DNA Methylation and Transcription Patterns in Intestinal Epithelial Cells From Pediatric Patients With Inflammatory Bowel Diseases Differentiate Disease Subtypes and Associate With Outcome

Intestinal epithelial cells cover the surface of the intestinal tract. The cells are important for preserving the integrity of the mucosal barriers to protect the host from luminal antigens and pathogens. The mucosal barriers are maintained by the continuous and rapid self-renewal of intestinal epithelial cells. Defects in the self-renewal of these cells are associated with gastrointestinal diseases, including inflammatory bowel diseases and diarrhea. Zinc is an essential trace element for living organisms, and zinc deficiency is closely linked to the impaired mucosal integrity. Recent evidence has shown that zinc transporters contribute to the barrier function of intestinal epithelial cells. In this review, we describe the recent advances in understanding the role of zinc and zinc transporters in the barrier function and homeostasis of intestinal epithelial cells.

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Proteomic analysis of cytokine induced proteins in human intestinal epithelial cells: Implications for inflammatory bowel diseases

PROTEOMICS ◽

10.1002/1615-9861(200205)2:5<551::aid-prot551>3.0.co;2-o ◽

2002 ◽

Vol 2 (5) ◽

pp. 551-560 ◽

Cited By ~ 79

Author(s):

Sílvia Barceló-Batllori ◽

Muriel André ◽

Catherine Servis ◽

Nicole Lévy ◽

Osamu Takikawa ◽

...

Keyword(s):

Epithelial Cells ◽

Inflammatory Bowel Diseases ◽

Proteomic Analysis ◽

Intestinal Epithelial Cells ◽

Intestinal Epithelial ◽

Human Intestinal Epithelial Cells ◽

Bowel Diseases ◽

Inflammatory Bowel ◽

Induced Proteins

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Signaling pathway via TNF-α/NF-κB in intestinal epithelial cells may be directly involved in colitis-associated carcinogenesis

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00071.2008 ◽

2009 ◽

Vol 296 (4) ◽

pp. G850-G859 ◽

Cited By ~ 87

Author(s):

Michio Onizawa ◽

Takashi Nagaishi ◽

Takanori Kanai ◽

Ken-ichi Nagano ◽

Shigeru Oshima ◽

...

Keyword(s):

Epithelial Cells ◽

Maintenance Therapy ◽

Intestinal Epithelial Cells ◽

Immunoblot Analysis ◽

Intestinal Epithelial ◽

Tnf Receptor ◽

Tnf Α ◽

Sequential Administration ◽

Bowel Diseases ◽

Inflammatory Bowel

Treatment with anti-TNF-α MAb has been accepted as a successful maintenance therapy for patients with inflammatory bowel diseases (IBD). Moreover, it has been recently reported that blockade of TNF receptor (TNFR) 1 signaling in infiltrating hematopoietic cells may prevent the development of colitis-associated cancer (CAC). However, it remains unclear whether the TNF-α signaling in epithelial cells is involved in the development of CAC. To investigate this, we studied the effects of anti-TNF-α MAb in an animal model of CAC by administration of azoxymethane (AOM) followed by sequential dextran sodium sulfate (DSS) ingestion. We observed that the NF-κB pathway is activated in colonic epithelia from DSS-administered mice in association with upregulation of TNFR2 rather than TNFR1. Immunoblot analysis also revealed that the TNFR2 upregulation accompanied by the NF-κB activation is further complicated in CAC tissues induced in AOM/DSS-administered mice compared with the nontumor area. Such NF-κB activity in the epithelial cells is significantly suppressed by the treatment of MP6-XT22, an anti-TNF-α MAb. Despite inability to reduce the severity of colitis, sequential administration of MP6-XT22 reduced the numbers and size of tumors in association with the NF-κB inactivation. Taken together, present studies suggest that the TNFR2 signaling in intestinal epithelial cells may be directly involved in the development of CAC with persistent colitis and imply that the maintenance therapy with anti-TNF-α MAb may prevent the development of CAC in patients with long-standing IBD.

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Inflammatory bowel diseases influence major histocompatibility complex class I (MHC I) and II compartments in intestinal epithelial cells

Clinical & Experimental Immunology ◽

10.1111/cei.12047 ◽

2013 ◽

Vol 172 (2) ◽

pp. 280-289 ◽

Cited By ~ 9

Author(s):

F. Bär ◽

C. Sina ◽

G. Hundorfean ◽

R. Pagel ◽

H. Lehnert ◽

...

