Inflammation Research

, Volume 61, Issue 1, pp 69–78 | Cite as

Di-(2-ethylhexyl) phthalate induces production of inflammatory molecules in human macrophages

  • Junko Nishioka
  • Chihiro Iwahara
  • Mikiko Kawasaki
  • Fumiko Yoshizaki
  • Hitoshi Nakayama
  • Kenji Takamori
  • Hideoki Ogawa
  • Kazuhisa Iwabuchi
Original Research Paper


Objective and design

To investigate whether di-(2-ethylhexyl) phthalate (DEHP) affects the production of inflammatory cytokines by human macrophages.

Materials and methods

Differentiated macrophage-like THP-1 cells were exposed to 200 μM DEHP for 3 h, followed by incubation in the presence or absence of opsonized zymosan A, and the concentrations of TNF-α, IL-1β, IL-8, and IL-6 in the culture media were determined by ELISA. DNA microarray and quantitative real-time RT-PCR analyses were performed to identify genes that showed changes in expression in response to DEHP.


DEHP treatment increased the concentrations of TNF-α, IL-1β, IL-8, and IL-6 in the media, regardless of whether the cells phagocytosed zymosan. DNA microarray analysis showed that DEHP increased the levels of expression of IL-8, CXCL1, CXCL2, CXCL3, CXCL6, CCL3, MMP3, MMP10, MMP14, and CSF2 mRNA, and real-time RT-PCR showed that DEHP significantly enhanced the levels of expression of IL-8, CXCL1, CXCL2, CXCL3, CXCL6, CCL3, MMP10, CSF2, TNF-α, IL-1β, and IL-6 mRNA in THP-1 cells. DEHP significantly induced translocation of p65 NF-κB into the nucleus.


DEHP enhances the production of inflammatory cytokines and chemokines by macrophages, and exacerbates their inflammatory response.


Di-(2-ethylhexyl) phthalate Macrophage Cytokines Chemokines DNA microarray analysis 



This study was supported in part by the Mizutani Foundation for Glycoscience (K.I.) and by a Grant-in-Aid (S0991013) from the Foundation of Strategic Research Projects in Private Universities from Ministry of Education, Culture, Sports, Science, and Technology, Japan.


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Copyright information

© Springer Basel AG 2011

Authors and Affiliations

  • Junko Nishioka
    • 1
  • Chihiro Iwahara
    • 1
  • Mikiko Kawasaki
    • 1
  • Fumiko Yoshizaki
    • 1
  • Hitoshi Nakayama
    • 2
  • Kenji Takamori
    • 1
  • Hideoki Ogawa
    • 1
  • Kazuhisa Iwabuchi
    • 1
    • 2
  1. 1.Institute for Environmental and Gender-Specific MedicineJuntendo University Graduate School of MedicineChibaJapan
  2. 2.Laboratory of BiochemistryJuntendo University School of Health Care and NursingChibaJapan

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