| Item type: | Article | ||||||||||||||||||||||||||||||||||||||||||
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| Journal or Publication Title: | The British journal of dermatology | ||||||||||||||||||||||||||||||||||||||||||
| Publisher: | BLACKWELL PUBLISHING | ||||||||||||||||||||||||||||||||||||||||||
| Place of Publication: | OXFORD | ||||||||||||||||||||||||||||||||||||||||||
| Volume: | 152 | ||||||||||||||||||||||||||||||||||||||||||
| Number of Issue or Book Chapter: | 6 | ||||||||||||||||||||||||||||||||||||||||||
| Page Range: | pp. 1134-42 | ||||||||||||||||||||||||||||||||||||||||||
| Date: | 2005 | ||||||||||||||||||||||||||||||||||||||||||
| Institutions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) | ||||||||||||||||||||||||||||||||||||||||||
| Identification Number: |
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| Classification: |
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| Keywords: | VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; SKIN EXPLANT MODEL; FAS LIGAND; T-LYMPHOCYTES; CULTURED KERATINOCYTES; CYTOKINE DYSREGULATION; COMPLICATIONS; MODULATION; ACTIVATION; apoptosis; graft-versus-host-disease; interferon-gamma; keratinocyte; skin | ||||||||||||||||||||||||||||||||||||||||||
| Dewey Decimal Classification: | 600 Technology > 610 Medical sciences Medicine | ||||||||||||||||||||||||||||||||||||||||||
| Status: | Published | ||||||||||||||||||||||||||||||||||||||||||
| Refereed: | Yes, this version has been refereed | ||||||||||||||||||||||||||||||||||||||||||
| Created at the University of Regensburg: | Yes | ||||||||||||||||||||||||||||||||||||||||||
| Item ID: | 14447 |
Web of ScienceAbstract
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 ...
Abstract
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-1 beta 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.
Metadata last modified: 29 Sep 2021 07:37
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