Transcriptional induction of junctional adhesion molecule-C gene expression in activated T cells.
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(+)CD25(high) 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.
Immenschuh
Stephan
S
Institute for Transfusion Medicine, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. immenschuh.stephan@mh-hannover.de
Naidu
Srivatsava
S
Chavakis
Triantafyllos
T
Beschmann
Heike
H
Ludwig
Ralf J
RJ
Santoso
Sentot
S
D001483:Base Sequence; D019703:Calcineurin / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D003001:Cloning, Molecular; D005786:Gene Expression Regulation; D006801:Humans; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism*; D024363:Transcription Initiation Site; D015533:Transcriptional Activation; D015854:Up-Regulation
D015815:Cell Adhesion Molecules; C448000:JAM3 protein, human; D019703:Calcineurin