title: Palmitoylethanolamide reduces inflammation and itch in a mouse model of contact allergic dermatitis.
abstract: In mice, 2,4-dinitrofluorobenzene (DNFB) induces contact allergic dermatitis (CAD), which, in a late phase, is characterized by mast cell (MC) infiltration and angiogenesis. Palmitoylethanolamide (PEA), an endogenous anti-inflammatory molecule, acts by down-modulating MCs following activation of the cannabinoid CB2receptor and peroxisome proliferator-activated receptor-α (PPAR-α). We have previously reported the anti-inflammatory effect of PEA in the early stage of CAD. Here, we examined whether PEA reduces the features of the late stage of CAD including MC activation, angiogenesis and itching. After sensitization to DNFB, female C57BL/6J mice underwent to three DNFB challenges at days 5, 12 and 19 and treatments were given at each challenge and for two more days. CAD was expressed as Δ increase in ear thickness between challenged and un-challenged mice. PEA (5mg/kg/i.p.) reduced: i) the DNFB-induced Δ increase; ii) the number of MCs per tissue area; iii) the expression of VEGF and its receptor Flk-1. These effects were reversed by co-administration of AM630 (1mg/kg/i.p.), a CB2antagonist, but not GW6471 (1mg/kg/i.p.), a PPAR-α antagonist. Finally, PEA reduced the number of ear scratchings 48h after DNFB challenge and this effect was reversed by both CB2 and PPAR-α antagonists, suggesting the involvement of both receptors. PEA, by reducing the features of late stage CAD in mice, may be beneficial in this pathological condition.
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Via D. Montesano 49, 80131 Napoli, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Vaia
authors.affiliation: Istituto di Chimica Biomolecolare (ICB), Consiglio Nazionale delle Ricerche, Via Campi Flegrei 34, 80078 Pozzuoli, NA, Italy; Endocannabinoid Research Group, Italy; Epitech Group S.p.A., Via Luigi Einaudi 13, 35030 Saccolongo, PD, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Petrosino
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Via D. Montesano 49, 80131 Napoli, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: De Filippis
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Via D. Montesano 49, 80131 Napoli, Italy.
authors.forename: Luana
authors.initials: L
authors.lastname: Negro
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Via D. Montesano 49, 80131 Napoli, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Guarino
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Via D. Montesano 49, 80131 Napoli, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Carnuccio
authors.affiliation: Istituto di Chimica Biomolecolare (ICB), Consiglio Nazionale delle Ricerche, Via Campi Flegrei 34, 80078 Pozzuoli, NA, Italy; Endocannabinoid Research Group, Italy. Electronic address: vdimarzo@icb.cnr.it.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Marzo
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Via D. Montesano 49, 80131 Napoli, Italy; Endocannabinoid Research Group, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Iuvone
mesh_terms: D000577:Amides; D000818:Animals; D002452:Cell Count; D017449:Dermatitis, Allergic Contact / Q000150:complications* / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D004139:Dinitrofluorobenzene / Q000009:adverse effects; D004195:Disease Models, Animal; D063388:Endocannabinoids / Q000378:metabolism; D004983:Ethanolamines / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000150:complications; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D010169:Palmitic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D011537:Pruritus / Q000150:complications*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D000577:Amides; D063388:Endocannabinoids; D004983:Ethanolamines; D010169:Palmitic Acids; D042461:Vascular Endothelial Growth Factor A; C005958:palmidrol; D004139:Dinitrofluorobenzene; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: Angiogenesis; Contact allergic dermatitis (CAD); Dinitrofluorobenzene (DNFB); Itch; Mast cells (MCs); Palmitoylethanolamide (PEA)