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A role for NF-KB-dependent gene transactivation in sunburn

Abeyama, K. (author), Eng, W. (author), Jester, J.V. (author), Vink, A.A. (author), Edelbaum, D. (author), Cockerell, C.J. (author), Bergstresser, P.R. (author), Takashima, A. (author)

Exposure of skin to ultraviolet (UV) radiation is known to induce NF-κB activation, but the functional role for this pathway in UV-induced cutaneous inflammation remains uncertain. In this study, we examined whether experimentally induced sunburn reactions in mice could be prevented by blocking UV-induced, NF-κB-dependent gene transactivation...

article 2000

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Infection of a canine macrophage cell line with Leishmania infantum: Determination of nitric oxide production and anti-leishmanial activity

Pinelli, E. (author), Gebhard, D. (author), Mommaas, A.M. (author), van Hoeij, M. (author), Langermans, J.A.M. (author), Ruitenberg, E.J. (author), Rutten, V.P.M.G. (author)

We have previously shown that resistance to Leishmania infantum in dogs is associated with a Th1 type of immune response. In this study, we use a canine macrophage cell line (030-D) that can readily be infected with this protozoan parasite. Our aim is to further characterize the effector mechanisms involved in killing of Leishmania parasite in...

article 2000

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The β-adrenoceptor agonist clenbuterol is a potent inhibitor of the LPS-induced production of TNF-α and IL-6 in vitro and in vivo

Izeboud, C.A. (author), Monshouwer, M. (author), van Miert, A.S.J.P.A.M. (author), Witkamp, R.F. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

Objective and Design: To investigate the suppressive effects of the β-agonist clenbuterol on the release of TNF-α and IL-6 in a lipopolysaccharide (LPS)-model of inflammation, both in vitro and in vivo. Material and Subjects: Human U-937 cell line (monocyte-derived macrophages), and male Wistar rats (200-250 g). Treatment: U-937 macrophages were...

article 1999

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Participation of β-adrenergic receptors on macrophages in modulation of LPS-induced cytokine release

Izeboud, C.A. (author), Mocking, J.A.J. (author), Monshouwer, M. (author), van Miert, A.S.J.P.A.M. (author), Witkamp, R.F. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

For several years it is known that β-adrenergic receptor agonists have anti-inflammatory effects. However, little is known about the role of β- adrenergic receptors on macrophages in the modulation of cytokine production by β-agonists during inflammation. In this study, the presence of β- receptors on PMA-differentiated U937 human macrophages,...

article 1999

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Fibrinolytic activity of human mesothelial cells is counteracted by rapid uptake of tissue-type plasminogen activator

Sitter, T. (author), Toet, K. (author), Quax, P. (author), Kooistra, T. (author), Gaubius instituut TNO (author)

Background. Human mesothelial cells (HMCs) have an important role in maintaining an adequately functioning fibrinolytic system in the peritoneal cavity by secreting the fibrinolytic enzymes tissue-type and urokinase-type plasminogen activator (t-PA and u-PA), as well as a specific PA inhibitor, PA inhibitor type 1 (PAI-1). In this study, we...

article 1999

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Genetic risk factors for autoimmune diseases

Feltkamp, T.E.W. (author), Aarden, L.A. (author), Lucas, C.J. (author), Verweij, C.L. (author), de Vries, R.R.P. (author), TNO Preventie en Gezondheid (author)

In most autoimmune diseases multigenic factors play a significant role in pathogenesis. Progress in identifying these genetic factors, many of which are located outside the major histocompatibility complex, was the subject of a recent meeting. Chemicals/CAS: Interleukin-10, 130068-27-8; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha

article 1999

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Effect of steroid hormones and retinoids on the formation of capillary-like tubular structures of human microvascular endothelial cells in fibrin matrices is related to urokinase expression

Lansink, M. (author), Koolwijk, P. (author), van Hinsbergh, V. (author), Kooistra, T. (author), Gaubius Instituut TNO (author)

Angiogenesis, the formation of new capillary blood vessels, is a feature of a variety of pathological processes. To study the effects of a specific group of hormones (all ligands of the steroid/retinoid/thyroid hormone receptor superfamily) on the angiogenic process in humans, we have used a model system in which human microvascular endothelial...

article 1998

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Differential regulation of interleukin-10 (IL-10) and IL-12 by glucocorticoids in vitro

Visser, J. (author), van Boxel-Dezaire, A. (author), Methorst, D. (author), Brunt, T. (author), de Kloet, E.R. (author), Nagelkerken, L. (author), TNO Preventie en Gezondheid (author)

