Vaia Massimo, Petrosino Stefania, De Filippis Daniele, Negro Luana, Guarino Andrea, Carnuccio Rosa, Di Marzo Vincenzo, Iuvone Teresa
Department of Pharmacy, University of Naples Federico II, Via D. Montesano 49, 80131 Napoli, Italy.
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.
Eur J Pharmacol. 2016 Nov 15;791:669-674. doi: 10.1016/j.ejphar.2016.10.005. Epub 2016 Oct 5.
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 CB receptor 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 CB antagonist, 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.
在小鼠中，2,4-二硝基氟苯（DNFB）可诱发接触性过敏性皮炎（CAD），在疾病后期，其特征为肥大细胞（MC）浸润和血管生成。棕榈酰乙醇胺（PEA）是一种内源性抗炎分子，通过下调大麻素CB受体和过氧化物酶体增殖物激活受体-α（PPAR-α）激活后的MC发挥作用。我们之前报道了PEA在CAD早期的抗炎作用。在此，我们研究了PEA是否能减轻CAD后期的特征，包括MC激活、血管生成和瘙痒。对DNFB致敏后，雌性C57BL/6J小鼠在第5、12和19天接受三次DNFB激发，并在每次激发时及之后再给予两天进行治疗。CAD表现为激发组和未激发组小鼠耳部厚度的Δ增加值。PEA（5mg/kg/腹腔注射）可降低：i）DNFB诱导的Δ增加值；ii）每组织面积的MC数量；iii）VEGF及其受体Flk-1的表达。这些作用可被CB拮抗剂AM630（1mg/kg/腹腔注射）共同给药逆转，但不能被PPAR-α拮抗剂GW6471（1mg/kg/腹腔注射）逆转。最后，PEA减少了DNFB激发后48小时耳部抓挠的次数，且CB2和PPAR-α拮抗剂均可逆转此作用，提示两种受体均参与其中。PEA通过减轻小鼠CAD后期的特征，可能对这种病理状况有益。
