Show simple item record Crifo, Bianca Schaible, Bettina Brown, Eric Halligan, Doug N Scholz, Carsten C Fitzpatrick, Susan F Kirwan, Anna Roche, Helen M Criscuoli, Mattia Naldini, Antonella Giffney, Hugh Crean, Daniel Blanco, Alfonso Cavadas, Miguel A Cummins, Eoin P. Fabian, Zsolt Taylor, Cormac T 2019-12-04T14:36:19Z 2019-12-04T14:36:19Z 2019
dc.identifier.citation journalVolume=202;journalIssueNumber=5;journalTitle=JOURNAL OF IMMUNOLOGY;pagerange=1521-1530;journalAbbreviatedTitle=J IMMUNOL;
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 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

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