Abstract |
The pathogenesis of Crohn's disease (CD) remains under intense investigation. Increasing evidence suggests a role for mature IL-18 in the induction of proinflammatory cytokines and Th1 polarization in CD lesions. The aim of this study was to investigate the contribution of the IL-18-neutralizing (a and c) and non-neutralizing (b and d) isoforms of IL-18-binding protein (IL-18BP) during active CD. Intestinal endothelial cells and macrophages were the major source of IL-18BP within the submucosa, and this IL-18BP production was also found to be relevant to other types of endothelial cells (HUVEC) and macrophages (peripheral monocytes). IL-18BP messenger transcript and protein were significantly increased in surgically resected specimens from active CD compared with control patients, correlating with an up-regulation of IL-18. Analysis of the expression of the four IL-18BP isoforms as well as being free or bound to IL-18 was reported and revealed that unbound IL-18BP isoforms a and c and inactive isoform d were present in specimens from active CD and control patients while isoform b was not detected. IL-18/IL-18BP complex was also detected. Interestingly, although most was complexed, free mature IL-18 could still be detected in active CD specimens even in the presence of the IL-18BP isoform a/c. These results demonstrate that the appropriate neutralizing isoforms are present in the intestinal tissue of patients with active CD and highlights the complexity of IL-18/IL-18BP biology.
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Authors | Anne Corbaz, Tessa ten Hove, Suzanne Herren, Pierre Graber, Boris Schwartsburd, Ilana Belzer, Jillian Harrison, Thomas Plitz, Marie H Kosco-Vilbois, Soo-Hyun Kim, Charles A Dinarello, Daniela Novick, Sander van Deventer, Yolande Chvatchko |
Journal | Journal of immunology (Baltimore, Md. : 1950)
(J Immunol)
Vol. 168
Issue 7
Pg. 3608-16
(Apr 01 2002)
ISSN: 0022-1767 [Print] United States |
PMID | 11907126
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Glycoproteins
- Intercellular Signaling Peptides and Proteins
- Interleukin-18
- interleukin-18 binding protein
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Topics |
- Adult
- Aged
- Aged, 80 and over
- Cells, Cultured
- Colon
(immunology, metabolism, pathology)
- Crohn Disease
(immunology, metabolism, pathology)
- Endothelium, Vascular
(cytology, immunology, metabolism)
- Female
- Glycoproteins
(biosynthesis, blood, metabolism)
- Humans
- Ileum
(immunology, metabolism, pathology)
- Immunohistochemistry
- Intercellular Signaling Peptides and Proteins
- Interleukin-18
(antagonists & inhibitors, biosynthesis, metabolism)
- Intestinal Mucosa
(immunology, metabolism, pathology)
- Macrophages
(cytology, immunology, metabolism)
- Male
- Middle Aged
- Umbilical Veins
- Up-Regulation
(immunology)
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