title: Docosahexaenoic acid exerts anti-inflammatory action on human eosinophils through peroxisome proliferator-activated receptor-independent mechanisms.
abstract: BACKGROUND
  Despite the fact that previous studies have indicated the significant roles of polyunsaturated fatty acids (PUFAs) in the immune system through peroxisome proliferator-activated receptor alpha (PPARα) and PPARγ, the biological functions and the mechanisms of action in eosinophils are poorly understood.
  
  
  METHODS
  We investigated the functional effects of docosahexaenoic acid (DHA, n-3 PUFA) on human peripheral blood eosinophils, using in vitro systems to test the hypothesis that DHA negatively regulates eosinophil mechanisms through PPARα and PPARγ.
  
  
  RESULTS
  Eosinophil apoptosis that spontaneously occurs under normal culture conditions was accelerated in the presence of DHA. In addition, eotaxin-directed eosinophil chemotactic responses were inhibited by pretreatment with DHA, disturbing both the velocity and the directionality of the cell movement. Pharmacological manipulations with specific antagonists indicated that the effects of DHA were not mediated through PPARα and PPARγ, despite the presence of these nuclear receptors. DHA also induced Fas receptor expression and caspase-3 activation that appears to be associated with a proapoptotic effect of DHA. Further, DHA rapidly inhibited the expression of eotaxin receptor C-C chemokine receptor 3 and eotaxin-induced calcium influx and phosphorylation of extracellular signal-regulated kinase. Interestingly, these inhibitory effects were not observed with linoleic acid (n-6 PUFA).
  
  
  CONCLUSIONS
  The data might explain one of the mechanisms found in previous research showing the favorable effects of n-3 PUFA supplementation on allergic diseases, and provide novel therapeutic strategies to treat eosinophilic disorders.
authors.affiliation: Department of Infection, Allergy, Clinical Immunology and Laboratory Medicine, Akita University Graduate School of Medicine, Akita, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Tanigai
authors.forename: Shigeharu
authors.initials: S
authors.lastname: Ueki
authors.forename: Junko
authors.initials: J
authors.lastname: Kihara
authors.forename: Rie
authors.initials: R
authors.lastname: Kamada
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Yamauchi
authors.forename: Andrei
authors.initials: A
authors.lastname: Sokal
authors.forename: Masahide
authors.initials: M
authors.lastname: Takeda
authors.forename: Wataru
authors.initials: W
authors.lastname: Ito
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kayaba
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Adachi
authors.forename: Ken
authors.initials: K
authors.lastname: Ohta
authors.forename: Junichi
authors.initials: J
authors.lastname: Chihara
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002118:Calcium; D053148:Caspase 3 / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D004281:Docosahexaenoic Acids / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004802:Eosinophilia / Q000097:blood; D004804:Eosinophils / Q000187:drug effects* / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D019787:Linoleic Acid / Q000494:pharmacology; D008297:Male; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism*; D010766:Phosphorylation; D054397:Receptors, CCR3 / Q000096:biosynthesis; D012720:Severity of Illness Index; D019014:fas Receptor / Q000096:biosynthesis
chemical_list: C515350:CCR3 protein, human; D047492:Peroxisome Proliferator-Activated Receptors; D054397:Receptors, CCR3; D019014:fas Receptor; D004281:Docosahexaenoic Acids; D019787:Linoleic Acid; D048049:Extracellular Signal-Regulated MAP Kinases; C505407:CASP3 protein, human; D053148:Caspase 3; D002118:Calcium