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PMID: 19501157 Published · ppublish English Evaluation Study Journal Article Research Support, N.I.H., Extramural

Dietary supplementation of omega-3 fatty acid-containing fish oil suppresses F2-isoprostanes but enhances inflammatory cytokine response in a mouse model of ovalbumin-induced allergic lung inflammation.

Free radical biology & medicine ·Vol. 47 ·No. 5 ·2009-09-01 ·Pages 622-8

Yin H, Liu W, Goleniewska K, Porter NA, Morrow JD, Peebles RS

Abstract

Epidemiological and clinical evidence has suggested that increased dietary intake of fish oil containing omega-3 fatty acids including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may be associated with a reduced risk of asthma. However, interventional studies on these effects have been equivocal and controversial. Free radical oxidation products of lipids and cyclooxygenases-derived prostaglandins are believed to play an important role in asthma, and fish oil supplementation may modulate the levels of these critical lipid mediators. We employed a murine model of allergic inflammation produced by sensitization to ovalbumin (OVA) to study the effects of fish oil supplementation on airway inflammation. Our studies demonstrated that omega-3 fatty acids were dose dependently incorporated into mouse lung tissue after dietary supplementation. We examined the oxidative stress status by measuring the levels of isoprostanes (IsoPs), the gold standard for oxidative stress in vivo. OVA challenge caused significant increase of F(2)-IsoPs in mouse lung, suggesting an elevated level of oxidative stress. Compared to the control group, fish oil supplementation led to a significant reduction of F(2)-IsoP (from arachidonic acid) with a concomitant increase of F(3)-IsoPs (from EPA) and F(4)-IsoPs (from DHA). Surprisingly, however, fish oil supplementation enhanced production of proinflammatory cytokine IL-5 and IL-13. Furthermore, fish oil supplementation suppressed the production of pulmonary protective PGE(2) in the bronchoalveolar lavage (BAL) while the level of urinary metabolites of the PGE(2) was increased. Our data suggest that augmented lung inflammation after fish oil supplementation may be due to the reduction of PGE(2) production in the lung and these dichotomous results bring into question the role of fish oil supplementation in the treatment of asthma.

MeSH Terms
Animals Body Composition/drug effects Cytokines/metabolism Dietary Supplements Down-Regulation/drug effects F2-Isoprostanes/metabolism Fatty Acids, Omega-3/administration & dosage,pharmacology Female Fish Oils/administration & dosage,chemistry,pharmacology Hypersensitivity/diet therapy,metabolism Inflammation Mediators/metabolism Lipid Metabolism/drug effects Mice Mice, Inbred BALB C Models, Biological Ovalbumin Pneumonia/chemically induced,diet therapy,metabolism
Chemicals
Cytokines F2-Isoprostanes Fatty Acids, Omega-3 Fish Oils Inflammation Mediators Ovalbumin
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Yin Huiyong
Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA. [email protected]
Liu Wei
Goleniewska Kasia
Porter Ned A
Morrow Jason D
Peebles R Stokes
References (63)
63 references, click to expand
  1. Prenatal fatty acid status and immune development: the pathways and the evidence.
    Lipids. 2007 Sep;42(9):801-10 PMID: 17952480
  2. Requirement for IL-13 independently of IL-4 in experimental asthma.
    Science. 1998 Dec 18;282(5397):2261-3 PMID: 9856950
  3. Biomarkers of lipid peroxidation, airway inflammation and asthma.
    Eur Respir J. 2003 Jan;21(1):177-86 PMID: 12570126
  4. Isoprostanes: markers and mediators of oxidative stress.
    FASEB J. 2004 Dec;18(15):1791-800 PMID: 15576482
  5. Omega-3 and omega-6 fatty acid exposure from early life does not affect atopy and asthma at age 5 years.
    J Allergy Clin Immunol. 2007 Jun;119(6):1438-44 PMID: 17379291
  6. Mechanisms for the formation of isoprostane endoperoxides from arachidonic acid. "Dioxetane" intermediate versus beta-fragmentation of peroxyl radicals.
    J Biol Chem. 2003 May 9;278(19):16720-5 PMID: 12609993
  7. A series of prostaglandin F2-like compounds are produced in vivo in humans by a non-cyclooxygenase, free radical-catalyzed mechanism.
