Constitutive and cytokine induced expression of HLA molecules, secretory component, and intercellular adhesion molecule-1 is modulated by butyrate in the colonic epithelial cell line HT-29.

Kvale, Dag; Brandtzæg, Per

doi:10.1136/gut.36.5.737

Cited by 78 publications

(40 citation statements)

References 20 publications

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“…Such cytokine-mediated up-regulation of pIgR is known to depend on de novo protein synthesis (8 -11), and has recently been shown to take place at the level of transcription in which IL-4 had the greatest effect on the transcription rate of the tested cytokines (10). This effect of IL-4 has been observed both in a human lung carcinoma cell line, Calu-3 (11,12), and in a human colonic carcinoma cell line, HT-29 (13,14). Furthermore, IL-4-mediated up-regulation of pIgR is known to be sensitive to inhibitors of tyrosine phosphorylation, indicating a signaling pathway dependent on protein tyrosine phosphorylation (11,15).…”

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confidence: 96%

Mechanism of IL-4-Mediated Up-Regulation of the Polymeric Ig Receptor: Role of STAT6 in Cell Type-Specific Delayed Transcriptional Response

Schjerven

Brandtzæg

Johansen

2000

The Journal of Immunology

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The polymeric IgR (pIgR) mediates transport of dimeric IgA and pentameric IgM across mucosal epithelia, thereby generating secretory Abs. Its expression is up-regulated at the transcriptional level by IL-4 in HT-29 cells. In this study, we demonstrate that IL-4 mediates up-regulation of human pIgR through a 554-bp IL-4-responsive enhancer in intron 1. Mutation of a binding site for STAT-6 within this region abolished IL-4-induced enhancement, while an adjacent putative C/EBP site was dispensable. IL-4 treatment induced binding of STAT6 to the intronic STAT6 site, but cooperation with nearby upstream and downstream DNA elements was required for IL-4 responsiveness. Furthermore, IL-4-mediated increased transcription of the pIgR-derived enhancer, like the endogenous pIgR gene, required de novo protein synthesis. Interestingly, a conditionally active form of STAT6 sufficed to activate a pIgR-derived enhancer in HT-29 cells, but not in Cos-1 cells, suggesting a requirement for cell type-specific factors. Thus, STAT6 activation mediates a delayed transcriptional enhancement of pIgR by induction of a de novo synthesized protein that cooperates with STAT6 itself bound to its cognate DNA element in intron 1. This mechanism may represent a general strategy for how pleiotropic cytokines elicit cell type-specific transcriptional responses.

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confidence: 96%

Mechanism of IL-4-Mediated Up-Regulation of the Polymeric Ig Receptor: Role of STAT6 in Cell Type-Specific Delayed Transcriptional Response

Schjerven

Brandtzæg

Johansen

2000

The Journal of Immunology

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“…Evidence suggests that SCFAs, particularly butyrate, serve as the principal metabolic fuel for colonic epithelial cells and exert a variety of effects fundamental to the health of normal colonic mucosa (47). For example, butyrate plays an essential role in suppressing mucosal inflammation (26,34) and exhibits antitumorigenic effects such as induction of cell cycle arrest, differentiation, and apoptosis (20,23,40,57). Butyrate is also known to stimulate colonic electroneutral NaCl absorption and to inhibit Cl Ϫ secretion (2,45).…”

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confidence: 99%

PKC-dependent stimulation of the human MCT1 promoter involves transcription factor AP2

