scholarly journals Giardia lamblia-Induced Changes in Gene Expression in Differentiated Caco-2 Human Intestinal Epithelial Cells

2005 ◽  
Vol 73 (12) ◽  
pp. 8204-8208 ◽  
Author(s):  
Katarina Roxström-Lindquist ◽  
Emma Ringqvist ◽  
Daniel Palm ◽  
Staffan Svärd
Keyword(s):  
Intestinal Epithelium ◽  
Giardia Lamblia ◽  
Intestinal Inflammation ◽  
Expression Patterns ◽  
Enteric Pathogens ◽  
Intestinal Cells ◽  
Intestinal Epithelial ◽  
Innate And Adaptive Immunity ◽  
Human Intestinal Epithelial Cells ◽  
Induced Changes

ABSTRACT The parasitic protozoan Giardia lamblia is a worldwide cause of diarrhea, but the mechanism of disease remains elusive. The parasite colonizes the small intestinal epithelium, known to be a sensor for the presence of enteric pathogens, without invading or causing severe inflammation. In this study we investigated the epithelial cell response to G. lamblia. Differentiated Caco-2 cells were infected with G. lamblia isolate WB-A11, and the transcriptome of the intestinal cells was analyzed after 1.5, 6, and 18 h of interaction, using oligonucleotide microarrays. A large number of genes displayed changed expression patterns, showing the complexity of the interaction between G. lamblia and intestinal cells. A novel chemokine profile (CCL2, CCL20, CXCL1, CXCL2, and CXCL3) was induced that was different from the response induced by enteric pathogens causing intestinal inflammation. Several genes involved in stress regulation changed their expression. These findings indicate that the intestinal epithelium senses the G. lamblia infection, and this is important for induction of innate and adaptive immunity. The induced stress response can be important in the pathogenesis.

scholarly journals Crosstalk Between Nuclear Glucose-Regulated Protein 78 and Tumor Protein 53 Contributes to the Lipopolysaccharide Aggravated Apoptosis of Endoplasmic Reticulum Stress-Responsive Porcine Intestinal Epithelial Cells

2018 ◽  
Vol 48 (6) ◽  
pp. 2441-2455 ◽  
Author(s):  
Qian Jiang ◽  
Gang Liu ◽  
Jiashun Chen ◽  
Kang Yao ◽  
Yulong Yin
Keyword(s):  
Endoplasmic Reticulum ◽  
Epithelial Cells ◽  
Endoplasmic Reticulum Stress ◽  
Intestinal Inflammation ◽  
Intestinal Epithelial Cells ◽  
Intestinal Cells ◽  
Intestinal Epithelial ◽  
Gram Negative ◽  
Rna Transfection ◽  
Glucose Regulated Protein

Background/Aims: Lipopolysaccharides (LPSs) act as virulence factors that trigger intestinal inflammation and thereby compromise the production of pigs worldwide. Intestinal diseases and dysfunction have been attributed to endoplasmic reticulum stress (ERS) and the subsequent apoptosis of intestinal epithelial cells. Therefore It is important to explore whether LPSs aggravate ERS-mediated apoptosis of intestinal epithelial cells. Methods: ERS and inflammation models were established in porcine cell line J2 (IPEC-J2) and the cells were treated with tunicamycin or LPS at specific times. The expression of marker proteins was determined by western blot and immunofluorescence. Possible crosstalk between proteins was analyzed by co-immunoprecipitation. Small interfering RNA transfection was employed to verify the mechanisms. Results: We found that Escherichia coli-derived LPS aggravated ERS and ERS-mediated apoptosis in ERS-responsive IPEC-J2 cells. The crosstalk between nuclear glucose-regulated protein 78 (GRP78) and tumor protein 53 (p53) was verified to trigger this LPS-aggravated apoptosis of ERS-responsive intestinal cells. Conclusion: This novel finding implies that intestinal malfunctions might solely originate from the effects of Gram-negative bacteria on ERS-responsive intestinal cells. The regulation of ERS signaling (especially the crosstalk between nuclear GRP78 and p53) in ERS-responsive/rapidly growing intestines may help intestinal cells survive from Gram-negative bacterial infections.

