Oleanolic acid controls allergic and inflammatory responses in experimental allergic conjunctivitis.
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.
Instituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas-Universidad de Valladolid, Valladolid, Spain.
Claudia
C
Córdova
Instituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas-Universidad de Valladolid, Valladolid, Spain.
Beatriz
B
Gutiérrez
Departamento de Biología Celular, Histología y Farmacología, Universidad de Valladolid, Valladolid, Spain.
Carmen
C
Martínez-García
Instituto de Ciencias del Corazón. Hospital Clínico Universitario, Valladolid, Spain.
Rubén
R
Martín
Departamento de Biología Celular, Histología y Farmacología, Universidad de Valladolid, Valladolid, Spain.
Patricia
P
Gallego-Muñoz
Instituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas-Universidad de Valladolid, Valladolid, Spain.
Marita
M
Hernández
Instituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas-Universidad de Valladolid, Valladolid, Spain.
María L
ML
Nieto
D000485:Allergens / Q000633:toxicity; D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D003228:Conjunctiva / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D003233:Conjunctivitis, Allergic / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D007114:Immunization; D007073:Immunoglobulin E / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D009828:Oleanolic Acid / Q000494:pharmacology*; D011058:Pollen / Q000633:toxicity
D000485:Allergens; D018926:Anti-Allergic Agents; D016207:Cytokines; D007073:Immunoglobulin E; D009828:Oleanolic Acid