    Proc Natl Acad Sci U S A. 1990 Dec;87(23):9383-7 PMID: 2123555
  8. Evaluation of selective prostaglandin E2 (PGE2) receptor agonists as therapeutic agents for the treatment of asthma.
    Sci STKE. 2005 Sep 27;2005(303):pe47 PMID: 16189372
  9. Augmentation of bovine airway smooth muscle responsiveness to carbachol, KCl, and histamine by the isoprostane 8-iso-PGE2.
    Am J Physiol Lung Cell Mol Physiol. 2004 Nov;287(5):L1035-41 PMID: 15257985
  10. Protectin D1 is generated in asthma and dampens airway inflammation and hyperresponsiveness.
    J Immunol. 2007 Jan 1;178(1):496-502 PMID: 17182589
  11. Dietary polyunsaturated fatty acids in asthma- and exercise-induced bronchoconstriction.
    Eur J Clin Nutr. 2005 Dec;59(12):1335-46 PMID: 16047026
  12. Cysteinyl leukotrienes and 8-isoprostane in exhaled breath condensate of children with asthma exacerbations.
    Thorax. 2003 Jun;58(6):505-9 PMID: 12775861
  13. Human biochemistry of the isoprostane pathway.
    J Biol Chem. 2008 Jun 6;283(23):15533-7 PMID: 18285331
  14. Reactive oxygen species and airway inflammation.
    Free Radic Biol Med. 1990;9(3):235-43 PMID: 2272532
  15. Quantification of isoprostanes as indices of oxidant stress and the risk of atherosclerosis in humans.
    Arterioscler Thromb Vasc Biol. 2005 Feb;25(2):279-86 PMID: 15591226
  16. Diet as a risk factor for atopy and asthma.
    J Allergy Clin Immunol. 2005 Jun;115(6):1109-17; quiz 1118 PMID: 15940119
  17. Suppression of allergic inflammation by the prostaglandin E receptor subtype EP3.
    Nat Immunol. 2005 May;6(5):524-31 PMID: 15806106
  18. N-3 polyunsaturated fatty acids and inflammation: from molecular biology to the clinic.
    Lipids. 2003 Apr;38(4):343-52 PMID: 12848278
  19. An improved LC-MS/MS method for the quantification of prostaglandins E(2) and D(2) production in biological fluids.
    Anal Biochem. 2008 Jan 1;372(1):41-51 PMID: 17976507
  20. Effect of dietary enrichment with eicosapentaenoic and docosahexaenoic acids on in vitro neutrophil and monocyte leukotriene generation and neutrophil function.
    N Engl J Med. 1985 May 9;312(19):1217-24 PMID: 2985986
  21. Formation of F-ring isoprostane-like compounds (F3-isoprostanes) in vivo from eicosapentaenoic acid.
    J Biol Chem. 2006 May 19;281(20):14092-9 PMID: 16569632
  22. The isoprostanes: unique bioactive products of lipid peroxidation.
    Prog Lipid Res. 1997 Mar;36(1):1-21 PMID: 9373618
  23. Dietary supplementation with fish oil rich in omega-3 polyunsaturated fatty acids in children with bronchial asthma.
    Eur Respir J. 2000 Nov;16(5):861-5 PMID: 11153584
  24. Eicosapentaenoic acid inhibits prostaglandin D2 generation by inhibiting cyclo-oxygenase-2 in cultured human mast cells.
    Clin Exp Allergy. 1999 Aug;29(8):1129-35 PMID: 10457118
  25. Free radical-induced generation of isoprostanes in vivo. Evidence for the formation of D-ring and E-ring isoprostanes.
    J Biol Chem. 1994 Feb 11;269(6):4317-26 PMID: 8307999
  26. Vasoconstrictor responses, and underlying mechanisms, to isoprostanes in human and porcine bronchial arterial smooth muscle.
    Br J Pharmacol. 2003 Oct;140(4):759-63 PMID: 14504139
  27. Allergen-induced airway hyperresponsiveness mediated by cyclooxygenase inhibition is not dependent on 5-lipoxygenase or IL-5, but is IL-13 dependent.
    J Immunol. 2005 Dec 15;175(12):8253-9 PMID: 16339565
  28. The effect on human tumor necrosis factor alpha and interleukin 1 beta production of diets enriched in n-3 fatty acids from vegetable oil or fish oil.
    Am J Clin Nutr. 1996 Jan;63(1):116-22 PMID: 8604658
  29. Update on the role of prostaglandins in allergic lung inflammation: separating friends from foes, harder than you might think.
