Cis-9,trans-11-conjugated linoleic acid inhibits allergic sensitization and airway inflammation via a PPARgamma-related mechanism in mice.
Milk consumption from early childhood on has been found to be inversely correlated with allergic sensitization and the onset of bronchial asthma. We tested whether cis-9,trans-11-conjugated linoleic acid (c9,t11-CLA), naturally occurring in milk fat, may prevent allergic sensitization and inhibit airway inflammation in a murine asthma model. BALB/c mice were fed a diet enriched in 1 wt% of c9,t11-CLA or a control diet 7 d prior to and for 32 d during sensitization [d 1 and 14, 100 mg/L ovalbumin (OVA) in adjuvant vs. PBS] and airway challenges (d 28-30, 1% OVA in PBS vs. PBS). Subgroups of mice were coadministered 20 micromol/L of the selective PPARgamma antagonist GW9662 during each OVA challenge. C9,t11-CLA feeding resulted in significantly reduced IgE production and allergen-induced in vivo airway hyperresponsiveness. Further, less mucous plugging of segmental bronchi and significantly reduced interleukin-5 and eosinophils were determined in bronchoalveolar lavage fluids of c9,t11-CLA-fed mice. C9,t11-CLA feeding prevented the downregulation of PPARgamma mRNA in the lung tissues observed after allergen sensitization and airway challenges in control mice. The inhibitory effects of c9,t11-CLA on airway inflammation were partially prevented by coadministration of GW9962. Further, c9,t11-CLA feeding resulted in a significantly lower concentration of the eicosanoid precursor, arachidonic acid, in tissue lipids. These findings demonstrate that dietary c9,t11-CLA can reduce allergic airway inflammation, most likely via a PPARgamma-related mechanism and by reducing eicosanoid precursors. They give new insights into the fatty acid-mediated mechanism of immunomodulation and may represent a step toward an attractive novel strategy in the dietary prevention and treatment of allergic asthma.
Institute of Nutrition, Friedrich Schiller University, 07743 Jena, Germany.
Anke
A
Jaudszus
Martin
M
Krokowski
Peter
P
Möckel
Yasemin
Y
Darcan
Anzhela
A
Avagyan
Paolo
P
Matricardi
Gerhard
G
Jahreis
Eckard
E
Hamelmann
D000403:Airway Resistance; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D017931:DNA Primers / Q000235:genetics; D004042:Dietary Fats, Unsaturated / Q000494:pharmacology; D005260:Female; D006967:Hypersensitivity / Q000178:diet therapy / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D047495:PPAR gamma / Q000235:genetics / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012137:Respiratory System / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology
C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D017931:DNA Primers; D004042:Dietary Fats, Unsaturated; D044243:Linoleic Acids, Conjugated; D047495:PPAR gamma; D012333:RNA, Messenger; C046938:9,11-linoleic acid; D010047:Ovalbumin