Abstract

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 conjunctivits, 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.

Highlights

  • Allergic conjunctivitis (AC) is one of the most common ocular surface diseases

  • To address overall immunosuppression by Oleanolic acid (OA), we assessed levels of RWPspecific IgG, IgG1 and IgG2a antibodies in serum, finding similar results to those obtained for Ragweed pollen (RWP)-specific IgE antibodies

  • We examined the effect of OA on allergic conjunctivitis in a RWPinduced experimental allergic conjunctivitis (EAC) model as well as its effects in vitro on eosinophils and mast cells functions

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Summary

Introduction

Allergic conjunctivitis (AC) is one of the most common ocular surface diseases. The disease encompasses a variety of pathological conditions, and based on immunopathological mechanisms, it can be subdivided into seasonal and perennial allergic conjunctivitis [1]. AC is an abnormal immune-hypersensitivity response to allergens mainly pollen, animal dander and house dust mites, some food substances may trigger it. They have common immunopathogenic mechanisms characterized by IgEmediated mast cell degranulation and/or T-lymphocyte-mediated immune response. The development of new therapeutic strategies will be a valuable tool to achieve better control of the disease and, will improve healthcare outcome for patients with allergic conjunctivitis

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