| Dokumentenart: | Artikel | ||||||
|---|---|---|---|---|---|---|---|
| Titel eines Journals oder einer Zeitschrift: | The American Journal of Gastroenterology | ||||||
| Verlag: | W B SAUNDERS CO-ELSEVIER INC | ||||||
| Ort der Veröffentlichung: | PHILADELPHIA | ||||||
| Band: | 147 | ||||||
| Nummer des Zeitschriftenheftes oder des Kapitels: | 1 | ||||||
| Seitenbereich: | S. 172-183 | ||||||
| Datum: | Juli 2014 | ||||||
| Zusätzliche Informationen (Öffentlich): | See editorial on page 26. | ||||||
| Institutionen: | Medizin > Institut für Funktionelle Genomik > Lehrstuhl für Statistische Bioinformatik (Prof. Spang) Informatik und Data Science > Fachbereich Bioinformatik > Lehrstuhl für Statistische Bioinformatik (Prof. Spang) | ||||||
| Identifikationsnummer: |
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| Stichwörter / Keywords: | ANTI-CD3 MONOCLONAL-ANTIBODY; RECOMBINANT HUMAN INTERLEUKIN-10; VERSUS-HOST-DISEASE; T-CELLS; HUMANIZED ANTI-CD3; DOSE-ESCALATION; BONE-MARROW; PHASE-I; OKT3; VISILIZUMAB; Crohn's Disease; Ulcerative Colitis; Immune Regulation; IFN | ||||||
| Dewey-Dezimal-Klassifikation: | 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie | ||||||
| Status: | Veröffentlicht | ||||||
| Begutachtet: | Ja, diese Version wurde begutachtet | ||||||
| An der Universität Regensburg entstanden: | Zum Teil | ||||||
| Dokumenten-ID: | 30480 |
Web of ScienceZusammenfassung
BACKGROUND & AIMS: T cells mediate the development of inflammation in inflammatory bowel disease (IBD). We investigated the effects of an antibody against CD3 called otelixizumab, which induces immune tolerance, in intestinal mucosa samples from patients. METHODS: Intestinal tissues were isolated from patients undergoing routine endoscopy or from patients undergoing intestinal surgery for colon ...
Zusammenfassung
BACKGROUND & AIMS: T cells mediate the development of inflammation in inflammatory bowel disease (IBD). We investigated the effects of an antibody against CD3 called otelixizumab, which induces immune tolerance, in intestinal mucosa samples from patients. METHODS: Intestinal tissues were isolated from patients undergoing routine endoscopy or from patients undergoing intestinal surgery for colon cancer or IBD; healthy surrounding tissues were collected as controls. Isolated lamina propria mononuclear cells (LPMCs) and mucosal tissue explants were incubated with otelixizumab for 24 or 48 hours. Production of inflammatory cytokines was determined by enzyme-linked immunosorbent assay. Levels of 36 cytokines and chemokines and phosphorylation of 39 receptor tyrosine kinases and signaling molecules were measured using protein arrays. Immunoblot analysis was used to analyze T-cell transcription factors. RESULTS: Incubation of intestinal tissues or LPMCs with otelixizumab reduced production of interferon gamma, interleukin (IL)-17A, and other inflammatory cytokines and chemokines, simultaneously increasing production of IL-10. Mucosal biopsy specimens from patients with IBD retained inflammation-associated tyrosine phosphoprotein profiles ex vivo. Incubation of the inflamed tissue with otelixizumab reduced phosphorylation of these proteins to levels observed in control tissues. Otelixizumab also markedly reduced phosphorylation of proteins associated with T-cell receptor activation. Neutralization of IL-10 blocked the anti-inflammatory effects of otelixizumab. CONCLUSIONS: We observed anti-inflammatory effects of anti-CD3 in inflamed intestinal tissues from patients with IBD. The antibody appears to down-regulate T-cell activation via IL-10.
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