IL-18-binding protein expression by endothelial cells and macrophages is up-regulated during active Crohn's disease
| Autor: | Daniela Novick, Boris Schwartsburd, Suzanne Herren, Jillian Harrison, Marie Kosco-Vilbois, Pierre Graber, Yolande Chvatchko, Tessa ten Hove, Anne Corbaz, Thomas Plitz, Charles A. Dinarello, Sander J. H. van Deventer, Soohyun Kim, Ilana Belzer |
|---|---|
| Přispěvatelé: | Extramural researchers |
| Jazyk: | angličtina |
| Rok vydání: | 2002 |
| Předmět: |
Gene isoform
Adult Male Umbilical Veins Colon Immunology Biology Proinflammatory cytokine Pathogenesis Downregulation and upregulation Crohn Disease Ileum Submucosa medicine Immunology and Allergy Humans Intestinal Mucosa Cells Cultured Aged Glycoproteins Aged 80 and over Crohn's disease Binding protein Macrophages Interleukin-18 Middle Aged medicine.disease Molecular biology Immunohistochemistry Up-Regulation medicine.anatomical_structure Intercellular Signaling Peptides and Proteins Interleukin 18 Female Endothelium Vascular |
| Zdroj: | Journal of immunology (Baltimore, Md., 168(7), 3608-3616. American Association of Immunologists |
| ISSN: | 0022-1767 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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