dc.contributor.author |
Crifo, Bianca |
|
dc.contributor.author |
Schaible, Bettina |
|
dc.contributor.author |
Brown, Eric |
|
dc.contributor.author |
Halligan, Doug N |
|
dc.contributor.author |
Scholz, Carsten C |
|
dc.contributor.author |
Fitzpatrick, Susan F |
|
dc.contributor.author |
Kirwan, Anna |
|
dc.contributor.author |
Roche, Helen M |
|
dc.contributor.author |
Criscuoli, Mattia |
|
dc.contributor.author |
Naldini, Antonella |
|
dc.contributor.author |
Giffney, Hugh |
|
dc.contributor.author |
Crean, Daniel |
|
dc.contributor.author |
Blanco, Alfonso |
|
dc.contributor.author |
Cavadas, Miguel A |
|
dc.contributor.author |
Cummins, Eoin P. |
|
dc.contributor.author |
Fabian, Zsolt |
|
dc.contributor.author |
Taylor, Cormac T |
|
dc.date.accessioned |
2019-12-04T14:36:19Z |
|
dc.date.available |
2019-12-04T14:36:19Z |
|
dc.date.issued |
2019 |
|
dc.identifier.citation |
journalVolume=202;journalIssueNumber=5;journalTitle=JOURNAL OF IMMUNOLOGY;pagerange=1521-1530;journalAbbreviatedTitle=J IMMUNOL; |
|
dc.identifier.uri |
http://repo.lib.semmelweis.hu//handle/123456789/7997 |
|
dc.identifier.uri |
doi:10.4049/jimmunol.1800912 |
|
dc.description.abstract |
Hypoxia is a common and prominent feature of the microenvironment at sites of bacteria-associated inflammation in inflammatory bowel disease. The prolyl-hydroxylases (PHD1/2/3) and the asparaginyl-hydroxylase factor-inhibiting HIF are oxygen-sensing enzymes that regulate adaptive responses to hypoxia through controlling the activity of HIF and NF-kappa B-dependent transcriptional pathways. Previous studies have demonstrated that the pan-hydroxylase inhibitor dimethyloxalylglycine (DMOG) is effective in the alleviation of inflammation in preclinical models of inflammatory bowel disease, at least in part, through suppression of IL-1 beta induced NF-kappa B activity. TLR-dependent signaling in immune cells, such as monocytes, which is important in bacteria driven inflammation, shares a signaling pathway with IL-1 beta. In studies into the effect of pharmacologic hydroxylase inhibition on TLR-induced inflammation in monocytes, we found that DMOG selectively triggers cell death in cultured THP-1 cells and primary human monocytes at concentrations well tolerated in other cell types. DMOG-induced apoptosis was independent of increased caspase-3/7 activity but was accompanied by reduced expression of the inhibitor of apoptosis protein 1 (cIAP1). Based on these data, we hypothesize that pharmacologic inhibition of the HIF-hydroxylases selectively targets monocytes for cell death and that this may contribute to the anti-inflammatory activity of HIF-hydroxylase inhibitors. |
|
dc.format.extent |
1521-1530 |
|
dc.relation.ispartof |
urn:issn:0022-1767 |
|
dc.title |
Hydroxylase Inhibition Selectively Induces Cell Death in Monocytes |
|
dc.type |
Journal Article |
|
dc.date.updated |
2019-11-25T12:34:42Z |
|
dc.language.rfc3066 |
en |
|
dc.rights.holder |
NULL |
|
dc.identifier.mtmt |
30519824 |
|
dc.identifier.wos |
000459022800021 |
|
dc.contributor.department |
SE/AOK/I/Orvosi Vegytani, Molekuláris Biológiai és Patobiokémiai Intézet |
|
dc.contributor.institution |
Semmelweis Egyetem |
|