Send to

Choose Destination
See comment in PubMed Commons below
Blood. 2005 Oct 1;106(7):2375-81. Epub 2005 Jun 9.

A two-step induction of indoleamine 2,3 dioxygenase (IDO) activity during dendritic-cell maturation.

Author information

Institut Pasteur, Paris, France.


Prostaglandins, a family of lipidic molecules released during inflammation, display immunomodulatory properties in several models. One use includes exposure of monocyte-derived dendritic cells (DCs) to a cocktail of cytokines that contains prostaglandin E2 (PGE2) for purposes of maturation; such cells are currently being used for cancer immunotherapy trials. Our analysis of the transcription profile of DCs matured in the presence of tumor necrosis factor alpha (TNFalpha) and PGE2 revealed a strong up-regulation of indoleamine 2-3 dioxygenase (IDO), an enzyme involved in tryptophan catabolism and implicated in both maternal and T-cell tolerance. Using quantitative assays to monitor levels of IDO mRNA, protein expression, and enzyme activity, we report that PGE2 induces mRNA expression of IDO; however, a second signal through TNF receptor (TNF-R) or a Toll-like receptor (TLR) is necessary to activate the enzyme. Interestingly, use of TNFalpha, lipopolysaccharide, or Staphylococcus aureus Cowan I strain (SAC) alone does not induce IDO. The effect of PGE2 is mediated by activation of adenylate cyclase via the Gs-protein-coupled receptor E prostanoid-2 (EP2). A better understanding of these regulatory mechanisms and the crosstalk between TNF-R/TLR and EP2 signaling pathways will provide insight into the regulation of T-cell activation by DCs and may help to improve existing immunotherapy protocols.

[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center