Linoleic acid supplementation results in increased arachidonic acid and eicosanoid production in CF airway cells and in cftr -/- transgenic mice

Munir M. Zaman, Camilia R. Martin, Charlotte Andersson, Abdul Q. Bhutta, Joanne E. Cluette-Brown, Michael Laposata, Steven D. Freedman

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Cystic fibrosis (CF) patients display a fatty acid imbalance characterized by low linoleic acid levels and variable changes in arachidonic acid. This led to the recommendation that CF patients consume a high-fat diet containing >6% linoleic acid. We hypothesized that increased conversion of linoleic acid to arachidonic acid in CF leads to increased levels of arachidonate-derived proinflammatory metabolites and that this process is exacerbated by increasing linoleic acid levels in the diet. To test this hypothesis, we determined the effect of linoleic acid supplementation on downstream proinflammatory biomarkers in two CF models: 1) in vitro cell culture model using 16HBE14o - sense [wild-type (WT)] and antisense (CF) human airway epithelial cells; and 2) in an in vivo model using cftr -/- transgenic mice. Fatty acids were analyzed by gas chromatography-mass spectrometry (GC/MS), and IL-8 and eicosanoids were measured by ELISA. Neutrophils were quantified in bronchoalveolar lavage fluid from knockout mice following linoleic acid supplementation and exposure to aerosolized Pseudomonas LPS. Linoleic acid supplementation increased arachidonic acid levels in CF but not WT cells. IL-8, PGE 2, and PGF secretion were increased in CF compared with WT cells, with a further increase following linoleic acid supplementation. cftr -/- Mice supplemented with 100 mg of linoleic acid had increased arachidonic acid levels in lung tissue associated with increased neutrophil infiltration into the airway compared with control mice. These findings support the hypothesis that increasing linoleic acid levels in the setting of loss of cystic fibrosis transmembrane conductance regulator (CFTR) function leads to increased arachidonic acid levels and proinflammatory mediators.

Original languageEnglish (US)
Pages (from-to)L599-L606
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume299
Issue number5
DOIs
StatePublished - Nov 2010

Keywords

  • Fatty acid metabolism
  • Inflammation
  • Prostaglandins

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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