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Diabetologia
Published in: Diabetologia 6/2004

01-06-2004 | Article

Human pancreatic duct cells can produce tumour necrosis factor-α that damages neighbouring beta cells and activates dendritic cells

Authors: B. Movahedi, M. Van de Casteele, N. Caluwé, G. Stangé, K. Breckpot, K. Thielemans, G. Vreugdenhil, C. Mathieu, D. Pipeleers

Published in: Diabetologia | Issue 6/2004

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Abstract

Aims/hypothesis

In the human pancreas, a close topographic relationship exists between duct cells and beta cells. This explains the high proportion of duct cells in isolated human islet preparations. We investigated whether human duct cells are a source of TNFα-mediated interactions with beta cells and immune cells. This cytokine has been implicated in the development of autoimmune diabetes in mice.

Methods

Human duct cells were isolated from donor pancreases and examined for their ability to produce TNFα following a stress-signalling pathway. Duct-cell-released TNFα was tested for its in vitro effects on survival of human beta cells and on activation of human dendritic cells.

Results

Exposure of human pancreatic duct cells to interleukin-1β (IL-1β) induces TNFα gene expression, synthesis of the 26,000 Mr TNFα precursor and conversion to the 17,000 Mr mature form, which is rapidly released. This effect is NO-independent and involves p38 MAPK and NF-κB signalling. Duct-cell-released TNFα contributed to cytokine-induced apoptosis of isolated human beta cells. It also induced activation of human dendritic cells.

Conclusions/interpretation

Human pancreatic duct cells are a potential source of TNFα that can cause apoptosis of neighbouring beta cells and initiate an immune response through activation of dendritic cells. They may thus actively participate in inflammatory and immune processes that threaten beta cells during development of diabetes or after human islet cell grafts have been implanted.
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Metadata
Title
Human pancreatic duct cells can produce tumour necrosis factor-α that damages neighbouring beta cells and activates dendritic cells
Authors
B. Movahedi
M. Van de Casteele
N. Caluwé
G. Stangé
K. Breckpot
K. Thielemans
G. Vreugdenhil
C. Mathieu
D. Pipeleers
Publication date
01-06-2004
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 6/2004
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-004-1426-3

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