| Dokumentenart: | Artikel | ||||||||||||||||||||||||||||||||||||||||||
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| Titel eines Journals oder einer Zeitschrift: | The British journal of dermatology | ||||||||||||||||||||||||||||||||||||||||||
| Band: | 152 | ||||||||||||||||||||||||||||||||||||||||||
| Nummer des Zeitschriftenheftes oder des Kapitels: | 6 | ||||||||||||||||||||||||||||||||||||||||||
| Seitenbereich: | S. 1134-42 | ||||||||||||||||||||||||||||||||||||||||||
| Datum: | 2005 | ||||||||||||||||||||||||||||||||||||||||||
| Institutionen: | Medizin > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) | ||||||||||||||||||||||||||||||||||||||||||
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| Dewey-Dezimal-Klassifikation: | 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin | ||||||||||||||||||||||||||||||||||||||||||
| Status: | Veröffentlicht | ||||||||||||||||||||||||||||||||||||||||||
| Begutachtet: | Ja, diese Version wurde begutachtet | ||||||||||||||||||||||||||||||||||||||||||
| An der Universität Regensburg entstanden: | Ja | ||||||||||||||||||||||||||||||||||||||||||
| Dokumenten-ID: | 14447 |
Zusammenfassung
BACKGROUND: Apoptosis of keratinocytes or intestinal epithelial cells is an important pathophysiological mechanism of organ damage during acute graft-versus-host disease. OBJECTIVES: To analyse in detail the mediators and their mutual interaction leading to keratinocyte apoptosis. METHODS: Experiments were performed using a keratinocyte cell line (HaCaT) and human skin explant cultures. RESULTS: ...
Zusammenfassung
BACKGROUND: Apoptosis of keratinocytes or intestinal epithelial cells is an important pathophysiological mechanism of organ damage during acute graft-versus-host disease. OBJECTIVES: To analyse in detail the mediators and their mutual interaction leading to keratinocyte apoptosis. METHODS: Experiments were performed using a keratinocyte cell line (HaCaT) and human skin explant cultures. RESULTS: Supernatants (SN) of major histocompatibility complex nonmatched mixed lymphocyte cultures (MLCs) induced apoptosis in HaCaT cells and also in keratinocytes from skin biopsies. Although both interferon (IFN)-gamma and Fas ligand (FasL) were detected in MLC-SN by enzyme-linked immunosorbent assay, the apoptosis-inducing capacity could be fully abrogated by neutralization of IFN-gamma, but not by neutralization of FasL. Recombinant (r) IFN-gamma induced HaCaT keratinocyte apoptosis in a dose- and time-dependent manner. Induction of HaCaT apoptosis by rFasL alone was induced only at higher doses than present in MLC-SN, but apoptosis was dramatically enhanced in the presence of rIFN-gamma. Further synergistic effects with IFN-gamma in the induction of apoptosis were also observed with agonistic antitumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) receptor 2 antibody, soluble TRAIL and TNF-alpha. However, in contrast to FasL and TRAIL, TNF-alpha alone did not induce HaCaT apoptosis. Interleukin-1beta and lipopolysaccharide did not enhance the apoptosis-inducing effect of IFN-gamma. Beside its apoptosis-inducing capacity in HaCaT cells, rIFN-gamma also induced autocrine IFN-gamma production, and combined treatment with IFN-gamma and TNF-alpha induced autocrine TNF-alpha production. Neutralization of autocrine IFN-gamma protected HaCaT cells from apoptosis. CONCLUSIONS: Taken together, our data suggest a central role for IFN-gamma in HaCaT keratinocyte apoptosis but also show the importance of co-acting mediators such as TNF-alpha, TRAIL and FasL, which potentiate the effect of paracrine and autocrine IFN-gamma and TNF-alpha release.
Metadaten zuletzt geändert: 29 Sep 2021 07:37
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