Antigen-presenting cells are thought to modulate the development of Th1 and Th2 cells by the secretion of interleukin-10 (IL-10) and IL-12. Because glucocorticoids (GC) favor the development of Th2 responses, we determined whether dexamethasone (DEX) and hydrocortisone (HC) have differential effects on lipopolysaccharide-induced IL-10 and IL-12...

article 1998

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Inhibition of MMP synthesis by doxycycline and chemically modified tetracyclines (CMTs) in human endothelial cells

Hanemaaijer, R. (author), Visser, H. (author), Koolwijk, P. (author), Sorsa, T. (author), Salo, T. (author), Golub, L.M. (author), van Hinsbergh, V.W. (author), Gaubius Instituut TNO (author)

Doxycycline is a commonly used broad-spectrum antibiotic. Recently, it has been shown that it also inhibits the activity of mammalian collagenases and gelatinases, an activity unrelated to its antimicrobial efficacy. In this study, we show that doxycycline not only inhibits MMP-8 and MMP-9 (gelatinase B) activity, but also the synthesis of MMPs...

article 1998

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Expression of accessory molecules and cytokines in acute EAE in marmoset monkeys (Callithrix jacchus)

Laman, J.D. (author), van Meurs, M. (author), Schellekens, M.M. (author), de Boer, M. (author), Melchers, B. (author), Massacesi, L. (author), Lassmann, H. (author), Claassen, E. (author), 't Hart, B.A. (author), TNO Preventie en Gezondheid (author)

Accessory molecules and cytokines are involved in the immunopathogenesis of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) in rodent models, and are potential targets for immunotherapy. Evaluation of such experimental therapies requires appropriate animal models. Therefore, we analysed the expression of selected...

article 1998

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Tumor necrosis factor-alpha regulates expression of vascular endothelial growth factor receptor-2 and of its co-receptor neuropilin-1 in human vascular endothelial cells

TNO Preventie en Gezondheid (author), Giraudo, E. (author), Primo, L. (author), Audero, E. (author), Gerber, H.P. (author), Koolwijk, P. (author), Soker, S. (author), Klagsbrun, M. (author), Ferrara, N. (author), Bussolino, F. (author)

Tumor necrosis factor-alpha (TNF-alpha) modulates gene expression in endothelial cells and is angiogenic in vivo. TNF-alpha does not activate in vitro migration and proliferation of endothelium, and its angiogenic activity is elicited by synthesis of direct angiogenic inducers or of proteases. Here, we show that TNF-alpha up-regulates in a dose-...

article 1998

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Verocytotoxin inhibits mitogenesis and protein synthesis in purified human glomerular mesangial cells without affecting cell viability: Evidence for two distinct mechanisms

van Setten, P.A. (author), van Hinsbergh, V.W.M. (author), van den Heuvel, L.P.W.J. (author), van der Velden, T.J.A.N. (author), van de Kar, N.C.A.J. (author), Krebbers, R.J.M. (author), Karmali, M.A. (author), Monnens, L.A.H. (author), Gaubius Instituut TNO (author)

Acute renal failure is one of the hallmarks of the hemolytic uremic syndrome (HUS). Infection with a verocytotoxin (VT)- or Shiga-like toxin (SLT)-producing Escherichia coli has been strongly implicated in the etiology of the epidemic form of HUS. The functional receptor for these closely related toxins appears to be a glycosphingolipid,...

article 1997

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Matrix metalloproteinase-8 is expressed in rheumatoid synovial fibroblasts and endothelial cells: Regulation by tumor necrosis factor-alpha and doxycycline

Gaubius Instituut TNO (author), Hanemaaijer, R. (author), Sorsa, T. (author), Konttinen, Y.T. (author), Ding, Y. (author), Sutinen, M. (author), Visser, H. (author), van Hinsbergh, V.W.M. (author), Helaakoski, T. (author), Kainulainen, T. (author), Rönkä, H. (author), Tschesche, H. (author), Salo, T. (author)

Neutrophil collagenase (matrix metalloproteinase-8 or MMP-8) is regarded as being synthesized exclusively by polymorphonuclear neutrophils (PMN). However, in vivo MMP-8 expression was observed in mononuclear fibroblast- like cells in the rheumatoid synovial membrane. In addition, we detected MMP- 8 mRNA expression in cultured rheumatoid synovial...

article 1997

document

Functions of CD40 and its ligand, gp39 (CD40L)

