Naslov
TNF-α and NFκB inhibit transcription of human TFF genes encoding gastro-intestinal healing peptides
(TNF-α and NFκ B inhibit transcription of human TFF genes encoding gastro-intestinal healing peptides)

Autori
Baus Lončar, Mirela ; Sommer, P. ; Al-Azzeh, E. ; Blin, N. ; Marinović, M. ; Schmehl, K. ; Kruschewski, M. ; Stohwasser, R. ; Gött, P.

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Annual meeting of the German Genetics Society : Book of abstracts / - , 2001

Skup
Annual meeting of the German Genetics Society

Mjesto i datum
Halle, Njemačka, 04.10.2001. - 06.10.2001

Vrsta sudjelovanja
Poster

Vrsta recenzije
Nije recenziran

Ključne riječi
TNF-α stimulation; NF-κ B transcription factor; gene regulation; HT-29 and Kato III cell lines

Sažetak
Damage to the gastrointestinal mucosa results in an up-regulation of the trefoil factor family peptides TFF1, TFF2 and TFF3 connected with protective, curative and tumor suppressive functions. We suspected TFF genes to be regulated by the proinflammatory cytokine TNF-α via transcription factor NF-κ B. After TNF-α stimulation, expression of TFF genes was analyzed by quantitative real-time RT-PCR and by reporter gene assays using wild type and mutated TFF promotors in gastrointestinal cell lines HT-29 and KATO III. NF-κ B and a constitutive repressive form of Iκ B were transiently co-expressed. NF-κ B binding was tested by electrophoretic mobility shift assays. In vivo, morphological changes, expression of TFF3, mucins and NF-κ B was monitored by immunohistochemistry in a rat model of TNBS-induced colitis. TNF-α stimulation evoked a 3-4 fold reduced TFF2 expression and an up to 20-fold reduction of TFF3 expression. Down-regulation of reporter gene transcription of all three TFF genes was observed by both TNF-α and NF-κ B, and was reversible by Iκ B. Some of the putative NF-κ B binding sites in the 5’ -flanking region of TFFs were shown to function as silencers. In vivo, epithelial NF-κ B expression coincided with strongly reduced TFF3 expression during acute phase of experimental colitis. Therefore, down-regulation of intestinal trefoil factor TFF3 caused by transcriptional repression through TNF-α and NF-κ B activation in vitro reflects the situation in inflammatory bowel disease and may contribute to ulceration and decreased wound healing

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

Napomena
Rad je kao poster prezentiran i na skupu Trefoils & Mucins, održanom od 02.-04.04.2002., Oxford, Velika Britanija ; objavljen u Knjizi sažetaka.

POVEZANOST RADA