Palmitoylethanolamide Supplementation during Sensitization Prevents Airway Allergic Symptoms in the Mouse.

Fiorentina Roviezzo,Elisabetta Caiazzo,Vincenzo Di Marzo,Andrea Guarino,Armando Ialenti,Valentina M Iacono,Pierangelo Orlando,Raffaele Capasso,Antonietta Rossi,Alessio Peritore,Angelo A Izzo,Maria A Riemma,Carla Cicala

doi:10.3389/fphar.2017.00857

Abstract

One important risk factor for the development of asthma is allergen sensitization. Recent increasing evidence suggests a prominent role of mast cells in asthma pathophysiology. Since Palmitoylethanolamide (PEA), an endogenous lipid mediator chemically related to – and co-released with- the endocannabinoid anandamide, behaves as a local autacoid down-regulator of mast cell activation and inflammation, we explored the possible contribution of PEA in allergic sensitization, by using ovalbumin (OVA) as sensitizing agent in the mouse. PEA levels were dramatically reduced in the bronchi of OVA-treated animals. This effect was coupled to a significant up-regulation of CB2 and GPR55 receptors, two of the proposed molecular PEA targets, in bronchi harvested from allergen-sensitized mice. PEA supplementation (10 mg/kg, 15 min before each allergen exposure) prevented OVA-induced bronchial hyperreactivity, but it did not affect IgE plasma increase. On the other hand, PEA abrogated allergen-induced cell recruitment as well as pulmonary inflammation. Evaluation of pulmonary sections evidenced a significant inhibitory action of PEA on pulmonary mast cell recruitment and degranulation, an effect coupled to a reduction of leukotriene C4 production. These findings demonstrate that allergen sensitization negatively affects PEA bronchial levels and suggest that its supplementation has the potential to prevent the development of asthma-like features.

Highlights

Asthma is a common disease which affects around 5% of the global population
In the light of the well-established role of mast cells in asthma pathogenesis and considering that PEA inhibits mast cell recruitment and degranulation, we have evaluated its role in allergen sensitization and inflammation
To demonstrate the extent to which allergic sensitization decreases PEA levels, BALB/c mice were sensitized and PEA levels were measured in bronchi harvested from vehicle- and OVAtreated mice (Figure 1A)

Summary

Introduction

Asthma is a common disease which affects around 5% of the global population. For the majority of patients symptoms can be controlled with a combination of inhaled corticosteroids, bronchodilators and LT modifiers (Wilson et al, 2006; Lang, 2015). For a long time mast cells have been considered critical only for the expression of immediate allergic reactions, such as anaphylaxis or the acute wheezing provoked by allergen challenge in subjects with atopic asthma; it has become evident that these cells contribute to the expression of both IgE-dependent late phase reactions and some important features of chronic allergic inflammation (Galli et al, 2005; BulfonePaus and Bahri, 2015). Mast cells participate in the initiation of such responses and can function as immunoregulatory cells. Via the secretion of these mediators, mast cells participate in the sensitization phase of the acquired immune response sustaining dendrite cell maturation, function and recruitment to local lymph nodes (Oskeritzian, 2015). Mast cells exert important functions by interacting with airway structures and influencing airway function (Bradding and Arthur, 2016; Virk et al, 2016)

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