Córdova Claudia, Gutiérrez Beatriz, Martínez-García Carmen, Martín Rubén, Gallego-Muñoz Patricia, Hernández Marita, Nieto María L
Instituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas-Universidad de Valladolid, Valladolid, Spain.
Departamento de Biología Celular, Histología y Farmacología, Universidad de Valladolid, Valladolid, Spain.
PLoS One. 2014 Apr 3;9(4):e91282. doi: 10.1371/journal.pone.0091282. eCollection 2014.
Pollen is the most common aeroallergen to cause seasonal conjunctivitis. The result of allergen exposure is a strong Th2-mediated response along with conjunctival mast cell degranulation and eosinophilic infiltration. Oleanolic acid (OA) is natural a triterpene that displays strong anti-inflammatory and immunomodulatory properties being an active anti-allergic molecule on hypersensitivity reaction models. However, its effect on inflammatory ocular disorders including conjunctivitis, has not yet been addressed. Hence, using a Ragweed pollen (RWP)-specific allergic conjunctivitis (EAC) mouse model we study here whether OA could modify responses associated to allergic processes. We found that OA treatment restricted mast cell degranulation and infiltration of eosinophils in conjunctival tissue and decreased allergen-specific Igs levels in EAC mice. Th2-type cytokines, secreted phospholipase A2 type-IIA (sPLA2-IIA), and chemokines levels were also significantly diminished in the conjunctiva and serum of OA-treated EAC mice. Moreover, OA treatment also suppressed RWP-specific T-cell proliferation. In vitro studies, on relevant cells of the allergic process, revealed that OA reduced the proliferative and migratory response, as well as the synthesis of proinflammatory mediators on EoL-1 eosinophils and RBL-2H3 mast cells exposed to allergic and/or crucial inflammatory stimuli such as RWP, sPLA2-IIA or eotaxin. Taken together, these findings demonstrate the beneficial activity of OA in ocular allergic processes and may provide a new intervention strategy and potential therapy for allergic diseases.
花粉是引起季节性结膜炎最常见的空气变应原。接触变应原的结果是强烈的Th2介导反应，同时伴有结膜肥大细胞脱颗粒和嗜酸性粒细胞浸润。齐墩果酸（OA）是一种天然三萜，具有很强的抗炎和免疫调节特性，是超敏反应模型中的一种活性抗过敏分子。然而，其对包括结膜炎在内的炎症性眼部疾病的影响尚未得到研究。因此，我们在这里使用豚草花粉（RWP）特异性变应性结膜炎（EAC）小鼠模型，研究OA是否可以改变与过敏过程相关的反应。我们发现，OA治疗可限制结膜组织中肥大细胞的脱颗粒和嗜酸性粒细胞的浸润，并降低EAC小鼠中变应原特异性免疫球蛋白水平。在接受OA治疗的EAC小鼠的结膜和血清中，Th2型细胞因子、分泌型磷脂酶A2-IIA型（sPLA2-IIA）和趋化因子水平也显著降低。此外，OA治疗还抑制了RWP特异性T细胞增殖。对过敏过程相关细胞的体外研究表明，OA可降低暴露于变应性和/或关键炎症刺激（如RWP、sPLA2-IIA或嗜酸性粒细胞趋化因子）的EoL-1嗜酸性粒细胞和RBL-2H3肥大细胞的增殖和迁移反应，以及促炎介质的合成。综上所述，这些发现证明了OA在眼部过敏过程中的有益作用，并可能为过敏性疾病提供一种新的干预策略和潜在治疗方法。
