MAG-EPA resolves lung inflammation in an allergic model of asthma.
BACKGROUND
Asthma is a chronic disease characterized by airways hyperresponsiveness, inflammation and airways remodelling involving reversible bronchial obstruction. Omega-3 fatty acids and their derivatives are known to reduce inflammation in several tissues including lung.


OBJECTIVES
The effects of eicosapentaenoic acid monoacylglyceride (MAG-EPA), a newly synthesized EPA derivative, were determined on the resolution of lung inflammation and airway hyperresponsiveness in an in vivo model of allergic asthma.


METHODS
Ovalbumin (OVA)-sensitized guinea-pigs were treated or not with MAG-EPA administered per os. Isometric tension measurements, histological analyses, homogenate preparation for Western blot experiments or total RNA extraction for RT-PCR were performed to assess the effect of MAG-EPA treatments.


RESULTS
Mechanical tension measurements revealed that oral MAG-EPA treatments reduced methacholine (MCh)-induced bronchial hyperresponsiveness in OVA-sensitized guinea-pigs. Moreover, MAG-EPA treatments also decreased Ca(2+) hypersensitivity of bronchial smooth muscle. Histological analyses and leucocyte counts in bronchoalveolar lavages revealed that oral MAG-EPA treatments led to less inflammatory cell recruitment in the lung of OVA-sensitized guinea-pigs when compared with lungs from control animals. Results also revealed a reduction in mucin production and MUC5AC expression level in OVA-sensitized animals treated with MAG-EPA. Following MAG-EPA treatments, the transcript levels of pro-inflammatory markers such as IL-5, eotaxin, IL-13 and IL-4 were markedly reduced. Moreover, per os MAG-EPA administrations reduced COX2 over-expression in OVA-sensitized animals.


CONCLUSION AND CLINICAL RELEVANCE
We demonstrate that MAG-EPA reduces airway hyperresponsiveness and lung inflammation in OVA-sensitized animals, a finding consistent with a decrease in IL-4, IL-5, IL-13, COX-2 and MUC5AC expression levels in the lung. The present data suggest that MAG-EPA represents a new potential therapeutic strategy for resolving inflammation in allergic asthma.
['Morin|C|C|', 'Fortin|S|S|', 'Cantin|A M|AM|', 'Rousseau|É|É|']
D000485:Allergens D000818:Animals D018927:Anti-Asthmatic Agents D000893:Anti-Inflammatory Agents D001249:Asthma D016535:Bronchial Hyperreactivity D051546:Cyclooxygenase 2 D004195:Disease Models, Animal D005227:Fatty Acids D005260:Female D006168:Guinea Pigs D008168:Lung D008297:Male D050178:Monoglycerides D009077:Mucins D010047:Ovalbumin D019707:Receptors, Chemokine
asthma EPA MUC5AC COX-2 pro-inflammatory cytokines