title: The peroxisome proliferator activated receptor δ is required for the differentiation of THP-1 monocytic cells by phorbol ester.
abstract: BACKGROUND
  PPARδ (NR1C2) promotes lipid accumulation in human macrophagesin vitroand has been implicated in the response of macrophages to vLDL. We have investigated the role of PPARδ in PMA-stimulated macrophage differentiation. The THP-1 monocytic cell line which displays macrophage like differentiation in response to phorbol esters was used as a model system. We manipulated the response to PMA using a potent synthetic agonist of PPARδ , compound F. THP-1 sub-lines that either over-expressed PPARδ protein, or expressed PPARδ anti-sense RNA were generated. We then explored the effects of these genetic modulations on the differentiation process.
  
  
  RESULTS
  The PPARδ agonist, compound F, stimulated differentiation in the presence of sub-nanomolar concentrations of phorbol ester. Several markers of differentiation were induced by compound F in a synergistic fashion with phorbol ester, including CD68 and IL8. Over-expression of PPARδ also sensitised THP-1 cells to phorbol ester and correspondingly, inhibition of PPARδ by anti-sense RNA completely abolished this response.
  
  
  CONCLUSIONS
  These data collectively demonstrate that PPARδ plays a fundamental role in mediating a subset of cellular effects of phorbol ester and supports observations from mouse knockout models that PPARδ is involved in macrophage-mediated inflammatory responses.
authors.affiliation: Biomedical Research Centre, University of Dundee, Ninewells Hospital and Medical School, Dundee. DD1 9SY, UK.
authors.forename: Helen
authors.initials: H
authors.lastname: Vosper
authors.affiliation: Biomedical Research Centre, University of Dundee, Ninewells Hospital and Medical School, Dundee. DD1 9SY, UK.|Medical Sciences Institute, University of Dundee, Nethergate, Dundee. DD1 4HN, UK.
authors.forename: Guennadi A
authors.initials: GA
authors.lastname: Khoudoli
authors.affiliation: Biomedical Research Centre, University of Dundee, Ninewells Hospital and Medical School, Dundee. DD1 9SY, UK.
authors.forename: Colin Na
authors.initials: CN
authors.lastname: Palmer