Saksena¹,

Dwivedi²,

Gill³

et al. 2009

American Journal of Physiology-Gastrointestinal and Liver Physi

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Saksena S, Dwivedi A, Gill RK, Singla A, Alrefai WA, Malakooti J, Ramaswamy K, Dudeja PK. PKC-dependent stimulation of the human MCT1 promoter involves transcription factor AP2. Am J Physiol Gastrointest Liver Physiol 296: G275-G283, 2009. First published November 25, 2008 doi:10.1152/ajpgi.90503.2008.-Monocarboxylate transporter (MCT1) plays an important role in the absorption of short-chain fatty acids (SCFA) such as butyrate in the human colon. Previous studies from our laboratory have demonstrated that phorbol ester, PMA (1 M, 24 h), upregulates butyrate transport and MCT1 protein expression in human intestinal Caco-2 cells. However, the molecular mechanisms involved in the transcriptional regulation of MCT1 gene expression by PMA in the intestine are not known. In the present study, we showed that PMA (0.1 M, 24 h) increased the MCT1 promoter activity (Ϫ871/ϩ91) by approximately fourfold. A corresponding increase in MCT1 mRNA abundance in response to PMA was also observed. PMA-induced stimulation of MCT1 promoter activity was observed as early as 1 h and persisted until 24 h, suggesting that the effects of PMA are attributable to initial PKC activation. Kinase inhibitor and phosphorylation studies indicated that these effects may be mediated through activation of the atypical PKC-isoform. 5Ј-deletion studies demonstrated that the MCT1 core promoter region (Ϫ229/ϩ91) is the PMA-responsive region. Site-directed mutagenesis studies showed the predominant involvement of potential activator protein 2 (AP2) binding site in the activation of MCT1 promoter activity by PMA. In addition, overexpression of AP2 in Caco-2 cells significantly increased MCT1 promoter activity in a dose-dependent manner. These findings showing the regulation of MCT1 promoter by PKC and AP2 are of significant importance for an understanding of the molecular regulation of SCFA absorption in the human intestine.short-chain fatty acid absorption; transcriptional regulation; human intestine; protein kinase C-; activator protein 2 MONOCARBOXYLATE TRANSPORTER 1 (MCT1) is a member of the solute carrier family1 of MCTs known to mediate the transport of monocarboxylates such as lactate and pyruvate (21, 46) and a wide range of short-chain fatty acids (SCFAs), e.g., acetate, propionate, and butyrate, across the plasma membrane of a variety of cell types (17,22,32). In humans, at least 14 MCT isoforms have been identified, but only MCT1-MCT4 have been structurally and functionally well characterized (21). Evidence suggests that SCFAs, particularly butyrate, serve as the principal metabolic fuel for colonic epithelial cells and exert a variety of effects fundamental to the health of normal colonic mucosa (47). For example, butyrate plays an essential role in suppressing mucosal inflammation (26, 34) and exhibits antitumorigenic effects such as induction of cell cycle arrest, differentiation, and apoptosis (20,23,40,57). Butyrate is also known to stimulate colonic electroneutral NaCl absorption and to inhibit Cl Ϫ secretion (2, 45). Although much is kn...

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“…It has recently been reported that infection with reovirus up-regulates expression of pIgR in the human intestinal epithelial cell-line HT29 (18). Butyrate, a bacterial fermentation product and important energy source in the colon, has also been shown to up-regulate pIgR expression in HT29 cells (19). A role for commensal bacteria in pIgR regulation was suggested by the observation that intestinal pIgR mRNA levels were up-regulated when germfree mice were colonized with Bacteroides thetaiotaomicron, a prominent bacterium of the intestinal flora (20).…”

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confidence: 99%

Regulation of the Polymeric Ig Receptor by Signaling through TLRs 3 and 4: Linking Innate and Adaptive Immune Responses

Schneeman¹,

Bruno²,

Schjerven

et al. 2005

The Journal of Immunology

104

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IgA Abs help to maintain homeostasis at mucosal surfaces by promoting defense mechanisms that protect against pathogens while suppressing inflammatory responses to commensal organisms and food Ags. The polymeric Ig receptor (pIgR) mediates transport of IgA across mucosal epithelial cells. We hypothesized that signaling through TLRs may up-regulate pIgR expression by intestinal epithelial cells and thus enhance IgA-mediated homeostasis. To test this hypothesis we treated the HT29 human intestinal epithelial cell line with dsRNA, a ligand for TLR3, or LPS, a ligand for TLR4. Both dsRNA and LPS up-regulated levels of pIgR mRNA and cell surface pIgR protein. By contrast, dsRNA but not LPS up-regulated expression of TLR3 and TLR4 mRNA. However, cell surface expression of both TLR3 and TLR4 was enhanced by treatment of HT29 cells with their respective ligands. Transfection of HT29 cells with wild-type and mutated promoter/enhancer plasmids suggested that TLR3 and TLR4 signal primarily through NF-κB to enhance transcription of pIgR mRNA. TLR3 signaling resulted in a more pronounced inflammatory response than did TLR4, as evidenced by up-regulation of the transcription factor IFN regulatory factor-1, chemokines IL-8 and RANTES, and the proinflammatory cytokine TNF. Signaling through LPS/TLR4 appears to up-regulate pIgR expression while minimizing proinflammatory responses, a mechanism that could promote IgA-mediated homeostasis in the presence of commensal Gram-negative bacteria.

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Constitutive and cytokine induced expression of HLA molecules, secretory component, and intercellular adhesion molecule-1 is modulated by butyrate in the colonic epithelial cell line HT-29.

Abstract: (Gut 1995; 36: 737-742)

Cited by 78 publications

References 20 publications

Mechanism of IL-4-Mediated Up-Regulation of the Polymeric Ig Receptor: Role of STAT6 in Cell Type-Specific Delayed Transcriptional Response

Mechanism of IL-4-Mediated Up-Regulation of the Polymeric Ig Receptor: Role of STAT6 in Cell Type-Specific Delayed Transcriptional Response

PKC-dependent stimulation of the human MCT1 promoter involves transcription factor AP2

Regulation of the Polymeric Ig Receptor by Signaling through TLRs 3 and 4: Linking Innate and Adaptive Immune Responses

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