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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Munksgaard International Publishers
    Experimental dermatology 13 (2004), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract:  Numerous recent investigations have pointed to a key role of the proinflammatory, pleiotropic cytokine tumor necrosis factor-α (TNF-α) in host defense and inflammatory processes. TNF overexpression has been found in lesional skin and in the circulation of psoriatic patients, and it was suggested that TNF-α is crucial in this and other immune diseases. Several approaches to inhibit TNF-α activity have been developed. These include three different neutralizing antibodies to TNF-α as well as three different soluble TNF-α receptors with characteristic properties designed to bind the 17-KDa soluble trimeric TNF-α and the 26-KDa membrane-bound form of TNF-α. Clinical trials have demonstrated significant antipsoriatic effects, and it is likely that blocking TNF-α will become an important therapeutic option. The data available from these trials contribute to further understanding of the disease by demonstrating the major role of TNF-α. An in-depth understanding of the regulation of TNF gene expression, protein production, receptor expression, and signaling pathways may lead to further, potentially important novel therapeutic strategies and antipsoriatic active small molecules, suitable for oral application in the future. Here we review the current knowledge of TNF biology, the approaches to inhibit TNF activity, and their clinical and immunological effects in psoriasis. In addition, the host-defense effects and chronic TNF-blocking activity are discussed.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Whereas the effects of interleukin (IL)-10 on several epithelial cell types are well established the capability of IL-10 to target keratinocytes (KC) is still a matter of debate. This, however, is of considerable importance, as IL-10 is a major anti-inflammatory, immunosuppressive cytokine with impact on the cutaneous homeostasis. Recently, IL-10 therapy has been proven to be clinically effective in psoriasis. Response to therapy is associated with normalization of typical parameters of keratinocyte pathology, but it is unclear whether this results from direct or indirect (secondary) effects. The purpose of the present study was to further investigate direct effects of IL-10 on keratinocytes and to address the reason for potential IL-10 unresponsiveness using keratinocytes such as the cell line HaCaT as well as primary foreskin keratinocytes. Using real time RT-PCR we demonstrated that IL-10 is neither able to induce its typical early gene product suppressor of cytokine signalling (SOCS) 3 nor to modulate the interferone (IFN)-γ-induced expression of SOCS 1 and 3. Although flow cytometric analyses showed binding of biotin labelled IL-10 to HaCaT cells, blocking experiments indicated that this resulted from unspecific binding. Moreover, scatchard plot analyses excluded specific binding to primary KC and HaCaT cells. Finally, real time mRNA analyses and Western blot experiments demonstrated that the absence of any specific binding results from the absence of clear IL-10R1 (alpha chain) expression, whereas the IL-10R2 (beta chain) is strongly expressed. Our data indicates that IL-10 unresponsiveness of keratinocytes could be explained by the lacking of functional IL-10 receptor expression and suggest that any IL-10 effects on these cells observed are indirectly mediated.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1546-170X
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Neutralization of proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α) or interleukin-1 (IL-1), decreases mortality in several animal models of sepsis. However, recent clinical trials did not show an unequivocal improvement in survival. In contrast to animals, which ...
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1546-170X
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] To the editor: In a recent issue of Nature Medicine, Schön et al. characterized efomycine M (Efo-M) isolated from Streptomyces BS1261 as a specific inhibitor of selectins. The authors showed that Efo-M at low micromolar concentrations is able to block E- and P-selectin interactions with ...
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1546-170X
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] The mechanism of immunodepression after brain injury is not yet clear. Here we demonstrate rapid systemic release of the immunoinhibitory cytokine interleukin-10, monocytic deactivation and a high incidence of infection in patients with ‘sympathetic storm’ due to acute accidental or ...
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-1173
    Keywords: Schlüsselwörter IL-10 ; Zytokine ; Inflammation ; Dermatitis ; Psoriasis ; Key words IL-10 ; Cytokines ; Inflammation ; Psoriasis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary In recent years the investigation of cytokines has been a focus of scientific interest in order to understand the pathogenesis of a variety of diseases. In additions cytokines are increasingly being used for therapeutic purposes, including dermatologic disorders. IL-10 is a recently described cytokine with anti- inflammatory and immunosuppressive qualities which plays an important role in immunoregulation. The overexpression of this mediator has been proven in some inflammatory dermatoses as well as in various skin tumors. These observations help to understand down regulatory events in hyperinflammatory conditions such as allergic or toxic dermatitis on the one hand and the suppression of an adequate anti-tumor response and thereby the progression of malignant tumors on the other hand. Recent investigations indicate a relative IL-10 deficiency in psoriasis. Initial therapeutic applications of IL-10 in psoriasis underline the pathophysiological importance of this cytokine.
    Notes: Zusammenfassung Seit einiger Zeit steht der Nachweis von Zytokinen auch in der Dermatologie im Mittelpunkt des wissenschaftlichen Interesses, insbesondere da diese ein besseres Verständnis der Pathogenese verschiedenster Erkrankungen erlauben. Darüber hinaus finden Zytokine zunehmend auch in der Dermatologie therapeutische Anwendung. Interleukin-(IL-) 10 ist ein erst seit kurzem bekanntes Zytokin, welches in der Immunregulation insbesondere durch seine antiinflammatorischen und immunsuppressiven Eigenschaften eine herausragende Rolle besitzt. Zwischenzeitlich konnte die verstärkte Expression dieses Mediators bei einigen entzündlichen Dermatosen ebenso wie bei verschiedenen Malignomen der Haut nachgewiesen werden. Diese Beobachtungen sind von Bedeutung, da sie einerseits die gewünschte Limitierung von hyperinflammatorischen Prozessen wie bei Ekzemen und Erythemen, andererseits aber auch die Unterdrückung einer adäquaten anti-Tumorantwort und somit Progredienz von Malignomen erklären könnten. Neuere Untersuchungen zeigen, daß bei der Psoriasis eine relative IL-10-Defizienz besteht. Erste therapeutische Applikationen von IL-10, die eine antipsoriatische Potenz vermuten lassen, sprechen auch hier für die pathophysiologische Bedeutung dieses Zytokins.
    Type of Medium: Electronic Resource
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