Tetaert Daniel, Pierre Maud, Demeyer Dominique, Husson Marie-Odile, Béghin Laurent, Galabert Claude, Gottrand Frédéric, Beermann Christopher, Guery Benoit, Desseyn Jean-Luc
INSERM, U837, JPARC Research Centre, IMPRT, place de Verdun, Lille, France.
Respir Res. 2007 Jun 5;8(1):39. doi: 10.1186/1465-9921-8-39.
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.
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.
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).
Our data suggest that n-3 PUFAs enriched diet represents an inexpensive strategy to prevent or treat mucin overproduction in pulmonary bacterial colonization.
气道中的粘蛋白分泌过多和黏液阻塞是囊性纤维化（CF）等慢性呼吸道疾病的特征性表现，并导致发病和死亡。在CF中，肺部铜绿假单胞菌的重复感染会加剧炎症并改变黏液特性。越来越多的证据表明，n-3多不饱和脂肪酸（PUFA）在许多炎症性疾病中具有抗炎特性，而n-6多不饱和脂肪酸花生四烯酸（AA）则有利于炎症介质如类二十烷酸前列腺素E2（PGE2）和白三烯B4（LTB4）的产生，这些介质可能会增强炎症反应。这表明n-3多不饱和脂肪酸可能对气道疾病中黏液过度产生具有保护作用。因此，我们推测n-3多不饱和脂肪酸可能会下调粘蛋白的表达。
我们设计了一种绝对实时PCR检测方法，以评估富含n-3或n-6多不饱和脂肪酸的5周饮食对铜绿假单胞菌感染小鼠肺部大粘蛋白表达的影响。
饮食中的脂肪酸对健康小鼠的粘蛋白基因表达没有影响。肺部感染导致分泌性凝胶形成粘蛋白Muc5b增加，膜结合粘蛋白Muc4减少。这些失调受到饮食脂肪酸的调节，n-3多不饱和脂肪酸对粘蛋白具有抑制作用（感染后4天，n-3多不饱和脂肪酸处理组和对照组的Muc5b分别从19倍增加到3.6×10⁵倍，对照组和n-3多不饱和脂肪酸处理组的Muc4分别从15倍减少到3.2×10⁴倍）。
我们的数据表明，富含n-3多不饱和脂肪酸的饮食是预防或治疗肺部细菌定植中粘蛋白过度产生的一种廉价策略。
