Open AccessTumour necrosis factor‐α stimulates expression of TNF‐α converting enzyme in endothelial cells
Author(s) -
Bzowska Monika,
Jura Natalia,
Lassak Adam,
Black Roy A.,
Bereta Joanna
Publication year - 2004
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.2004.04215.x
Subject(s) - tumor necrosis factor alpha , vascular endothelial growth inhibitor , cytokine , biology , receptor , microbiology and biotechnology , vascular endothelial growth factor , immune system , proinflammatory cytokine , cancer research , immunology , endocrinology , vascular endothelial growth factor a , inflammation , biochemistry , vegf receptors
Tumor necrosis factor‐α converting enzyme (ADAM17) is a major metalloproteinase involved in the shedding of several membrane‐bound cytokines and cytokine receptors. Interplay of cytokines and their soluble receptors might be an important regulatory element in the network of interactions responsible for maintaining homeostasis in the immune system. ADAM17 thus has the potential to participate in a broad range of immune reactions. We studied the mechanisms of ADAM17 activation in endothelial cells and found that pro‐inflammatory cytokines (tumor necrosis factor‐α, interleukin‐1β, interferon‐γ) and growth factors (epidermal growth factor, vascular endothelial growth factor) are able to upregulate transcription of ADAM17 and expression of ADAM17 protein. This process might constitute an important mechanism of regulation of ADAM17 activity. Stimulation of transcription, rather than increased ADAM17 mRNA stability, was responsible for increased levels of ADAM17 mRNA. Importantly, the increase in ADAM17 was accompanied by increased shedding of TNF‐Receptor I (p55) in tumor necrosis factor‐α‐stimulated endothelial cells. Therefore, ADAM17‐dependent depletion of membrane‐bound tumor necrosis factor receptors from endothelial cells might constitute a mechanism of self‐protection in states of prolonged immunostimulation.