Transcriptional induction of junctional adhesion molecule-C gene expression in activated T cells
Publikation: Beitrag in Fachzeitschrift › Forschungsartikel › Beigetragen › Begutachtung
Beitragende
Abstract
Junctional adhesion molecule (JAM)-C is an Ig superfamily protein, which is involved in the regulation of various inflammatory and vascular events such as transendothelial leukocyte migration. JAM-C is expressed highly on the surface of endothelial cells and platelets, whereas expression in T lymphocytes is not well studied. To investigate the specific gene regulation of JAM-C in T lymphocytes, we determined JAM-C expression in quiescent and activated human T cells. Treatment with the polyclonal T cell activator PHA increased surface and total JAM-C expression in T cells time-and dose-dependently, as determined by flow cytometry and immunoblot analysis. In contrast, no up-regulation of JAM-A in activated T cells was detectable. The highest level of JAM-C up-regulation by PHA was observed in CD3+forkhead box P3+ and CD4 +CD25high T cells. Moreover, TCR activation with combined anti-CD3 and anti-CD28 stimulation induced JAM-C expression in T cells. JAM-C induction occurred at the mRNA level, suggesting a transcriptional regulatory mechanism of JAM-C expression. Accordingly, we studied the regulation of the human JAM-C gene promoter in transiently transfected T cells. Luciferase activity of a JAM-C promoter gene construct with three potential consensus sites for the transcription factor NFAT was induced markedly in activated T cells. Finally, pretreatment with two pharmacological inhibitors of calcineurin, cyclosporin A, and FK-506, but not with MAPK inhibitors, blocked JAM-C induction in activated T cells. In summary, JAM-C is up-regulated in activated human T lymphocytes via a transcriptional mechanism, suggesting a potential role of JAM-C in T cell functions.
Details
Originalsprache | Englisch |
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Seiten (von - bis) | 796-803 |
Seitenumfang | 8 |
Fachzeitschrift | Journal of Leukocyte Biology |
Jahrgang | 85 |
Ausgabenummer | 5 |
Publikationsstatus | Veröffentlicht - 1 Mai 2009 |
Peer-Review-Status | Ja |
Extern publiziert | Ja |
Externe IDs
Scopus | 65549094564 |
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PubMed | 19204148 |
Schlagworte
ASJC Scopus Sachgebiete
Schlagwörter
- Cell activation, Gene regulation, T lymphocytes