scholarly journals A pumpless body-on-a-chip model using a primary culture of human intestinal cells and a 3D culture of liver cells

Lab on a Chip ◽  
2018 ◽  
Vol 18 (14) ◽  
pp. 2036-2046 ◽  
Author(s):  
Huanhuan Joyce Chen ◽  
Paula Miller ◽  
Michael L. Shuler
Keyword(s):  
Epithelial Cells ◽  
Primary Culture ◽  
Intestinal Epithelial Cells ◽  
3D Culture ◽  
Intestinal Cells ◽  
Intestinal Epithelial ◽  
Human Intestinal Epithelial Cells ◽  
Improved Model ◽  
Drug Studies ◽  
Human Intestinal Cells

A pumpless GI–Liver system using primary human intestinal epithelial cells serves as an improved model for drug studies.

scholarly journals Expression of Human Decay-Accelerating Factor on Intestinal Epithelium of Transgenic Mice Does Not Facilitate Infection by the Enteral Route

2015 ◽  
Vol 89 (8) ◽  
pp. 4311-4318 ◽  
Author(s):  
Jieyan Pan ◽  
Lili Zhang ◽  
Matthew A. Odenwald ◽  
Le Shen ◽  
Jerrold R. Turner ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Transgenic Mice ◽  
Intestinal Epithelium ◽  
Intestinal Epithelial Cells ◽  
Apical Cell ◽  
Oral Route ◽  
Intestinal Epithelial ◽  
Human Intestinal Epithelial Cells ◽  
Cvb3 Infection

ABSTRACTIn vitro, infection of polarized human intestinal epithelial cells by coxsackievirus B3 (CVB3) depends on virus interaction with decay-accelerating factor (DAF), a receptor expressed on the apical cell surface. Although mice are highly susceptible to CVB3 infection when virus is delivered by intraperitoneal injection, infection by the enteral route is very inefficient. Murine DAF, unlike human DAF, does not bind virus, and we hypothesized that the absence of an accessible receptor on the intestinal surface is an important barrier to infection by the oral route. We generated transgenic mice that express human DAF specifically on intestinal epithelium and measured their susceptibility to infection by a DAF-binding CVB3 isolate. Human DAF permitted CVB3 to bind to the intestinal surfaceex vivoand to infect polarized monolayers of small-intestinal epithelial cells derived from DAF transgenic mice. However, expression of human DAF did not facilitate infection by the enteral route either in immunocompetent animals or in animals deficient in the interferon alpha/beta receptor. These results indicate that the absence of an apical receptor on intestinal epithelium is not the major barrier to infection of mice by the oral route.IMPORTANCECVB3 infection of human intestinal epithelial cells depends on DAF at the apical cell surface, and expression of human DAF on murine intestinal epithelial cells permits their infectionin vitro. However, expression of human DAF on the intestinal surface of transgenic mice did not facilitate infection by the oral route. Although the role of intestinal DAF in human infection has not been directly examined, these results suggest that DAF is not the critical factor in mice.

scholarly journals Campylobacter-Induced Interleukin-8 Secretion in Polarized Human Intestinal Epithelial Cells Requires Campylobacter-Secreted Cytolethal Distending Toxin- and Toll-Like Receptor-Mediated Activation of NF-κB

2008 ◽  
Vol 76 (10) ◽  
pp. 4498-4508 ◽  
Author(s):  
Jie Zheng ◽  
Jianghong Meng ◽  
Shaohua Zhao ◽  
Ruby Singh ◽  
Wenxia Song
Keyword(s):  
Epithelial Cells ◽  
Intestinal Epithelium ◽  
Intestinal Epithelial Cells ◽  
Interleukin 8 ◽  
Cytolethal Distending Toxin ◽  
Intestinal Epithelial ◽  
Toll Like Receptor ◽  
T84 Cells ◽  
Human Intestinal Epithelial Cells ◽  
Tnf Α

