title: Inhibitory mechanism of omega-3 fatty acids in pancreatic inflammation and apoptosis.
abstract: Oxidative stress is regarded as a major pathogenic factor in acute pancreatitis. Inflammation and apoptosis linked to oxidative stress has been implicated in cerulein-induced pancreatitis as an experimental model of acute pancreatitis. Recently, we found that reactive oxygen species mediate inflammatory cytokine expression and apoptosis of pancreatic acinar cells stimulated with cerulein. Omega-3 fatty acids show antioxidant action in various cells and tissues. In the present study, we investigated whether omega-3 fatty acids inhibit cytokine expression in cerulein-stimulated pancreatic acinar cells and whether omega-3 fatty acids suppress apoptotic cell death in pancreatic acinar cells exposed to hydrogen peroxide. We found that omega-3 fatty acids, such as docosahexaenoic acid (DHA) and alpha-linolenic acid (ALA), suppressed the expression of inflammatory cytokines (IL-1beta, IL-6) and inhibited the activation of transcription factor activator protein-1 in cerulein-stimulated pancreatic acinar cells. DHA and ALA inhibited DNA fragmentation, inhibited the decrease in cell viability, and inhibited the expression of apoptotic genes (p53, Bax, apoptosis-inducing factor) induced by hydrogen peroxide in pancreatic acinar cells. In conclusion, omega-3 fatty acids may be beneficial for preventing oxidative stress-induced pancreatic inflammation and apoptosis by inhibiting inflammatory cytokine and apoptotic gene expression of pancreatic acinar cells.
authors.affiliation: Department of Food and Nutrition, Brain Korea 21 Project, College of Human Ecology, Yonsei University, Seoul, Korea.
authors.forename: Kyung Suk
authors.initials: KS
authors.lastname: Park
authors.forename: Joo Weon
authors.initials: JW
authors.lastname: Lim
authors.forename: Hyeyoung
authors.initials: H
authors.lastname: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002108:Ceruletide / Q000494:pharmacology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D053938:DNA Fragmentation / Q000187:drug effects; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D024202:Electrophoretic Mobility Shift Assay; D015525:Fatty Acids, Omega-3 / Q000737:chemistry / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D017962:alpha-Linolenic Acid / Q000494:pharmacology; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D016207:Cytokines; D015525:Fatty Acids, Omega-3; D053583:Interleukin-1beta; D015850:Interleukin-6; D018808:Transcription Factor AP-1; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D017962:alpha-Linolenic Acid; D004281:Docosahexaenoic Acids; D002108:Ceruletide; D006861:Hydrogen Peroxide