Allergic process

Abstract: Prostaglandin (PG) D(2) is the major cyclooxygenase metabolite of arachidonic acid produced by mast cells in response to allergen in diseases, such as asthma, atopic dermatitis, allergic rhinitis and allergic conjunctivitis. However, whether PGD(2) regulates allergic process per se, and, if so, whether it facilitates or down-regulates the disease process has remained unknown. PGD(2) exerts its actions by binding to two types of specific cell surface receptor. One is DP (the PGD receptor) and the other is chemoattractant receptor-homologous molecule expressed on Th2. Between the two, the DP receptor has been better characterized since its cDNA cloning in 1994, and novel class of DP antagonists have been and are being developed. Furthermore, mice deficient in DP were generated and have been subjected to several models of allergic diseases to reveal the role of PGD(2) in allergy. In this article, we summarize these findings and provide an overview of the current status of the DP receptor research to discuss the therapeutic potential of modulating the PGD(2)-DP pathway in allergic diseases.

Abstract: Genetic research in allergic disease has focused primarily on asthma and its associated phenotypes (eg, total IgE), with very little attention given to the presence or absence of concomitant allergic diseases, especially allergic rhinitis and atopic dermatitis. Because asthma, allergic rhinitis, and atopic dermatitis share common systemic characteristics, it is reasonable to propose that a number of susceptibility genes could contribute to the allergic process regardless of the specific clinical phenotype. Consequently, the many genetic linkages previously reported for asthma may not be specific for asthma per se but rather may reflect an overall predisposition for allergic disease. Finally, epidemiologic data suggest that asthma and allergic rhinitis represent a continuum of disease, whereby those individuals with less severe disease will express rhinitis without asthma and those individuals with more severe disease express more than 1 phenotype. Alternatively, it is plausible that, in addition to the "allergic disease genes," there are "phenotype-specific genes" or possibly certain combinations of susceptibility genes (eg, gene-gene interactions) that contribute to the expression of asthma, allergic rhinitis, or atopic dermatitis.

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.