ABSTRACT Campylobacter jejuni and Campylobacter coli colonize and infect the intestinal epithelium and cause acute inflammatory diarrhea. The intestinal epithelium serves as a physical barrier to, and a sensor of, bacterial infection by secreting proinflammatory cytokines. This study examined the mechanisms for Campylobacter-induced secretion of the proinflammatory chemokine interleukin-8 (IL-8) by using polarized T84 human colonic epithelial cells as a model. C. jejuni increased the secretion of both IL-8 and tumor necrosis factor alpha (TNF-α) in polarized epithelial cells. However, the increase in IL-8 secretion was independent of Campylobacter-stimulated TNF-α secretion. Polarized T84 cells secreted IL-8 predominantly to the basolateral medium independently of the inoculation direction. While there was a significant correlation between the levels of IL-8 secretion and Campylobacter invasion, all 11 strains tested increased IL-8 secretion by polarized T84 cells despite their differences in adherence, invasion, and transcytosis efficiencies. Cell-free supernatants of Campylobacter-T84-cell culture increased IL-8 secretion to levels similar to those induced by live bacterial inoculation. The ability of the supernatant to induce IL-8 secretion was reduced by flagellum and cytolethal distending toxin (CDT) gene mutants, treatment of the supernatant with protease K or heat, or treatment of T84 cells with the Toll-like receptor (TLR) inhibitor MyD88 inhibitory peptide or chloroquine. NF-κB inhibitors or cdtB mutation plus MyD88 inhibitor, but not flaA cdtB double mutations, abolished the ability of the supernatant to induce IL-8 secretion. Taken together, our results demonstrate that Campylobacter-induced IL-8 secretion requires functional flagella and CDT and depends on the activation of NF-κB through TLR signaling and CDT in human intestinal epithelial cells.

scholarly journals Influence of Exposure Time on Gene Expression by Human Intestinal Epithelial Cells Exposed to Lactobacillus acidophilus

2012 ◽  
Vol 78 (14) ◽  
pp. 5028-5032 ◽  
Author(s):  
Sarah O'Flaherty ◽  
Todd R. Klaenhammer
Keyword(s):  
Gene Expression ◽  
Lactobacillus Acidophilus ◽  
Target Genes ◽  
Intestinal Epithelial Cells ◽  
Intestinal Cells ◽  
Intestinal Epithelial ◽  
Content Type ◽  
Temporal Gene Expression ◽  
Human Intestinal Epithelial Cells ◽  
Human Intestinal Cells

ABSTRACTAnalysis of global temporal gene expression by human intestinal cells when exposed toLactobacillus acidophilusrevealed induction of immune-related pathways and NF-κB target genes after a 1-h exposure, compared to a 4- or 8-h exposure. Additionally, anL. acidophilusderivative expressing covalently bound flagellin resulted in increased induction ofil8,cxc1, andcxcl2compared to the parentL. acidophilus.

scholarly journals Single-cell analyses reveal SARS-CoV-2 interference with intrinsic immune response in the human gut

2020 ◽  
Author(s):  
Sergio Triana ◽  
Camila Metz Zumaran ◽  
Carlos Ramirez ◽  
Carmon Kee ◽  
Patricio Doldan ◽  
...  
Keyword(s):  
Immune Response ◽  
Epithelial Cells ◽  
Intestinal Epithelium ◽  
Intestinal Epithelial Cells ◽  
List Type ◽  
Intestinal Epithelial ◽  
Human Gut ◽  
Interferon Stimulated Genes ◽  
Human Intestinal Epithelial Cells ◽  
Infected Cells

