title: Di-(2-ethylhexyl) phthalate induces production of inflammatory molecules in human macrophages.
abstract: OBJECTIVE
  To investigate whether di-(2-ethylhexyl) phthalate (DEHP) affects the production of inflammatory cytokines by human macrophages.
  
  
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  DEHP enhances the production of inflammatory cytokines and chemokines by macrophages, and exacerbates their inflammatory response.
authors: Institute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, Urayasu-shi, Chiba, Japan.
authors: Junko
authors: J
authors: Nishioka
authors: Chihiro
authors: C
authors: Iwahara
authors: Mikiko
authors: M
authors: Kawasaki
authors: Fumiko
authors: F
authors: Yoshizaki
authors: Hitoshi
authors: H
authors: Nakayama
authors: Kenji
authors: K
authors: Takamori
authors: Hideoki
authors: H
authors: Ogawa
authors: Kazuhisa
authors: K
authors: Iwabuchi
mesh_terms: D002448:Cell Adhesion; D018925:Chemokines / Q000378:metabolism; D003470:Culture Media; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D006967:Hypersensitivity; D007249:Inflammation / Q000188:drug therapy*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010795:Phthalic Acids / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D014158:Transcription, Genetic; D015054:Zymosan / Q000494:pharmacology
chemical_list: D018925:Chemokines; D003470:Culture Media; D016207:Cytokines; D016328:NF-kappa B; D010795:Phthalic Acids; D015054:Zymosan