title: Phthalate esters modulate the differentiation and maturation of mouse peripheral blood mononuclear cell-derived dendritic cells.
abstract: 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.
authors.affiliation: Environmental Health Sciences Division, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibaraki, 305-8506, Japan. itotomo@nies.go.jp
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Ito
authors.forename: Ken-ichiro
authors.initials: K
authors.lastname: Inoue
authors.forename: Noriko
authors.initials: N
authors.lastname: Nishimura
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Takano
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D004051:Diethylhexyl Phthalate / Q000378:metabolism / Q000494:pharmacology*; D004952:Esters / Q000378:metabolism / Q000494:pharmacology; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism / Q000494:pharmacology; D015847:Interleukin-4 / Q000378:metabolism / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D010795:Phthalic Acids / Q000378:metabolism / Q000494:pharmacology; D011960:Receptors, Estrogen / Q000378:metabolism; D013997:Time Factors
chemical_list: D004952:Esters; D010795:Phthalic Acids; D011960:Receptors, Estrogen; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D004051:Diethylhexyl Phthalate