Reference : Mucosal gene expression of cell adhesion molecules, chemokines, and chemokine receptors ...
Scientific congresses and symposiums : Paper published in a journal
Human health sciences : Gastroenterology & hepatology
http://hdl.handle.net/2268/101428
Mucosal gene expression of cell adhesion molecules, chemokines, and chemokine receptors in patients with inflammatory bowel disease before and after infliximab treatment.
English
Arijs, Ingrid [> > > >]
De Hertogh, Gert [> > > >]
Machiels, Kathleen [> > > >]
Van Steen, Kristel mailto [Université de Liège - ULg > Dép. d'électric., électron. et informat. (Inst.Montefiore) > Bioinformatique >]
Lemaire, Katleen [> > > >]
Schraenen, Anica [> > > >]
Van Lommel, Leentje [> > > >]
Quintens, Roel [> > > >]
Van Assche, Gert [> > > >]
Vermeire, Severine [> > > >]
Schuit, Frans [> > > >]
Rutgeerts, Paul [> >]
2011
Acta Gastro-Enterologica Belgica
Acta Medica Belgica
106
4
748-61
Yes (verified by ORBi)
International
0001-5644
Bruxelles
Belgique
Belgian Week 2011
Belgian Week 2011
[en] Adult ; Anti-Inflammatory Agents/therapeutic use ; Antibodies, Monoclonal/therapeutic use ; Blotting, Western ; Cell Adhesion Molecules/metabolism ; Chemokines/metabolism ; Colitis/metabolism ; Colitis, Ulcerative/metabolism ; Colon/drug effects/metabolism ; Crohn Disease/metabolism ; Down-Regulation ; Female ; Gene Expression/drug effects ; Humans ; Ileitis/metabolism ; Ileum/drug effects/metabolism ; Immunohistochemistry ; Inflammatory Bowel Diseases/drug therapy/metabolism ; Intestinal Mucosa/drug effects/metabolism ; Male ; Microarray Analysis ; Middle Aged ; Receptors, Chemokine/metabolism ; Reverse Transcriptase Polymerase Chain Reaction/methods ; Up-Regulation ; Young Adult
[en] OBJECTIVES: Inflammatory bowel disease (IBD) is characterized by a continuous influx of leukocytes into the gut wall. This migration is regulated by cell adhesion molecules (CAMs), and selective antimigration therapies have been developed. This study investigated the effect of infliximab therapy on the mucosal gene expression of CAMs in IBD. METHODS: Mucosal gene expression of 69 leukocyte/endothelial CAMs and E-cadherin was investigated in 61 IBD patients before and after first infliximab infusion and in 12 normal controls, using Affymetrix gene expression microarrays. Quantitative reverse transcriptase-PCR (qRT-PCR), immunohistochemistry, and western blotting were used to confirm the microarray data. RESULTS: When compared with control colons, the colonic mucosal gene expression of most leukocyte/endothelial adhesion molecules was upregulated and E-cadherin gene expression was downregulated in active colonic IBD (IBDc) before therapy, with no significant colonic gene expression differences between ulcerative colitis and colonic Crohn's disease. Infliximab therapy restored the upregulations of leukocyte CAMs in IBDc responders to infliximab that paralleled the disappearance of the inflammatory cells from the colonic lamina propria. Also, the colonic gene expression of endothelial CAMs and of most chemokines/chemokine receptors returned to normal after therapy in IBDc responders, and only CCL20 and CXCL1-2 expression remained increased after therapy in IBDc responders vs. control colons. When compared with control ileums, the ileal gene expression of MADCAM1, THY1, PECAM1, CCL28, CXCL1, -2, -5, -6, and -11, and IL8 was increased and CD58 expression was decreased in active ileal Crohn's disease (CDi) before therapy, and none of the genes remained dysregulated after therapy in CDi responders vs. control ileums. This microarray study identified a number of interesting targets for antiadhesion therapy including PECAM1, IL8, and CCL20, besides the currently studied alpha4beta7 integrin-MADCAM1 axis. CONCLUSIONS: Our data demonstrate that many leukocyte/endothelial CAMs and chemokines/chemokine receptors are upregulated in inflamed IBD mucosa. Controlling the inflammation with infliximab restores most of these dysregulations in IBD. These results show that at least part of the mechanism of anti-tumor necrosis factor-alpha therapy goes through downregulation of certain adhesion molecules.
http://hdl.handle.net/2268/101428
10.1038/ajg.2011.27

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