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RESEARCH PRODUCT
Activation pattern of signal transducers and activators of transcription (STAT) factors in inflammatory bowel diseases.
Peter R. GalleBrigitte BartschJan SchmidtJonas MudterRalf KiesslichHans A. LehrDennis StrandMarkus F. NeurathBenno Weigmannsubject
CD4-Positive T-LymphocytesSTAT3 Transcription FactorColonActivation patternstatTranscription (biology)MedicineHumansSTAT4Transcription factorHepatologybusiness.industryActivator (genetics)digestive oral and skin physiologyGastroenterologySTAT2 Transcription FactorSTAT3 Transcription FactorSTAT4 Transcription FactorInflammatory Bowel Diseasesdigestive system diseasesDNA-Binding ProteinsSTAT1 Transcription FactorCase-Control StudiesImmunologyCancer researchTrans-ActivatorsSignal transductionbusinessSTAT6 Transcription Factordescription
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.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.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 (p0.01). 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.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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2005-01-19 | The American journal of gastroenterology |