Pfizer COVID-19 vaccine appointments are available to our patients. Sign up for Connect today to schedule your vaccination. Continue your routine care with us by scheduling an in-person appointment or Video Visit.

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

TitleA two-step induction of indoleamine 2,3 dioxygenase (IDO) activity during dendritic-cell maturation.
Publication TypeJournal Article
Year of Publication2005
AuthorsBraun D, Longman RS, Albert ML
JournalBlood
Volume106
Issue7
Pagination2375-81
Date Published2005 Oct 1
ISSN0006-4971
KeywordsCell Proliferation, Chromatography, High Pressure Liquid, Cytokines, Dendritic Cells, Dinoprostone, Enzyme Activation, Humans, Immunotherapy, Indoleamine-Pyrrole 2,3,-Dioxygenase, Lipid Metabolism, Lipopolysaccharides, Lymphocyte Activation, Monocytes, Receptors, Tumor Necrosis Factor, RNA, Messenger, Signal Transduction, Time Factors, Transcription, Genetic, Tryptophan, Tumor Necrosis Factor-alpha, Up-Regulation
Abstract

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.

DOI10.1182/blood-2005-03-0979
Alternate JournalBlood
PubMed ID15947091
PubMed Central IDPMC1895261
Grant ListGM07739 / GM / NIGMS NIH HHS / United States