Cytokine-inducible CD40 gene expression in vascular smooth muscle cells is mediated by nuclear factor kappaB and signal transducer and activation of transcription-1.
The interaction of T-lymphocytes expressing the CD40 ligand (CD154) and cells of the vessel wall expressing the corresponding receptor protein (CD40) may play an important role in chronic inflammation including arteriosclerosis. One way of interfering with CD40-CD154 signalling is to prevent CD40 expression, the regulation of which, however, has yet to be elucidated. Therefore, we studied CD40 expression in rat aortic cultured smooth muscle cells. Both CD40 mRNA and protein expression in these cells was markedly enhanced as early as 6 h after exposure to different pro-inflammatory cytokines. Experiments with actinomycin D and subsequent run-on analyses revealed that CD40 expression in response to these cytokines was regulated at the level of transcription. Moreover, electrophoretic mobility shift analyses along with the employment of transcription factor decoy oligodeoxynucleotides demonstrated that tumor necrosis factor alpha via nuclear kappaB and interferon-gamma via signal transducer and activator of transcription-1 up-regulate CD40 gene expression in rat aortic cultured smooth muscle cells.
Department of Cardiovascular Physiology, University of Goettingen, Germany.
R
R
Krzesz
A H
AH
Wagner
M
M
Cattaruzza
M
M
Hecker
D000818:Animals; D001011:Aorta / Q000166:cytology; D019013:CD40 Antigens / Q000096:biosynthesis*; D023201:CD40 Ligand; D016207:Cytokines / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004357:Drug Synergism; D015870:Gene Expression; D018836:Inflammation Mediators; D007371:Interferon-gamma / Q000494:pharmacology; D008024:Ligands; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050794:STAT1 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D019013:CD40 Antigens; D016207:Cytokines; D004268:DNA-Binding Proteins; D018836:Inflammation Mediators; D008024:Ligands; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D050794:STAT1 Transcription Factor; D015534:Trans-Activators; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D023201:CD40 Ligand; D007371:Interferon-gamma