Characterization of LPS-induced lung inflammation in cftr-/- mice and the effect of docosahexaenoic acid

Steven D. Freedman, Deborah Weinstein, Paola G. Blanco, Pedro Martinez-Clark, Serge Urman, Munir Zaman, Jason D. Morrow, Juan G. Alvarez

Research output: Contribution to journalArticle

64 Scopus citations

Abstract

The mechanism by which Pseudomonas causes excessive inflammation in the cystic fibrosis lung is unclear. We have reported that arachidonic acid is increased and docosahexaenoic acid (DHA) decreased in lung, pancreas, and ileum from cftr-/- mice. Oral DHA corrected this defect and reversed the pathology. To determine which mediators regulate inflammation in lungs from cftr-/- mice and whether inhibition occurs with DHA, cftr-/- and wild-type (WT) mice were exposed to aerosolized Pseudomonas lipopolysaccharide (LPS). After 2 days of LPS, tumor necrosis factor-α (TNF-α), macrophage inflammatory protein-2, and KC levels in bronchoalveolar lavage fluid were increased in cftr-/- compared with WT mice and not suppressed by pretreatment with oral DHA. Neutrophil levels were not different between cftr-/- and WT mice. After 3 days of aerosolized LPS, neutrophil concentration, TNF-α, and the eicosanoids 6-keto-PGF, PGF, PGE2, and thromboxane B2 were all increased in bronchoalveolar lavage fluid from cftr-/- mice compared with WT controls. Oral DHA had no significant effect on TNF-α levels in cftr-/- mice. In contrast, neutrophils and eicosanoids were decreased in cftr-/- but not in WT mice treated with DHA, indicating that the effects of DHA on these inflammatory parameters may be related to correction of the membrane lipid defect.

Original languageEnglish (US)
Pages (from-to)2169-2176
Number of pages8
JournalJournal of applied physiology
Volume92
Issue number5
DOIs
StatePublished - Jan 1 2002

Keywords

  • Cystic fibrosis
  • Cytokines
  • Neutrophils
  • Pseudomonas

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Orthopedics and Sports Medicine
  • Physical Therapy, Sports Therapy and Rehabilitation

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  • Cite this

    Freedman, S. D., Weinstein, D., Blanco, P. G., Martinez-Clark, P., Urman, S., Zaman, M., Morrow, J. D., & Alvarez, J. G. (2002). Characterization of LPS-induced lung inflammation in cftr-/- mice and the effect of docosahexaenoic acid. Journal of applied physiology, 92(5), 2169-2176. https://doi.org/10.1152/japplphysiol.00927.2001