Tumor necrosis factor-alpha gene expression and release in cultured human dermal microvascular endothelial cells.
Endothelial dysfunctions in the microcirculation are a common finding in the course of inflammatory disorders. These are, at least in part, mediated by endogenous agonists, e.g. tumor necrosis factor-alpha (TNF-alpha). As TNF-alpha mostly acts in an autocrine or paracrine fashion, it was tempting to speculate that microvascular endothelial cells synthesize and release this cytokine upon appropriate stimulation. In the present study, human dermal microvascular endothelial cells (HDMECs) expressed the TNF-alpha gene following incubation with interleukin-1beta (IL-1beta), lipopolysaccharids (LPSs), as well as a combination of IL-1beta, LPSs, and interferon-gamma (IFN-gamma), while IFN-gamma failed to exert an effect on TNF-alpha gene expression when given as a single stimulus. Transcription of the TNF-alpha gene was accompanied by an increase in TNF-alpha protein secretion into the cellular supernatant. As HDMECs were found to be a target of TNF-alpha, production of this cytokine by HDMECs may result in an autocrine activation loop that contributes to the deterioration of microcirculatory functions in infectious diseases and inflammatory skin disorders.
Department of Physiology, University of Bonn, Bonn, Germany. umvb01@uni-bonn.de
Georg
G
Hoffmann
Michaela
M
Schloesser
Monika
M
Czechowski
Wolfgang
W
Schobersberger
Christine
C
Fürhapter
Norbert
N
Sepp
D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000276:immunology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008833:Microcirculation / Q000276:immunology; D016133:Polymerase Chain Reaction; D012867:Skin / Q000098:blood supply*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism
D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma