Environmental exposure to phthalates and Bisphenol A and the development of diabetes and asthma - an in vivo and in vitro study

Asthma, allergy and diabetes increased during the last decades. These diseases are caused by dysfunction of the immune system. Diabetes and allergic diseases could share common underlying immunological mechanisms and environmental causes. Our hypothesis i s that the two groups of chemicals, phthalates and bisphenol A (BPA), contribute to the development of diabetes, asthma and allergy. Exposure occurs broadly through both the indoor environment and food. Recent data have indicated an association between as thma and allergic symptoms in children and phthalates in residential dust. Also for BPA are there data indicating a link between exposure and diabetes as well as allergy. Through two experimental models we will investigate the effects of phthalates and BP A in relation to allergy, autoimmunity and inflammatory responses in lung cells. In vivo we will study the effects of phthalate and bisphenol A exposure in female mice with regard to development of insulin dependent (autoimmune) diabetes and allergy in o ffspring (as well as in the mother mice). Mice will be exposed perorally. Development of diabetes will be analyzed in mothers and the offspring together with specific IgE response to allergen. A number of relevant ex vivo investigations on cells and cytok ines will be conducted. In vitro we will examine the effects of the same substances on intracellular signal transduction pathways pertinent to airway inflammatory responses/asthma in different lung cell types from rats and humans. Also cells from the in vivo-model will be studied. The study will examine if the substances mediate their effects through receptor binding or more unspecific toxic effects. Release of inflammatory mediators, expression, activation and localization of components in relevant si gnal transduction pathways as well as cell death will be studied by immunologic, molecular biological as well as morphological techniques.