Tumour necrosis factor   and nuclear factor  B inhibit transcription of human TFF3 encoding a gastrointestinal healing peptide

Lončar, Mirela Baus

doi:10.1136/gut.52.9.1297

Cited by 64 publications

(52 citation statements)

References 61 publications

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“…First, there are a number of growth factors and cytokines, such as TNF-␣, TGF-␤, and HGF that contribute to BEC pathophysiology after BDL, 6,48 -50 but are not produced primarily by BECs or differentially regulated in vitro under the conditions used in this study. However, we and others have shown that TNF-␣, 21 TGF-␤, and HGF can down-regulate BEC TFF3 expression. Thus, additional factors present in vivo, but not in vitro, significantly influence BEC TFF3 expression.…”

Section: Discussionmentioning

confidence: 99%

“…6 TNF-␣ has already been shown to decrease TFF3 expression. 21 These growth factors and cytokines are important in intestinal epithelial wound healing, but are not produced or differentially regulated by BEC cultures in C-SFM. 13 The results show that HGF and TGF-␤ significantly decrease BEC TFF3 mRNA and protein expression in a concentration-dependent manner Figure 4, D and E.…”

Section: Mapk Signaling Decreases Bec Tff3 Expression Whereas Stat3 Imentioning

confidence: 99%

“…6,19,20 Examples include TNF-␣, HGF, and TGF-␤, which are not produced or differentially regulated by BECs under this condition (data not shown), but can significantly decrease TFF3 expression. 21 Finally however, the dynamic regulation of TFF3 mRNA and protein expression was studied in relationship to STAT3 and MAPK signaling, in vivo, using a chronic BDL model in IL-6 ϩ/ϩ and IL-6 Ϫ/Ϫ mice. The purpose of the in vitro studies was to determine the relative contribution of IL-6 signaling pathways to BEC TFF3 expression, in vivo, under real disease conditions.…”

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confidence: 99%

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Regulation and Function of Trefoil Factor Family 3 Expression in the Biliary Tree

Nozaki

Lunz

Specht

et al. 2004

The American Journal of Pathology

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Microarray analysis identified trefoil factor family 3 (TFF3) as a gene expressed in biliary epithelial cells (BECs), regulated by interleukin (IL)-6, and potentially involved in biliary pathophysiology. We therefore studied the regulation and function of BEC TFF3, in vitro and in vivo in IL-6 ؉/؉ and IL-6 ؊/؊ mice subjected to chronic bile duct ligation for 12 weeks. In vitro studies showed that IL-6 wild-type (IL-6 ؉/؉ ) BECs expressed higher TFF3 mRNA and protein levels than IL-6-deficient (IL-6 ؊/؊ ) BECs. BEC TFF3 expression is dependent primarily on signal transducer and activator of transcription (STAT3) signaling, but the reciprocal negative regulation known to exist between the intracellular IL-6/gp130 signaling pathways, STAT3 and mitogen-activated protein kinase (MAPK), importantly contributes to BEC TFF3 expression. Specifically blocking STAT3 activity with a dominant-negative molecule or treatment with a growth factor such as hepatocyte growth factor, which increases MAPK signaling, decreases BEC TFF3 expression. In contrast, specifically blocking MAPK activity with PD98059 significantly increased BEC TFF3 expression. Higher BEC TFF3 levels in IL-6 ؉/؉ BECs were associated with significantly better migration than IL-6 ؊/؊ BECs in a wound-healing assay and defective IL-6 ؊/؊ BEC migration was reversed with exogenous TFF3. In vivo, hepatic TFF3 mRNA and protein expression was limited to BECs and dependent significantly on STAT3 signaling, but was influenced by other factors present after bile duct ligation. Com-

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Section: Discussionmentioning

confidence: 99%

Section: Mapk Signaling Decreases Bec Tff3 Expression Whereas Stat3 Imentioning

confidence: 99%

mentioning

confidence: 99%

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Regulation and Function of Trefoil Factor Family 3 Expression in the Biliary Tree