    J Allergy Clin Immunol. 2006 May;117(5):1036-9 PMID: 16675329
  30. Quantification of the major urinary metabolite of PGE2 by a liquid chromatographic/mass spectrometric assay: determination of cyclooxygenase-specific PGE2 synthesis in healthy humans and those with lung cancer.
    Anal Biochem. 2004 Nov 15;334(2):266-75 PMID: 15494133
  31. Preparation of isoprostanes and neuroprostanes.
    J Am Chem Soc. 2002 Oct 23;124(42):12424-5 PMID: 12381179
  32. Mass spectrometric quantification of F2-isoprostanes in biological fluids and tissues as measure of oxidant stress.
    Methods Enzymol. 1999;300:3-12 PMID: 9919502
  33. Dietary omega-3 polyunsaturated fatty acids inhibit phosphoinositide formation and chemotaxis in neutrophils.
    J Clin Invest. 1993 Feb;91(2):651-60 PMID: 8381824
  34. Allergen-induced synthesis of F(2)-isoprostanes in atopic asthmatics. Evidence for oxidant stress.
    Am J Respir Crit Care Med. 1999 Dec;160(6):1947-51 PMID: 10588611
  35. Mechanisms of free radical oxidation of unsaturated lipids.
    Lipids. 1995 Apr;30(4):277-90 PMID: 7609594
  36. Increased 8-isoprostane, a marker of oxidative stress, in exhaled condensate of asthma patients.
    Am J Respir Crit Care Med. 1999 Jul;160(1):216-20 PMID: 10390403
  37. Separation and identification of F2-isoprostane regioisomers and diastereomers by novel liquid chromatographic/mass spectrometric methods.
    J Chromatogr B Analyt Technol Biomed Life Sci. 2005 Nov 15;827(1):157-64 PMID: 15890564
  38. Cyclooxygenase inhibition increases interleukin 5 and interleukin 13 production and airway hyperresponsiveness in allergic mice.
    Am J Respir Crit Care Med. 2000 Aug;162(2 Pt 1):676-81 PMID: 10934105
  39. Resolvin E1 dampens airway inflammation and hyperresponsiveness in a murine model of asthma.
    Biochem Biophys Res Commun. 2008 Mar 7;367(2):509-15 PMID: 18190790
  40. Effect of low-to-moderate amounts of dietary fish oil on neutrophil lipid composition and function.
    Lipids. 2000 Jul;35(7):763-8 PMID: 10941877
  41. Quantification of F-ring isoprostane-like compounds (F4-neuroprostanes) derived from docosahexaenoic acid in vivo in humans by a stable isotope dilution mass spectrometric assay.
    J Chromatogr B Analyt Technol Biomed Life Sci. 2004 Jan 5;799(1):95-102 PMID: 14659440
  42. Cyclooxygenase inhibition augments allergic inflammation through CD4-dependent, STAT6-independent mechanisms.
    J Immunol. 2005 Jan 1;174(1):525-32 PMID: 15611279
  43. Regiochemistry of neuroprostanes generated from the peroxidation of docosahexaenoic acid in vitro and in vivo.
    J Biol Chem. 2005 Jul 15;280(28):26600-11 PMID: 15894799
  44. Increased exhaled 8-isoprostane in childhood asthma.
    Chest. 2003 Jul;124(1):25-31 PMID: 12853498
  45. Selective cyclooxygenase-1 and -2 inhibitors each increase allergic inflammation and airway hyperresponsiveness in mice.
    Am J Respir Crit Care Med. 2002 Apr 15;165(8):1154-60 PMID: 11956061
  46. Encapsulated fish oil enriched in alpha-tocopherol alters plasma phospholipid and mononuclear cell fatty acid compositions but not mononuclear cell functions.
    Eur J Clin Invest. 2000 Mar;30(3):260-74 PMID: 10692004
  47. Novel docosatrienes and 17S-resolvins generated from docosahexaenoic acid in murine brain, human blood, and glial cells. Autacoids in anti-inflammation.
