AR42J cells. The cells were pre‐treated with DHA for 2h, and then stimulated with cerulein (10 −8 M). In other sets of experiments, the cells were treated with PPARγ agonists (Troglitazone, 15‐Deoxy‐ Δ 12,14 ‐prostaglandin J 2 ) or DHA and PPARγ antagonist GW9662. The mRNA and protein levels of IL‐6 and PPARγ were determined using Real‐time PCR and Western blot analyses. ROS levels were determined using DCF‐DA. The results showed that DHA inhibited cerulein‐induced IL‐6 expression and JAK2/STAT3 activation in AR42J cells. DHA induced the expression of PPARγ. PPARγ agonists inhibited cerulein‐induced IL‐6 expression. DHA reduces the levels of ROS and IL‐6, which was reversed by co‐treatment of PPARγ antagonist in cerulein‐stimulated AR42J cells. In conclusion, DHA inhibits Jak2/Stat3‐mediated IL‐6 expression by activating PPARγ and reducing ROS levels in pancreatic acinar cells. DHA may be beneficial for suppressing the development of pancreatitis by inhibiting cytokine expression in pancreatic acinar cells. Support or Funding Information This study was supported by a grant (NRF‐2015R1A2A2A01004855) from the NRF of Korea.