Activation pattern of signal transducers and activators of transcription (STAT) factors in inflammatory bowel diseases

Détails

ID Serval
serval:BIB_2411DABCEC57
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Activation pattern of signal transducers and activators of transcription (STAT) factors in inflammatory bowel diseases
Périodique
American Journal of Gastroenterology
Auteur(s)
Mudter  J., Weigmann  B., Bartsch  B., Kiesslich  R., Strand  D., Galle  P. R., Lehr  H. A., Schmidt  J., Neurath  M. F.
ISSN
0002-9270 (Print)
Statut éditorial
Publié
Date de publication
2005
Volume
100
Numéro
1
Pages
64-72
Notes
PT - Journal Article PT - Research Support, Non-U.S. Gov't
Résumé
OBJECTIVES: Cytokine signaling pathways involving transcription factors of the signal transducers and activators of transcription (STAT) family play a key role in the pathogenesis of inflammatory bowel diseases (IBD). STAT proteins are latent cytoplasmic transcription factors that induce transcription upon phosphorylation, dimerization, and nuclear translocation. However, their activation pattern in IBD is poorly understood. The aim of our study was to characterize STAT-expression in IBD. METHODS: Mononuclear cells were isolated from 36 colonic specimens of Crohn's disease, ulcerative colitis, or from control patients. Cells were stimulated overnight with antibodies against human CD2 and CD28 and mononuclear cells were analyzed by flow cytometry. Alternatively, CD4(+) T cells were immunomagnetically separated and then assessed by flow cytometry. Intracellular stainings of the following transcription factors were performed: STAT-1, STAT-2, STAT-3, STAT-4, and STAT-6. In addition, immunofluorescence staining on cryosections for phosphorylated STAT-1 and STAT-3 was performed. RESULTS: Average expression of the IFN-gamma inducible transcription factor STAT-1 was increased in Crohn's disease as compared to patients with ulcerative colitis and control patients. However, levels of phospho-STAT-1 were surprisingly not markedly upregulated in IBD as compared to controls. In contrast, STAT-3 and phospho-STAT-3 levels were significantly increased in IBD patients as compared to controls (p < 0.01). No differences could be detected in STAT-6 levels. Finally, average expression of STAT-2, which is involved in type I interferon signalling, was downregulated in IBD as compared to control patients. CONCLUSIONS: The analysis of STAT activation patterns could serve as a helpful tool to characterize intestinal inflammation. Furthermore, the IL-6/STAT-3 rather than the IFN-gamma/STAT-1 signaling pathway emerges as a key target for the development of future therapeutic concepts in IBD
Mots-clé
CD4-Positive T-Lymphocytes/metabolism/Case-Control Studies/Colon/Pathology/DNA-Binding Proteins/Humans/Inflammatory Bowel Diseases/STAT1 Transcription Factor/STAT2 Transcription Factor/STAT3 Transcription Factor/STAT4 Transcription Factor/STAT6 Transcription Factor/Trans-Activators
Pubmed
Web of science
Création de la notice
29/01/2008 19:33
Dernière modification de la notice
03/03/2018 14:56
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