Phthalate esters modulate the differentiation and maturation of mouse peripheral blood mononuclear cell-derived...

Phthalate esters, such as di-(2-ethylhexyl) phthalate (DEHP), are widespread environmental contaminants. Previously, we have observed that DEHP exacerbates dermatitis elicited by mite antigen in NC/Nga mice. Also, DEHP enhances the functions of bone marrow-derived dendritic cells (DCs) in vitro. The present study sought to investigate whether phthalate esters affect peripheral blood mononuclear cell (PBMC)-derived DCs of NC/Nga mice. First, we studied the time course of DC generation from PBMCs and the dose dependency of granulocyte macrophage colony-stimulating factor and interleukin-4, and then determined the conditions under which DC differentiation and maturation are moderately induced from PBMCs. Under the conditions determined above, DEHP at 10 μ m significantly inhibited the expression of DC differentiation and maturation markers, such as CD11c, CD40, CD80, CD86 and CD205, whereas mono-(2-ethylhexyl) phthalate, a metabolite of DEHP, did not. Furthermore, the effects of DEHP on PBMC-derived DCs were partially rescued by treatment with ICI 182,780, an estrogen receptor antagonist. Taken together, these results suggest that DEHP can modulate the differentiation and maturation of mouse PBMC-derived DCs at least partially through activation of the estrogen receptor under our experimental conditions.