title: Suppression of syndecan-1 expression in endothelial cells by tumor necrosis factor-alpha.
abstract: Syndecan-1 is a cell surface proteoglycan that binds extracellular matrix components and modulates the activity of heparin-binding growth factors. The expression of syndecan-1 is modified during development, carcinogenesis, and tissue regeneration. During cutaneous wound healing, syndecan-1 expression is transiently induced in newly-formed capillaries of granulation tissue as well as in proliferating keratinocytes. To study the mechanisms underlying this regulation we investigated the effects of several growth factors/cytokines on syndecan-1 expression in two human cell lines: EA.hy 926 endothelial cells and HaCaT keratinocytes. None of these factors significantly altered syndecan-1 mRNA expression in cultured keratinocytes, but when given to endothelial cells, tumor necrosis factor-alpha (TNF-alpha) specifically and dose-dependently suppressed syndecan-1 expression at both mRNA and protein levels. TNF-alpha reduced the amount of syndecan-1 protein in EA.hy 926 cells in both the presence and absence of serum and, at the same time, induced the expression of intercellular adhesion molecule-1 (ICAM-1). The suppressive effect of TNF-alpha on endothelial syndecan-1 expression was reproducible in in vivo experiments in which TNF-alpha-coated beads were administered directly to healing skin wounds of mice. Data supporting these findings were further obtained by injecting TNF-alpha into an experimental rat granulation tissue model. In this tissue TNF-alpha suppressed syndecan-1 mRNA expression by approximately 80%. These results indicate that TNF-alpha is capable of down-regulating syndecan-1 expression in endothelial cells both in vitro and in vivo and suggest that similar mechanisms may be responsible for the changes in syndecan-1 expression observed during various regenerative, developmental, and malignant processes.
authors.affiliation: Turku Center for Biotechnology and the Department of Medical Biochemistry, University of Turku, 20520 Turku, Finland.
authors.forename: V
authors.initials: V
authors.lastname: Kainulainen
authors.forename: L
authors.initials: L
authors.lastname: Nelimarkka
authors.forename: H
authors.initials: H
authors.lastname: Järveläinen
authors.forename: M
authors.initials: M
authors.lastname: Laato
authors.forename: M
authors.initials: M
authors.lastname: Jalkanen
authors.forename: K
authors.initials: K
authors.lastname: Elenius
mesh_terms: D000818:Animals; D002460:Cell Line; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011509:Proteoglycans / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D053668:Syndecan-1; D053667:Syndecans; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects / Q000235:genetics / Q000502:physiology
chemical_list: D008562:Membrane Glycoproteins; D011509:Proteoglycans; D012333:RNA, Messenger; C508241:SDC1 protein, human; C508242:Sdc1 protein, mouse; C508243:Sdc1 protein, rat; D053668:Syndecan-1; D053667:Syndecans; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1