Di-(2-ethylhexyl) phthalate affects immune cells from atopic prone mice in vitro

Toxicology. 2009 May 2;259(1-2):54-60. doi: 10.1016/j.tox.2009.02.002. Epub 2009 Feb 11.


Phthalate esters as plasticizers have been widespread in the environment and may be associated with development of allergic diseases such as asthma and atopic dermatitis. However, the underlying mechanisms have not been fully elucidated. The present study investigated the effects of di-(2-ethylhexyl) phthalate (DEHP) on immune cells from atopic prone NC/Nga mice in vitro. Bone marrow-derived dendritic cells (BMDC) as a professional antigen-presenting cell and splenocytes as mixture of immune cells were used. BMDC were differentiated by culture with granulocyte macrophage-colony stimulating factor (GM-CSF) in the presence of DEHP (0.1-10microM) for 6 days. In another experiments, BMDC were differentiated by culture with GM-CSF for 8 days then these BMDC were exposed to DEHP (0.1-100microM) for 24h. Splenocytes were exposed to DEHP for 24h (0.1-100microM) or 72h (0.1-1000nM). After the culture, the phenotypic markers and the function of BMDC and splenocytes were evaluated. BMDC differentiated in the presence of DEHP showed enhancement in the expression of MHC class II, CD86, CD11c and DEC205, and in their antigen-presenting activity. On the other hand, the function of the differentiated BMDC was not activated by DEHP although DEHP partly enhanced their expression of DEC205. DEHP-exposed splenocytes showed increases in their TCR and CD3 expression, interleukin-4 production, and antigen-stimulated proliferation. These results demonstrate that DEHP enhances BMDC differentiation but not activation and also enhances Th2 response in splenocytes from atopic prone mice. The enhancement might contribute to the aggravating effect of DEHP on allergic disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / immunology
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Dendritic Cells / drug effects*
  • Dendritic Cells / immunology
  • Dermatitis, Atopic / chemically induced*
  • Dermatitis, Atopic / immunology
  • Diethylhexyl Phthalate / administration & dosage
  • Diethylhexyl Phthalate / toxicity*
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation / drug effects
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
  • Male
  • Mice
  • Plasticizers / administration & dosage
  • Plasticizers / toxicity*
  • Spleen / cytology
  • Spleen / drug effects*
  • Spleen / immunology
  • Th2 Cells / drug effects
  • Th2 Cells / immunology
  • Time Factors


  • Plasticizers
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Diethylhexyl Phthalate