    J Biol Chem. 2003 Apr 25;278(17):14677-87 PMID: 12590139
  48. N-3 polyunsaturated fatty acids and allergic disease.
    Curr Opin Clin Nutr Metab Care. 2004 Mar;7(2):123-9 PMID: 15075701
  49. Clinical efficacy of n-3 fatty acid supplementation in patients with asthma.
    J Am Diet Assoc. 2005 Jan;105(1):98-105 PMID: 15635353
  50. Prostaglandin E2 inhibits eosinophil trafficking through E-prostanoid 2 receptors.
    J Immunol. 2008 Nov 15;181(10):7273-83 PMID: 18981149
  51. New insights regarding the autoxidation of polyunsaturated fatty acids.
    Antioxid Redox Signal. 2005 Jan-Feb;7(1-2):170-84 PMID: 15650406
  52. Novel docosanoids inhibit brain ischemia-reperfusion-mediated leukocyte infiltration and pro-inflammatory gene expression.
    J Biol Chem. 2003 Oct 31;278(44):43807-17 PMID: 12923200
  53. Role of oxygen radicals on bronchial asthma.
    Curr Drug Targets Inflamm Allergy. 2005 Aug;4(4):505-9 PMID: 16101530
  54. n-3 polyunsaturated fatty acids, inflammation, and inflammatory diseases.
    Am J Clin Nutr. 2006 Jun;83(6 Suppl):1505S-1519S PMID: 16841861
  55. Omega-3 Fatty acids and airway hyperresponsiveness in asthma.
    J Altern Complement Med. 2004 Dec;10(6):1067-75 PMID: 15674003
  56. Leukotrienes and 8-isoprostane in exhaled breath condensate of children with stable and unstable asthma.
    J Allergy Clin Immunol. 2004 Feb;113(2):257-63 PMID: 14767439
  57. Three-year outcomes of dietary fatty acid modification and house dust mite reduction in the Childhood Asthma Prevention Study.
    J Allergy Clin Immunol. 2004 Oct;114(4):807-13 PMID: 15480319
  58. Cyclooxygenase inhibition during allergic sensitization increases STAT6-independent primary and memory Th2 responses.
    J Immunol. 2008 Oct 15;181(8):5360-7 PMID: 18832692
  59. Neuroprotectin D1: a docosahexaenoic acid-derived docosatriene protects human retinal pigment epithelial cells from oxidative stress.
    Proc Natl Acad Sci U S A. 2004 Jun 1;101(22):8491-6 PMID: 15152078
  60. Effect of omega-3 fatty acid concentrations in plasma on symptoms of asthma at 18 months of age.
    Pediatr Allergy Immunol. 2004 Dec;15(6):517-22 PMID: 15610365
  61. Assessment of oxidant stress in allergic asthma by measurement of the major urinary metabolite of F2-isoprostane, 15-F2t-IsoP (8-iso-PGF2alpha).
    Clin Exp Allergy. 2001 Mar;31(3):387-90 PMID: 11260149
  62. Oxidant stress modulates murine allergic airway responses.
    Free Radic Biol Med. 2006 Apr 1;40(7):1210-9 PMID: 16545689
  63. The effects of short- and long-term supplementation with fish oil on the incorporation of n-3 polyunsaturated fatty acids into cells of the immune system in healthy volunteers.
    Eur J Clin Nutr. 1993 Apr;47(4):255-9 PMID: 8491162
Article Info
Journal
Free radical biology & medicine
Abbr.
Free Radic Biol Med
ISSN
1873-4596
DOI
10.1016/j.freeradbiomed.2009.05.033
Email
[email protected]
Published
2009-09-01
Epub
2009-00-06
Pages
622-8
Language
English
Region
United States
NLM ID
8709159
PMCID
PMC2716436
Subset
IM
Grants
NIEHS NIH HHS · P01 ES013125-04 · United States
NIEHS NIH HHS · P01 ES013125-040002 · United States
NIGMS NIH HHS · GM15431 · United States
NIDDK NIH HHS · R01 DK048831 · United States
NIGMS NIH HHS · P01 GM015431 · United States
NIDDK NIH HHS · R01 DK048831-14 · United States
NIGMS NIH HHS · P50 GM015431-390005 · United States
NIEHS NIH HHS · ES13125 · United States
NIEHS NIH HHS · P01 ES013125 · United States
NIEHS NIH HHS · P30 ES000267 · United States
NIDDK NIH HHS · DK48831 · United States
NIEHS NIH HHS · P30 ES00267 · United States
NIGMS NIH HHS · P50 GM015431 · United States
External Links
PubMed source DOI: 10.1016/j.freeradbiomed.2009.05.033 PMC Full Text View journal details
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