Bis (2-ethylhexyl) Phthalate (DEHP), the common chemical plasticizer with endocrine-disrupting effect, is ubiquitously present in the environment. Several epidemiologic studies have shown the association between plastic materials exposure and asthma and allergic rhinitis in children populations. However, the mechanisms involved in DEHP effect on allergic responses remain unclear. Dendritic cell (DC) is the key regulatory cell type for linking innate and adaptive immunity and is associated with the development of allergic diseases. This study examined the effect of mono-(-2-ethyl-5-hexyl) phthalate (MEHP), the primary metabolite of DEHP, on DC functions and also explored the role of peroxisome proliferator-activated receptor gamma (PPARg) in its effect. We observed that MEHP-conditioned BM-DCs displayed immature phenotypes, including low levels of MHC class II, CD80, and CD86. In addition, MEHP-conditioned BM-DCs secreted decreased levels of IL-10 and IL12 but enhanced IL-6 in response to LPS stimulation. These MEHP effects were shown in a PPARg dependent manner. Furthermore, MEHP-exposed mice developed more severe OVA-induced allergic lung inflammation compared to control group under conditions relevant to route and level of exposure in humans. These results suggested that DEHP may disturb physiologic function of DCs through, in part, PPARg-dependent mechanisms, supporting the importance of DEHP exposure on the regulation of DC's functions and allergic inflammation.
Date:
2016-08
Relation:
European Journal of Immunology. 2016 Aug;46(Suppl. 1):1109-1110.