Abstract
Di-(2-ethylhexyl) phthalate (DEHP), a commonly used plasticizer, has an adjuvant effect in combination with ovalbumin (OVA). The adjuvant effect of DEHP has already been verified in our previous studies. In this study, to further investigate whether thymic stromal lymphopoietin (TSLP) was involved in the DEHP-adjuvant effect, DEHP was administered through a daily gavage exposure route. Mice were sensitized with ovalbumin (OVA) to trigger allergic responses, and an anti-TSLP monoclonal antibody was used to neutralize the effect of TSLP. Biomarkers including cytokines in bronchoalveolar lavage fluid (BALF), serum total IgE and TSLP content in the lung were detected. In addition, airway hyperreactivity and lung sections were examined. Collectively, these data indicated a salient Th2 response which was characterized by the upregulation of Th2-type cytokines, such as interleukin 4 (IL-4), IL-5 and IL-13. Moreover, the eosinophil number in BALF and the eosinophil cationic protein (ECP) in the lung were seen to have increased significantly. However, neutralization of TSLP with an anti-TSLP mAb reversed the adjuvant effect of DEHP on airway inflammation, structural alterations in the airway wall and increased airway hyperresponsiveness (AHR) to methacholine induced by the OVA allergen, suggesting that TSLP was an effective target site for suppressing the adjuvant effect of DEHP co-exposure.
Highlights
In recent years, reports of about the illegal use of the phthalate plasticizer, di-(2-ethylhexyl) phthalate (DEHP), have raised concerns among medical institutions, regulatory agencies and the public
Neutralization of thymic stromal lymphopoietin (TSLP) with an anti-TSLP monoclonal antibody (mAb) reversed the adjuvant effect of DEHP on airway inflammation, structural alterations in the airway wall and increased airway hyperresponsiveness (AHR) to methacholine induced by the OVA allergen, suggesting that TSLP was an effective target site for suppressing the adjuvant effect of DEHP co-exposure
TSLP neutralization reduced the DEHP-induced adjuvant effect on increased total IgE, OVA specific IgE and OVA specific IgG1 production in serum caused by OVA sensitization
Summary
Reports of about the illegal use of the phthalate plasticizer, di-(2-ethylhexyl) phthalate (DEHP), have raised concerns among medical institutions, regulatory agencies and the public. DEHP is widely used as a plasticizer in polyvinyl chloride from which it can leach and thence be absorbed by the human body. TSLP Neutralization Blocks the DEHP-Induced Immune Adjuvant Effect development of wheezing and allergic airway diseases, and has been shown to contribute to asthma occurrence in Sweden [1,2]. It was found that there is a dose-response relationship between DEHP concentrations in indoor dust and wheezing in preschool children in Bulgaria [3]. Many studies indicate that DEHP has an adjuvant effect with a coallergen which is characterized by the development of Th2 allergic responses [4,5,6,7]. The mechanism underlying the adjuvant effect of DEHP is still unclear
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