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-PGF1α, PGF2α, 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 language | English |
|---|---|
| Pages (from-to) | 2169-2176 |
| Number of pages | 8 |
| Journal | Journal of Applied Physiology |
| Volume | 92 |
| Issue number | 5 |
| State | Published - Jul 2 2002 |
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Keywords
- Cystic fibrosis
- Cytokines
- Neutrophils
- Pseudomonas
ASJC Scopus subject areas
- Physiology
- Endocrinology
- Orthopedics and Sports Medicine
- Physical Therapy, Sports Therapy and Rehabilitation
Cite this
Characterization of LPS-induced lung inflammation in cftr-/- mice and the effect of docosahexaenoic acid. / Freedman, Steven D.; Weinstein, Deborah; Blanco, Paola G.; Martinez-Clark, Pedro; Urman, Serge; Zaman, Munir; Morrow, Jason D.; Alvarez, Juan G.
In: Journal of Applied Physiology, Vol. 92, No. 5, 02.07.2002, p. 2169-2176.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Characterization of LPS-induced lung inflammation in cftr-/- mice and the effect of docosahexaenoic acid
AU - Freedman, Steven D.
AU - Weinstein, Deborah
AU - Blanco, Paola G.
AU - Martinez-Clark, Pedro
AU - Urman, Serge
AU - Zaman, Munir
AU - Morrow, Jason D.
AU - Alvarez, Juan G.
PY - 2002/7/2
Y1 - 2002/7/2
N2 - 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-PGF1α, PGF2α, 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.
AB - 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-PGF1α, PGF2α, 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.
KW - Cystic fibrosis
KW - Cytokines
KW - Neutrophils
KW - Pseudomonas
UR - http://www.scopus.com/inward/record.url?scp=0036085182&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036085182&partnerID=8YFLogxK
M3 - Article
VL - 92
SP - 2169
EP - 2176
JO - Journal of Applied Physiology
JF - Journal of Applied Physiology
SN - 8750-7587
IS - 5
ER -