The JI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     
 

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Edelstein, M. P.
Right arrow Articles by Duch, D. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Edelstein, M. P.
Right arrow Articles by Duch, D. S.

The Journal of Immunology, Vol 143, Issue 9 2969-2973, Copyright © 1989 by American Association of Immunologists

ARTICLES

Synergistic effects of phorbol ester and INF-gamma on the induction of indoleamine 2,3-dioxygenase in THP-1 monocytic leukemia cells

MP Edelstein, Y Ozaki and DS Duch
Department of Medicinal Biochemistry, Wellcome Research Laboratories, Research Triangle Park, NC 27709.

Indoleamine 2,3-dioxygenase (IDO) is a flavin-dependent enzyme which uses superoxide anion as a cosubstrate to catalyze the decyclization of the pyrrole ring of L-tryptophan to form formylkynurenine. This enzyme is induced in some tumor cells after treatment with IFN-gamma. The mechanism of induction of IDO in tumor cells by IFN-gamma was studied in THP-1 human monocytic leukemia cells. Before the addition of IFN- gamma, no IDO could be detected in these cells. Treatment of THP-1 cells with IFN-gamma produced an induction of IDO, with peak activity occurring 72 to 96 h after addition of IFN-gamma. Because phorbol esters are known to induce many enzymes in cells, most likely through the activation of protein kinase C, the effects of PMA on the induction of IDO were determined. PMA potentiated the IFN-gamma-induced elevation of IDO, but by itself, was unable to induce enzyme activity. Maximum induction of IDO in the presence of PMA and IFN-gamma was obtained by preexposure of the cells to PMA for 48 h before the addition of IFN- gamma. Maximum induction of IDO after the addition of IFN-gamma occurred 24 to 48 h after addition of the cytokine to the culture medium. However, the induction of IDO does not appear to be potentiated through the activation of protein kinase C, because the addition of the protein kinase C inhibitor H-7 had no effect on the induction of IDO when the cells were exposed to PMA and IFN-gamma. Moreover, diacylglycerol was unable to replace PMA in these studies. Studies with cAMP and cGMP analogs suggest a role for these compounds in the regulation of IDO expression.


This article has been cited by other articles:


Home page
 BloodHome page
P. Terness, J.-J. Chuang, T. Bauer, L. Jiga, and G. Opelz
Regulation of human auto- and alloreactive T cells by indoleamine 2,3-dioxygenase (IDO)-producing dendritic cells: too much ado about IDO?
Blood, March 15, 2005; 105(6): 2480 - 2486.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 1989 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 1989 by The American Association of Immunologists, Inc. All rights reserved.