Tumour necrosis factor α and nuclear factor κB inhibit transcription of human TFF3 encoding a gastrointestinal healing peptide
| Autor: | M. Kruschewski, K. Schmehl, M. B. Loncar, M. Marinovic, Patricia Sommer, Ezzal-din Al-azzeh, R. Stohwasser, Tuncay Kayademir, P. Gött, N. Blin |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2003 |
| Předmět: |
medicine.medical_specialty
Down-Regulation Biology Polymerase Chain Reaction Downregulation and upregulation In vivo Genes Reporter Internal medicine medicine Tumor Cells Cultured Animals Humans education Luciferases Regulation of gene expression Reporter gene education.field_of_study Trefoil factor 3 Tumor Necrosis Factor-alpha Inflammatory Bowel Disease Neuropeptides Gastroenterology Trefoil factor 2 NF-kappa B NFKB1 Colitis Rats Endocrinology Gene Expression Regulation Models Animal Cancer research Tumor necrosis factor alpha Trefoil Factor-2 TNF-alpha NF-kappaB TFF3 gene Trefoil Factor-3 HT29 Cells |
| Popis: | and aims: Tumour necrosis factor alpha (TNF-alpha) induction of nuclear factor kappaB (NFkappaB) activation plays a major role in the pathogenesis of inflammatory bowel disease (IBD). Trefoil factor family peptides TFF1, TFF2, and TFF3 exert protective, curative, and tumour suppressive functions in the gastrointestinal tract. In this study, we investigated effects of the TNF-alpha/NFkappaB regulatory pathway by TNF-alpha on expression of TFFs.After TNF-alpha stimulation, expression of TFF genes was analysed by quantitative real time polymerase chain reaction and by reporter gene assays in the gastrointestinal tumour cell lines HT-29 and KATO III. Additionally, NFkappaB subunits and a constitutive repressive form of inhibitory factor kappaB (IkappaB) were transiently coexpressed. In vivo, morphological changes and expression of TFF3, mucins, and NFkappaB were monitored by immunohistochemistry in a rat model of 2,4,6-trinitrobenzene sulphonic acid induced colitis.TNF-alpha stimulation evoked up to 10-fold reduction of TFF3 expression in the colon tumour cell line HT-29. Downregulation of reporter gene transcription of TFF3 was observed with both TNF-alpha and NFkappaB, and was reversible by IkappaB. In vivo, the increase in epithelial expression of NFkappaB coincided with reduced TFF3 expression during the acute phase of experimental colitis.Downregulation of intestinal trefoil factor TFF3 is caused by repression of transcription through TNF-alpha and NFkappaB activation in vitro. In IBD, perpetual activation of NFkappaB activity may contribute to ulceration and decreased wound healing through reduced TFF3. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|