AbstractObjectiveExacerbated pro-inflammatory immune response contributes to COVID-19 pathology. Despite the evidence about SARS-CoV-2 infecting the human gut, little is known about the importance of the enteric phase of SARS-CoV-2 for the viral lifecycle and for the development of COVID-19-associated pathologies. Similarly, it remains unknown whether the innate immune response triggered in this organ to combat viral infection is similar or distinct compared to the one triggered in other organs.DesignWe exploited human ileum- and colon-derived organoids as a non-transformed culture model supporting SARS-CoV-2 infection. We characterized the replication kinetics of SARS-CoV-2 in intestinal epithelial cells and correlated the expression of the viral receptor ACE2 with infection. We performed conventional and targeted single-cell transcriptomics and multiplex single-molecule RNA fluorescence in situ hybridization and used IFN-reporter bioassays to characterize the response of primary human intestinal epithelial cells to SARS-CoV-2 infection.ResultsWe identified a subpopulation of enterocytes as the prime target of SARS-CoV-2. We found the lack of positive correlation between susceptibility to infection and the expression of ACE2 and revealed that SARS-CoV-2 downregulates ACE2 expression upon infection. Infected cells activated strong proinflammatory programs and produced interferon, while expression of interferon-stimulated genes was limited to bystander cells due to SARS-CoV-2 suppressing the autocrine action of interferon in infected cells.ConclusionOur findings reveal that SARS-CoV-2 curtails the immune response in primary human intestinal epithelial cells to promote its replication and spread and this highlights the gut as a proinflammatory reservoir that should be considered to fully understand SARS-CoV-2 pathogenesis.Significance of the studyWhat is already known about this subject?COVID-19 patients have gastrointestinal symptoms which likely correlates with SARS-CoV-2 infection of the intestinal epitheliumSARS-CoV-2 replicates in human intestinal epithelial cells.Intestinal organoids are a good model to study SARS-CoV-2 infection of the gastrointestinal tractThere is a limited interferon response in human lung epithelial cells upon SARS-CoV-2 infection.What are the new findings?A specific subpopulation of enterocytes are the prime targets of SARS-CoV-2 infection of the human gut.There is a lack of correlation between ACE2 expression and susceptibility to SARS-CoV-2 infection. SARS-CoV-2 downregulates ACE2 expression upon infection.Human intestinal epithelium cells produce interferon upon SARS-CoV-2 infection.Interferon acts in a paracrine manner to induce interferon stimulated genes that control viral infection only in bystander cells.SARS-CoV-2 actively blocks interferon signaling in infected cells.How might it impact on clinical practice in the foreseeable future?The absence of correlation between ACE2 levels and susceptibility suggest that medications influencing ACE2 levels (e.g. high blood pressure drugs) will not make patients more susceptible to SARS-CoV-2 infection.The restricted cell tropism and the distinct immune response mounted by the GI tract, suggests that specific cellular restriction/replication factors and organ specific intrinsic innate immune pathways can represent unique therapeutic targets to treat COVD-19 patients by considering which organ is most infected/impacted by SARS-CoV-2.The strong pro-inflammatory signal mounted by the intestinal epithelium can fuel the systemic inflammation observed in COVID-19 patients and is likely participating in the lung specific pathology.

scholarly journals The food additive E171 and titanium dioxide nanoparticles indirectly alter the homeostasis of human intestinal epithelial cells in vitro

2019 ◽  
Vol 6 (5) ◽  
pp. 1549-1561 ◽  
Author(s):  
Marie Dorier ◽  
David Béal ◽  
Céline Tisseyre ◽  
Caroline Marie-Desvergne ◽  
Muriel Dubosson ◽  
...  
Keyword(s):  
Titanium Dioxide ◽  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Titanium Dioxide Nanoparticles ◽  
Food Additive ◽  
Repeated Exposure ◽  
Intestinal Cells ◽  
Intestinal Epithelial ◽  
Human Intestinal Epithelial Cells

Repeated exposure to E171 or TiO2-NPs, in vitro, induce moderate inflammation and mucus secretion in intestinal cells.

scholarly journals Human [Gly2]GLP-2 reduces the severity of colonic injury in a murine model of experimental colitis

