BACKGROUND AND AIMS: Trefoil peptides (TFF1, TFF2 and TFF3) are acute phase proteins up-regulated in response to gastrointestinal mucosal damage. They promote cell migration, protect and heal the mucosa and may function as tumorsuppressors. We assumed them to be regulated by the proinflammatory cytokines interleukin-1beta (IL1beta) and interleukin-6 (IL6), which trigger the transcriptional factors NF-kappaB and C/EBPbeta. METHODS: Following IL1beta and IL6 stimulation, expression of TFF genes was analyzed in gastrointestinal cell lines HT-29 and KATO III by reporter gene assays using TFF promoter constructs and by quantitative real-time PCR. NF-kappaB and C/EBPbeta were transiently co-expressed. RESULTS: We have functionally identified transcription factors NF-kappaB and C/EBPbeta to inhibit transcription of human TFF genes. Down-regulation of TFF transcription is also observed by IL1beta and IL6, suggesting crosstalk with or in response to the immune system. IL1beta and IL6 caused a 3- to 11-fold reduction in TFF mRNA expression, displayed in real-time PCR. CONCLUSIONS: Down-regulation of intestinal trefoil factor TFF3 due to transcriptional repression by IL1beta through NF-kappaB as well as by IL6 through C/EBPbeta activation in vitro may reflect the situation in vivo and may contribute to ulceration and decreased wound healing during inflammatory bowel disease. Additionally, IL1 and IL6 over-expression in chronic gastritis may lead to mucosal damage and gastric carcinogenesis through transcriptional repression of TFF1 and TFF2. Copyright 2002 S. Karger AG, Basel
BACKGROUND AND AIMS: Trefoil peptides (TFF1, TFF2 and TFF3) are acute phase proteins up-regulated in response to gastrointestinal mucosal damage. They promote cell migration, protect and heal the mucosa and may function as tumorsuppressors. We assumed them to be regulated by the proinflammatory cytokines interleukin-1beta (IL1beta) and interleukin-6 (IL6), which trigger the transcriptional factors NF-kappaB and C/EBPbeta. METHODS: Following IL1beta and IL6 stimulation, expression of TFF genes was analyzed in gastrointestinal cell lines HT-29 and KATO III by reporter gene assays using TFF promoter constructs and by quantitative real-time PCR. NF-kappaB and C/EBPbeta were transiently co-expressed. RESULTS: We have functionally identified transcription factors NF-kappaB and C/EBPbeta to inhibit transcription of human TFF genes. Down-regulation of TFF transcription is also observed by IL1beta and IL6, suggesting crosstalk with or in response to the immune system. IL1beta and IL6 caused a 3- to 11-fold reduction in TFF mRNA expression, displayed in real-time PCR. CONCLUSIONS: Down-regulation of intestinal trefoil factor TFF3 due to transcriptional repression by IL1beta through NF-kappaB as well as by IL6 through C/EBPbeta activation in vitro may reflect the situation in vivo and may contribute to ulceration and decreased wound healing during inflammatory bowel disease. Additionally, IL1 and IL6 over-expression in chronic gastritis may lead to mucosal damage and gastric carcinogenesis through transcriptional repression of TFF1 and TFF2. Copyright 2002 S. Karger AG, Basel
Authors: Yan Yu; Hong Jin; Daniel Holder; Josef S Ozer; Stephanie Villarreal; Paul Shughrue; Shu Shi; David J Figueroa; Holly Clouse; Ming Su; Nagaraja Muniappa; Sean P Troth; Wendy Bailey; John Seng; Amy G Aslamkhan; Douglas Thudium; Frank D Sistare; David L Gerhold Journal: Nat Biotechnol Date: 2010-05 Impact factor: 54.908
Authors: George M H Birchenough; Malin E V Johansson; Richard A Stabler; Fatma Dalgakiran; Gunnar C Hansson; Brendan W Wren; J Paul Luzio; Peter W Taylor Journal: Infect Immun Date: 2013-06-24 Impact factor: 3.441
Authors: George P Christophi; Rong Rong; Philip G Holtzapple; Paul T Massa; Steve K Landas Journal: Inflamm Bowel Dis Date: 2012-03-29 Impact factor: 5.325
Authors: C Hernández; E Santamatilde; K J McCreath; A M Cervera; I Díez; D Ortiz-Masiá; N Martínez; S Calatayud; J V Esplugues; M D Barrachina Journal: Br J Pharmacol Date: 2008-12-09 Impact factor: 8.739
Authors: M B Loncar; E-d Al-azzeh; P S M Sommer; M Marinovic; K Schmehl; M Kruschewski; N Blin; R Stohwasser; P Gött; T Kayademir Journal: Gut Date: 2003-09 Impact factor: 23.059