Laman, J.D. (author), Claassen, E. (author), Noelle, R.J. (author), TNO Preventie en Gezondheid (author)

Initially, a role for the interaction between CD40, expressed on B cells, and gp39 (CD40L), expressed on activated T cells, has been defined in humoral immunity. CD40-CD40L interaction is an essential signal for B cell proliferation, expression of activation markers, immunoglobulin production, and isotype switching. CD40-CD40L interaction is...

article 1996

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Intraperitoneal coagulation and fibrinolysis during inflammation: In vivo and in vitro observations

Sitter, T. (author), Gödde, M. (author), Spannagl, M. (author), Fricke, H. (author), Kooistra, T. (author), Gaubius Instituut TNO (author)

We used continuous peritoneal dialysis (CAPD) as a model to study intraperitoneal fibrin turnover during peritonitis. Activation markers of coagulation and fibrinolysis including prothrombin fragment F1+2 (F1+2), thrombin antithrombin III complex (TAT), fibrin monomer (FM), and fibrin degradation products (FbDP) were measured in the peritoneal...

article 1996

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Effects of verocytotoxin-1 on nonadherent human monocytes: Binding characteristics, protein synthesis, and induction of cytokine release

van Setten, P.A. (author), Monnens, L.A.H. (author), Verstraten, R.G.G. (author), van den Heuvel, L.P.W.J. (author), van Hinsbergh, V.W.M. (author), Gaubius Instituut TNO (author)

The epidemic form of the hemolytic uremic syndrome (HUS) has been associated with a verocytotoxin producing Escherichia coli infection. Endothelial cell damage of glomeruli and arterioles of the kidney plays a central role in the pathogenesis of HUS. A number of observations in vivo and in vitro indicate that inflammatory mediators contribute to...

article 1996

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Migration of human antigen-presenting cells in a human skin graft onto nude mice model after contact sensitization

Hoefakker, S. (author), Balk, H.P. (author), Boersma, W.J.A. (author), van Joost, T. (author), Notten, W.R.F. (author), Claassen, E. (author), TNO Preventie en Gezondheid (author)

Fluorescent contact chemical allergens provoke sensitization after application on both syngeneic and allogeneic skin grafts in mice. We attempted to determine whether the functional activity in a contact sensitization response of human skin graft was affected at the level of antigen uptake and migration. After xenogeneic skin transplantation, we...

article 1995

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Tumor necrosis factor α induces endothelial galactosyl transferase activity and verocytotoxin receptors. Role of specific tumor necrosis factor receptors and protein kinase C

van de Kar, N.C.A.J. (author), Kooistra, T. (author), Vermeer, M. (author), Lesslauer, W. (author), Monnens, L.A.H. (author), van Hinsbergh, V.W.M. (author), TNO Preventie en Gezondheid (author)

Infections with verocytotoxin (VT) producing Escherichia coil have been strongly implicated in the epidemic form of hemolytic uremic syndrome (HUS). Endothelial damage plays a central role in the pathogenesis of HUS. In vitro studies have shown that VT can damage endothelial cells after interaction with its cellular receptor...

article 1995

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Inhibiting interleukin-1 and tumor necrosis factor-α does not reduce induction of plasminogen activator inhibitor type-1 by endotoxin in rats in vivo

Emeis, J.E. (author), Hoekzema, R. (author), de Vos, A.F. (author), TNO Preventie en Gezondheid (author)

In experimental animals and humans, intravenous (IV) injection of endotoxin induces large increases in circulating plasminogen activator inhibitor type-1 (PAI-1), a major inhibitor of blood fibrinolysis. A similar increase is seen after the injection of interleukin-1 (IL-1) or of tumor necrosis factor-α (TNF-α), suggesting that these cytokines...

article 1995

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Genistein reduces tumor necrosis factor α-induced plasminogen activator inhibitor-1 transcription but not urokinase expression in human endothelial cells

van Hinsbergh, V.W.M. (author), Vermeer, M. (author), Koolwijk, P. (author), Grimbergen, J. (author), Kooistra, T. (author), Gaubius Laboratory TNO Preventie en Gezondheid (author)

The plasminogen activator inhibitor PAI-1 is markedly elevated in vivo and in vitro upon exposure to the inflammatory mediators tumor necrosis factor α (TNFα), interleukin-1 (IL-1), and bacterial lipopolysaccharide. Here we report that the isoflavone compound genistein prevents the increase in synthesis of PAI-1 induced by these inflammatory...

article 1994