Dietary n-3 fatty acids have suppressive effects on mucin upregulation in mice infected with Pseudomonas aeruginosa.
BACKGROUND
Mucin hypersecretion and mucus plugging in the airways are characteristic features of chronic respiratory diseases like cystic fibrosis (CF) and contribute to morbidity and mortality. In CF, Pseudomonas aeruginosa superinfections in the lung exacerbate inflammation and alter mucus properties. There is increasing evidence that n-3 polyunsaturated fatty acids (PUFAs) exhibit anti-inflammatory properties in many inflammatory diseases while n-6 PUFA arachidonic acid (AA) favors inflammatory mediators such as eicosanoids prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) that may enhance inflammatory reactions. This suggests that n-3 PUFAs may have a protective effect against mucus over-production in airway diseases. Therefore, we hypothesized that n-3 PUFAs may downregulate mucins expression.


METHODS
We designed an absolute real-time PCR assay to assess the effect of a 5-week diet enriched either with n-3 or n-6 PUFAs on the expression of large mucins in the lungs of mice infected by P. aeruginosa.


RESULTS
Dietary fatty acids did not influence mucin gene expression in healthy mice. Lung infection induced an increase of the secreted gel-forming mucin Muc5b and a decrease of the membrane bound mucin Muc4. These deregulations are modulated by dietary fatty acids with a suppressive effect of n-3 PUFAs on mucin (increase of Muc5b from 19-fold up to 3.6 x 10(5)-fold for the n-3 PUFAs treated group and the control groups, respectively, 4 days post-infection and decrease of Muc4 from 15-fold up to 3.2 x 10(4)-fold for the control and the n-3 PUFAs treated groups, respectively, 4 days post-infection).


CONCLUSIONS
Our data suggest that n-3 PUFAs enriched diet represents an inexpensive strategy to prevent or treat mucin overproduction in pulmonary bacterial colonization.
Tetaert
Daniel
D
INSERM, U837, JPARC Research Centre, IMPRT, place de Verdun, Lille, France. tetaert@lille.inserm.fr
Pierre
Maud
M
Demeyer
Dominique
D
Husson
Marie-Odile
MO
Béghin
Laurent
L
Galabert
Claude
C
Gottrand
Frédéric
F
Beermann
Christopher
C
Guery
Benoit
B
Desseyn
Jean-Luc
JL
D000284:Administration, Oral; D000818:Animals; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009077:Mucins / Q000378:metabolism*; D011552:Pseudomonas Infections / Q000178:diet therapy / Q000378:metabolism*; D016896:Treatment Outcome; D015854:Up-Regulation / Q000187:drug effects
D015525:Fatty Acids, Omega-3; D009077:Mucins