Tools
Tools
Iachininoto, M., Nuzzolo, E., Bonanno, G., Mariotti, A., Procoli, A., Locatelli, F., Cristofaro, R. and Rutella, S. 
ORCID: 0000-0003-1970-7375,
2013.
Cyclooxygenase-2 (COX-2) inhibition constrains indoleamine 2,3-dioxygenase 1 (IDO1) activity in acute myeloid leukaemia cells.
Molecules, 18 (9), pp. 10132-10145.
ISSN 1420-3049
|
Text
6022_Rutella.pdf - Published version Download (918kB) | Preview |
Abstract
Indoleamine 2,3-dioxygenase 1 (IDO1) metabolizes L-tryptophan to kynurenines (KYN), inducing T-cell suppression either directly or by altering antigen-presenting-cell function. Cyclooxygenase (COX)-2, the rate-limiting enzyme in the synthesis of prostaglandins, is over-expressed by several tumours. We aimed at determining whether COX-2 inhibitors down-regulate the IFN-g-induced expression of IDO1 in acute myeloid leukaemia (AML) cells. IFN-γ at 100 ng/mL up-regulated COX-2 and IDO1 in HL-60 AML cells, both at mRNA and protein level. The increased COX-2 and IDO1 expression correlated with heightened production of prostaglandin (PG)E2 and kynurenines, respectively. Nimesulide, a preferential COX-2 inhibitor, down-regulated IDO1 mRNA/protein and attenuated kynurenine synthesis, suggesting that overall IDO inhibition resulted both from reduced IDO1 gene transcription and from inhibited IDO1 catalytic activity. From a functional standpoint, IFN-g-challenged HL-60 cells promoted the in vitro conversion of allogeneic CD4+CD25− T cells into bona fide CD4+CD25+FoxP3+ regulatory T cells, an effect that was significantly reduced by treatment of IFN-γ-activated HL-60 cells with nimesulide. Overall, these data point to COX-2 inhibition as a potential strategy to be pursued with the aim at circumventing leukaemia-induced, IDO-mediated immune dysfunction.
| Item Type: | Journal article | ||||
|---|---|---|---|---|---|
| Publication Title: | Molecules | ||||
| Creators: | Iachininoto, M., Nuzzolo, E., Bonanno, G., Mariotti, A., Procoli, A., Locatelli, F., Cristofaro, R. and Rutella, S. | ||||
| Publisher: | MDPI | ||||
| Date: | 22 August 2013 | ||||
| Volume: | 18 | ||||
| Number: | 9 | ||||
| ISSN: | 1420-3049 | ||||
| Identifiers: |
|
||||
| Divisions: | Schools > School of Science and Technology | ||||
| Record created by: | Jonathan Gallacher | ||||
| Date Added: | 12 Sep 2016 08:50 | ||||
| Last Modified: | 13 Oct 2017 13:33 | ||||
| URI: | https://irep.ntu.ac.uk/id/eprint/28441 |
Actions (login required)
 |
Edit View |
Views
Views per month over past year
Downloads
Downloads per month over past year
