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Oleanolic acid controls allergic and inflammatory responses in experimental allergic conjunctivitis.

Córdova C, Gutiérrez B, Martínez-García C, Martín R, Gallego-Muñoz P, Hernández M, Nieto ML - PLoS ONE (2014)

Bottom Line: The result of allergen exposure is a strong Th2-mediated response along with conjunctival mast cell degranulation and eosinophilic infiltration.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.

View Article: PubMed Central - PubMed

Affiliation: Instituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas-Universidad de Valladolid, Valladolid, Spain.

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 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.

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OA administration prevents development of allergic conjunctival inflammation.Light micrograph of conjunctival sections in mice from allergic untreated, OA5-treated and OA10-treated groups. Representative toluidine (A) and H-E (B) stained sections showed infiltration in palpebral conjunctiva of mast cells and eosinophils, respectively. (C, D) Number of degranulated mast cells/mm2 and eosinophils/mm2, respectively. In images, green bars = 50 μm. In inserts, red bars = 10 μm. * and **P<0.01 (n = 10, three independent experiments). Zone I: conjunctiva palpebral. Zone II: conjunctiva bulbar. * and +P<0.001 versus control zone I and zone II, respectively; ** and ++P<0.001 versus untreated EAC-mice zone I and zone II, respectively; and ***P<0.01 versus untreated EAC-mice zone I.
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pone-0091282-g002: OA administration prevents development of allergic conjunctival inflammation.Light micrograph of conjunctival sections in mice from allergic untreated, OA5-treated and OA10-treated groups. Representative toluidine (A) and H-E (B) stained sections showed infiltration in palpebral conjunctiva of mast cells and eosinophils, respectively. (C, D) Number of degranulated mast cells/mm2 and eosinophils/mm2, respectively. In images, green bars = 50 μm. In inserts, red bars = 10 μm. * and **P<0.01 (n = 10, three independent experiments). Zone I: conjunctiva palpebral. Zone II: conjunctiva bulbar. * and +P<0.001 versus control zone I and zone II, respectively; ** and ++P<0.001 versus untreated EAC-mice zone I and zone II, respectively; and ***P<0.01 versus untreated EAC-mice zone I.

Mentions: Histological findings demonstrated by toluidine blue staining the presence of numerous mast cells infiltrating lamina propria and stroma of conjunctiva in EAC mice, being most of them degranulated mast cells (Fig. 2A and C). In contrast, in the OA-treated EAC groups infiltrating mast cells were mainly granulated and the number of degranulated mast cells was significant lower, compared to untreated ones.


Oleanolic acid controls allergic and inflammatory responses in experimental allergic conjunctivitis.

Córdova C, Gutiérrez B, Martínez-García C, Martín R, Gallego-Muñoz P, Hernández M, Nieto ML - PLoS ONE (2014)

OA administration prevents development of allergic conjunctival inflammation.Light micrograph of conjunctival sections in mice from allergic untreated, OA5-treated and OA10-treated groups. Representative toluidine (A) and H-E (B) stained sections showed infiltration in palpebral conjunctiva of mast cells and eosinophils, respectively. (C, D) Number of degranulated mast cells/mm2 and eosinophils/mm2, respectively. In images, green bars = 50 μm. In inserts, red bars = 10 μm. * and **P<0.01 (n = 10, three independent experiments). Zone I: conjunctiva palpebral. Zone II: conjunctiva bulbar. * and +P<0.001 versus control zone I and zone II, respectively; ** and ++P<0.001 versus untreated EAC-mice zone I and zone II, respectively; and ***P<0.01 versus untreated EAC-mice zone I.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3974667&req=5

pone-0091282-g002: OA administration prevents development of allergic conjunctival inflammation.Light micrograph of conjunctival sections in mice from allergic untreated, OA5-treated and OA10-treated groups. Representative toluidine (A) and H-E (B) stained sections showed infiltration in palpebral conjunctiva of mast cells and eosinophils, respectively. (C, D) Number of degranulated mast cells/mm2 and eosinophils/mm2, respectively. In images, green bars = 50 μm. In inserts, red bars = 10 μm. * and **P<0.01 (n = 10, three independent experiments). Zone I: conjunctiva palpebral. Zone II: conjunctiva bulbar. * and +P<0.001 versus control zone I and zone II, respectively; ** and ++P<0.001 versus untreated EAC-mice zone I and zone II, respectively; and ***P<0.01 versus untreated EAC-mice zone I.
Mentions: Histological findings demonstrated by toluidine blue staining the presence of numerous mast cells infiltrating lamina propria and stroma of conjunctiva in EAC mice, being most of them degranulated mast cells (Fig. 2A and C). In contrast, in the OA-treated EAC groups infiltrating mast cells were mainly granulated and the number of degranulated mast cells was significant lower, compared to untreated ones.

Bottom Line: The result of allergen exposure is a strong Th2-mediated response along with conjunctival mast cell degranulation and eosinophilic infiltration.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.

View Article: PubMed Central - PubMed

Affiliation: Instituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas-Universidad de Valladolid, Valladolid, Spain.

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 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.

Show MeSH
Related in: MedlinePlus