Nozaki

Lunz

Specht

et al. 2004

The American Journal of Pathology

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“…The NF-κB is an inducible transcription factor that mediates the signal transduction between the nucleus and the cytoplasm in a number of cell types and controls the expression of many genes involved in cell growth, differentiation, apoptosis regulation, cytokine production, and neoplastic transformation (21). In mammals, the NF-κB is made up of fi ve different elements: RelA (p65), RelB, cRel (Rel), NF-κB1 (p50 as a precursor p105) and NF-κB2 (p52 as a precursor p100).…”

Section: Discussionmentioning

confidence: 99%

Chemopreventive potential of alpha lipoic acid in the treatment of colon and cervix cancer cell lines

Damnjanović¹,

Kocić²,

Najman³

et al. 2014

BLL

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Abstract:Objectives: The nuclear factor κB regulates the expression of genes involved in many processes that play a key role in the development and progression of cancer. The aim of this study was to examine the infl uence of the alpha lipoic acid in the chemoprevention of colon and cervix carcinoma in vitro. Background: In recent years, special attention has been paid to the potential chemopreventive properties of antioxidants. There are no published data on the impact of alpha lipoc acid of chemoprevention of cervix and colon cancer. Methods: We examined the effect of alpha lipoic acid alone or in combination with cisplatin and 5-fl uorouracil on proliferation of the two cell lines, HeLa (human cervical carcinoma cells) and Caco-2 (human colon cancer cells) by MTT test. The measurement of the level of transcription factor NF-κB was also performed in the cells of both cell lines. Results: At least one of the mechanisms of the antiproliferative and/or cytotoxic effect of alpha lipoic acid on Caco-2 and HeLa cells at high concentrations, the transcription factor NF-κB, may be involved, as well as the products of transcription of genes that are under its control. Conclusion: The alpha lipoic acid has proven to be a promising candidate in the combat arena against cancer (Tab. 4, Ref. 31). Text in PDF www.elis.sk.

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“…The expression of all TFF subtypes was significantly repressed by this forced overexpression, which suggests that inflammatory responses in the gastric mucosa lead to the downregulation of TFF expression. The most significant suppressive effect exerted by proinflammatory cytokines was on TFF3 expression, 31,32 and the alteration of TFF1 expression in response to IL1-b or TNF-a was not so significant in gastric cell lines. Given this situation, it would be interesting to know the effect of Helicobacter pylori infection on the expression of TFF1.…”

mentioning

confidence: 99%

Review article: regulation of TFF1 (pS2) expression in gastric epithelial cells

Fujii

Shimada

Koike

et al. 2006

Aliment Pharmacol Ther

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SUMMARYTrefoil factor family (TFF) is a group of small peptides secreted by gastrointestinal epithelial cells.Among three known TFF peptides, TFF1 (formerly pS2) is expressed at a high level in gastric epithelial cells and plays an essential and critical role in maintaining the integrity of the gastric mucosa. Recent evidence also suggests that TFF1 acts as a tumour suppressor gene in the stomach.TFF1 was originally discovered as an oestrogen-inducible gene in MCF-7 breast cancer cells, and its expression is dependent on oestrogen in MCF-7 and other hormone-dependent breast cancer cells. Although gastric epithelial cells express oestrogen receptors (ERs), gastric TFF1 expression appears to be independent of oestrogen signalling. Instead, several cis-regulatory elements are involved in the regulation of gastric TFF1 expression and balanced signalling from gp130, a common IL-6 family coreceptor, has been shown to be necessary for the proper expression of TFF1 in the stomach.Epigenetic regulation, such as DNA methylation in the promoter region of the TFF1 gene, may be also important for tissue-specific expression of TFF1 in the stomach. However, further studies are still needed to fully understand the detailed regulatory mechanisms of TFF1 expression in gastric epithelial cells.

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Tumour necrosis factor and nuclear factor B inhibit transcription of human TFF3 encoding a gastrointestinal healing peptide

Cited by 64 publications

References 61 publications

Regulation and Function of Trefoil Factor Family 3 Expression in the Biliary Tree

Regulation and Function of Trefoil Factor Family 3 Expression in the Biliary Tree

Chemopreventive potential of alpha lipoic acid in the treatment of colon and cervix cancer cell lines

Review article: regulation of TFF1 (pS2) expression in gastric epithelial cells

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