Dalia Obeid - Academia.edu (original) (raw)
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Papers by Dalia Obeid
Oncogene, Jun 26, 2006
The transmembrane metalloproteases angiotensin-converting enzyme (ACE) and tumor necrosis factor-... more The transmembrane metalloproteases angiotensin-converting enzyme (ACE) and tumor necrosis factor-a (TNF-a)-converting enzyme (TACE/ADAM-17) have been associated with inflammation, cancer progression and angiogenesis. Few investigations into the regulation of these enzymes by physiological stimuli have been reported. In this study, we investigated the influence of interferons (IFNs) type I (a, b) and II (c) on ACE and TACE expression of human leukemic NB4 cells and monocytes. We assessed the expression of proteases by reverse transcriptase-polymerase chain reaction, enzyme-linked immunosorbent assay and immunofluorescence analyses. IFNc, but not type I IFNs, upregulated membrane ACE in a dose-and time-dependency and this was reflected by the increase of ACE enzymatic activity and ACE mRNA. ACE upregulation was dependent on protein synthesis. Treatment of the interferon responsive factor 1 (IRF1)unresponsive HepG2 cell line with IFNc did not affect ACE expression, thus suggesting the participation of the IRF1 signaling pathway in IFNc-mediated ACE upregulation in myeloid cells. In contrast, both types of IFNs, in a dose-and time-dependent manner, downregulated surface TACE without affecting TACE transcript. Soluble TACE was not detected in the medium of IFN-treated cells. IFNc-mediated decrease of surface TACE in NB4 cells was reversible, and correlated with an increase in intracellular TACE, suggesting that cell surface TACE was internalized in response to IFNs. These findings, showing the presence of IFN-dependent controlled mechanisms by which ACE and TACE levels are regulated in human normal and leukemic myeloid cells, may have implications in the context of current investigations on the therapeutic potential of IFNs.
L'enzyme de conversion de l'angiotensine (ACE/CD143) et la TNF-a converting enzyme (TACE/... more L'enzyme de conversion de l'angiotensine (ACE/CD143) et la TNF-a converting enzyme (TACE/ADAM-17) sont des proteases membranaires, presentes dans divers types cellulaires dont les monocytes du sang circulant. Les monocytes, en infiltrant les tissus leses, jouent un role crucial dans l'inflammation, le cancer et les maladies cardiovasculaires. ACE et TACE sont anormalement surexprimees dans certaines pathologies inflammatoires et tumorales. De par leur capacite a hydrolyser des peptides bioactifs, des composants matriciels et des proteines membranaires (procytokines, recepteurs de cytokines, molecules d'adherence), ACE et TACE apparaissent impliquees dans l'homeostase, l'inflammation et l'angiogenese. Peu d'etudes ont aborde la regulation de ACE et TACE. L'identification des mecanismes de regulation de ces proteases monocytaires pourrait conduire au developpement de composes anti inflammatoires susceptibles d'etre utilisables en medecine. Je me...
Current Bioactive Compounds, 2006
Oncogene, Jun 26, 2006
The transmembrane metalloproteases angiotensin-converting enzyme (ACE) and tumor necrosis factor-... more The transmembrane metalloproteases angiotensin-converting enzyme (ACE) and tumor necrosis factor-a (TNF-a)-converting enzyme (TACE/ADAM-17) have been associated with inflammation, cancer progression and angiogenesis. Few investigations into the regulation of these enzymes by physiological stimuli have been reported. In this study, we investigated the influence of interferons (IFNs) type I (a, b) and II (c) on ACE and TACE expression of human leukemic NB4 cells and monocytes. We assessed the expression of proteases by reverse transcriptase-polymerase chain reaction, enzyme-linked immunosorbent assay and immunofluorescence analyses. IFNc, but not type I IFNs, upregulated membrane ACE in a dose-and time-dependency and this was reflected by the increase of ACE enzymatic activity and ACE mRNA. ACE upregulation was dependent on protein synthesis. Treatment of the interferon responsive factor 1 (IRF1)unresponsive HepG2 cell line with IFNc did not affect ACE expression, thus suggesting the participation of the IRF1 signaling pathway in IFNc-mediated ACE upregulation in myeloid cells. In contrast, both types of IFNs, in a dose-and time-dependent manner, downregulated surface TACE without affecting TACE transcript. Soluble TACE was not detected in the medium of IFN-treated cells. IFNc-mediated decrease of surface TACE in NB4 cells was reversible, and correlated with an increase in intracellular TACE, suggesting that cell surface TACE was internalized in response to IFNs. These findings, showing the presence of IFN-dependent controlled mechanisms by which ACE and TACE levels are regulated in human normal and leukemic myeloid cells, may have implications in the context of current investigations on the therapeutic potential of IFNs.
L'enzyme de conversion de l'angiotensine (ACE/CD143) et la TNF-a converting enzyme (TACE/... more L'enzyme de conversion de l'angiotensine (ACE/CD143) et la TNF-a converting enzyme (TACE/ADAM-17) sont des proteases membranaires, presentes dans divers types cellulaires dont les monocytes du sang circulant. Les monocytes, en infiltrant les tissus leses, jouent un role crucial dans l'inflammation, le cancer et les maladies cardiovasculaires. ACE et TACE sont anormalement surexprimees dans certaines pathologies inflammatoires et tumorales. De par leur capacite a hydrolyser des peptides bioactifs, des composants matriciels et des proteines membranaires (procytokines, recepteurs de cytokines, molecules d'adherence), ACE et TACE apparaissent impliquees dans l'homeostase, l'inflammation et l'angiogenese. Peu d'etudes ont aborde la regulation de ACE et TACE. L'identification des mecanismes de regulation de ces proteases monocytaires pourrait conduire au developpement de composes anti inflammatoires susceptibles d'etre utilisables en medecine. Je me...
Current Bioactive Compounds, 2006