Keyword(s):

Major Histocompatibility Complex ◽

Inflammatory Bowel Diseases ◽

Intestinal Epithelial Cells ◽

Intestinal Epithelial ◽

Complex Class ◽

Class I Mhc ◽

Mhc I ◽

Histocompatibility Complex ◽

Bowel Diseases ◽

Inflammatory Bowel

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The DNA Methylome of Inflammatory Bowel Disease (IBD) reflects intrinsic and extrinsic factors in intestinal epithelial cells

10.1101/565200 ◽

2019 ◽

Author(s):

Iolanda Agliata ◽

Nora Fernandez-Jimenez ◽

Chloe Goldsmith ◽

Julien C. Marie ◽

Jose Ramon Bilbao ◽

...

Keyword(s):

Dna Methylation ◽

Inflammatory Bowel Disease ◽

Epithelial Cells ◽

Bowel Disease ◽

Intestinal Epithelial Cells ◽

Meta Analysis ◽

Intestinal Epithelial ◽

Extrinsic Factors ◽

Environmental Signals ◽

Inflammatory Bowel

AbstractAbnormal DNA methylation has been described in human inflammatory conditions of the gastrointestinal tract, such as inflammatory bowel disease (IBD). As other complex diseases, IBD results from the balance between genetic predisposition and environmental exposures. As such, DNA methylation may be placed as an effector of both, genetic susceptibility variants and/or environmental signals such as cytokine exposure. We attempted to discern between these two non-excluding possibilities by performing a meta-analysis of DNA methylation data in intestinal epithelial cells of IBD and control samples. We identified abnormal DNA methylation at different levels: deviation from mean methylation signals at site and region levels, and differential variability. A fraction of such changes are associated with genetic polymorphisms linked to IBD susceptibility. In addition, by comparing with another intestinal inflammatory condition (i.e. celiac disease) we propose that aberrant DNA methylation can also be the result of unspecific processes such as chronic inflammation. Our characterization suggests that IBD methylomes combine intrinsic and extrinsic responses in intestinal epithelial cells, and could point to knowledge-based biomarkers of IBD detection and progression.Graphical AbstractConceptual representation of the study. Using a meta-analysis strategy we identified differentially methylated positions or regions (DMP/DMR) in IBD. Our assumption is that gene expression changes (IBD phenotype) take place downstream of DNA methylation. In turn, abnormal DNA methylation can be explained by a direct effect of inflammatory cytokines (“signaling”) and/or the result of a genetic polymorphism (SNP). SNP-DMP associations are called methylation quantitative trait loci (mQTL).

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Toll-like receptors 2 and 4 modulate intestinal IL-10 differently in ileum and colon

United European Gastroenterology Journal ◽

10.1177/2050640617727180 ◽

2017 ◽

Vol 6 (3) ◽

pp. 446-453 ◽

Cited By ~ 7

Author(s):

Eva Latorre ◽

Elena Layunta ◽

Laura Grasa ◽

Julián Pardo ◽

Santiago García ◽

...

Keyword(s):

Epithelial Cells ◽

Intestinal Epithelial Cells ◽

Cell Model ◽

Immune Recognition ◽

Intestinal Epithelial ◽

Intestinal Homeostasis ◽

Bowel Diseases ◽

Inflammatory Bowel ◽

Gram Negative Organisms ◽

Tlr4 Activation

Background Inflammatory bowel diseases are consequence of an intestinal homeostasis breakdown in which innate immune dysregulation is implicated. Toll-like receptor (TLR)2 and TLR4 are immune recognition receptors expressed in the intestinal epithelium, the first physical-physiological barrier for microorganisms, to inform the host of the presence of Gram-positive and Gram-negative organisms. Interleukin (IL)-10 is an essential anti-inflammatory cytokine that contributes to maintenance of intestinal homeostasis. Aim Our main aim was to investigate intestinal IL-10 synthesis and release, and whether TLR2 and TLR4 are determinants of IL-10 expression in the intestinal tract. Methods We used Caco-2 cell line as an enterocyte-like cell model, and also ileum and colon from mice deficient in TLR2, TLR4 or TLR2/4 to test the involvement of TLR signaling. Results Intestinal epithelial cells are able to synthesize and release IL-10 and their expression is increased after TLR2 or TLR4 activation. IL-10 regulation seems to be tissue specific, with IL-10 expression in the ileum regulated by a compensation between TLR2 and TLR4 expression, whereas in the colon, TLR2 and TLR4 affect IL-10 expression independently. Conclusions Intestinal epithelial cells could release IL-10 in response to TLR activation, playing an intestinal tissue-dependent and critical intestinal immune role.

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