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Title: NOD macrophages produce high levels of inflammatory cytokines upon encounter of apoptotic or necrotic cells
Authors: Stoffels, Katinka
Overbergh, Lutgart
Giulietti, Annapaula
Kasran, Ahmad
Bouillon, Roger
Gysemans, Conny
Mathieu, Chantal # ×
Issue Date: 6-Jul-2004
Series Title: Journal of autoimmunity vol:23 issue:1 pages:9-15
Abstract: During the development of type 1 diabetes, pancreatic beta-cells are subject to an immune attack, leading to their apoptotic or necrotic cell death. Apoptotic beta-cells are also present during periods of tissue remodeling, such as in early life. Macrophages should clear apoptotic cells silently without production of pro-inflammatory cytokines. The aim of the present study was to investigate the cytokine pattern of NOD macrophages exposed to apoptotic or necrotic cells in vitro. In contrast to the limited response of macrophages from C57BL/6 or NOR mice, NOD macrophages reacted aberrantly to both necrotic and apoptotic cells, with secretion of inappropriately high amounts of IL1beta and TNFalpha. Further exploration of the macrophage behavior showed an excessive response of NOD macrophages when exposed to LPS (high iNOS and IL12p40 levels), accompanied by hyper-activation of NF-kappaB(p65). In contrast, NOD macrophages failed to up-regulate IL1beta and IL12p40 in response to IFNgamma. This failure correlated with low protein levels and a low phosphorylation state of STAT1alpha. We conclude that NOD macrophages have severely aberrant cytokine expression patterns that could contribute to the initiation or continuation of an immune attack towards the pancreatic beta-cells and thus onset and progression of type 1 diabetes.
URI: 
ISSN: 0896-8411
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Clinical and Experimental Endocrinology
Laboratory of Nephrology
Laboratory of Clinical Immunology
Medical Clerkships Centers
× corresponding author
# (joint) last author

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