1999 ◽  
Vol 276 (1) ◽  
pp. G79-G91 ◽  
Author(s):  
Daniel J. Drucker ◽  
Bernardo Yusta ◽  
Robin P. Boushey ◽  
Lorraine DeForest ◽  
Patricia L. Brubaker
Keyword(s):  
Intestinal Epithelium ◽  
Intestinal Inflammation ◽  
Interleukin 1 ◽  
Experimental Colitis ◽  
Peptide Hormone ◽  
Intestinal Epithelial ◽  
Colonic Injury ◽  
Intestinal Proliferation ◽  
Gastrointestinal Epithelium ◽  
Glucagon Like Peptide

The pathology of Crohn’s disease and ulcerative colitis is characterized by chronic inflammation and destruction of the gastrointestinal epithelium. Although suppression of inflammatory mediators remains the principle component of current disease therapeutics, strategies for enhancing repair and regeneration of the compromised intestinal epithelium have not been widely explored. The demonstration that a peptide hormone secreted by the intestinal epithelium, glucagon-like peptide-2 (GLP-2), is a potent endogenous stimulator of intestinal epithelial proliferation in the small bowel prompted studies of the therapeutic efficacy of GLP-2 in CD1 and BALB/c mice with dextran sulfate (DS)-induced colitis. We report here that a human GLP-2 analog (h[Gly2]GLP-2) significantly reverses weight loss, reduces interleukin-1 expression, and increases colon length, crypt depth, and both mucosal area and integrity in the colon of mice with acute DS colitis. The effects of h[Gly2]GLP-2 in the colon are mediated in part via enhanced stimulation of mucosal epithelial cell proliferation. These observations suggest that exploitation of the normal mechanisms used to regulate intestinal proliferation may be a useful adjunct for healing mucosal epithelium in the presence of active intestinal inflammation.

scholarly journals Rotavirus Infection Induces Cytoskeleton Disorganization in Human Intestinal Epithelial Cells: Implication of an Increase in Intracellular Calcium Concentration

2000 ◽  
Vol 74 (22) ◽  
pp. 10801-10806 ◽  
Author(s):  
Jean-Philippe Brunet ◽  
Nathalie Jourdan ◽  
Jacqueline Cotte-Laffitte ◽  
Catherine Linxe ◽  
Monique Géniteau-Legendre ◽  
...  
Keyword(s):  
Calcium Concentration ◽  
Intestinal Cells ◽  
Intestinal Epithelial ◽  
Cytokeratin 18 ◽  
Structural Alterations ◽  
Rotavirus Infection ◽  
Differentiated Cells ◽  
Human Intestinal Epithelial Cells

ABSTRACT Rotavirus infection is the most common cause of severe infantile gastroenteritis worldwide. In vivo, rotavirus exhibits a marked tropism for the differentiated enterocytes of the intestinal epithelium. In vitro, differentiated and undifferentiated intestinal cells can be infected. We observed that rotavirus infection of the human intestinal epithelial Caco-2 cells induces cytoskeleton alterations as a function of cell differentiation. The vimentin network disorganization detected in undifferentiated Caco-2 cells was not found in fully differentiated cells. In contrast, differentiated Caco-2 cells presented Ca2+-dependent microtubule disassembly and Ca2+-independent cytokeratin 18 rearrangement, which both require viral replication. We propose that these structural alterations could represent the first manifestations of rotavirus-infected enterocyte injury leading to functional perturbations and then to diarrhea.

scholarly journals Interferon Regulatory Factor 1 (IRF-1) and IRF-2 Distinctively Up-Regulate Gene Expression and Production of Interleukin-7 in Human Intestinal Epithelial Cells

2004 ◽  
Vol 24 (14) ◽  
pp. 6298-6310 ◽  
Author(s):  
Shigeru Oshima ◽  
Tetsuya Nakamura ◽  
Shin Namiki ◽  
Eriko Okada ◽  
Kiichiro Tsuchiya ◽  
...  
Keyword(s):  
Gene Expression ◽  
Epithelial Cells ◽  
Intestinal Mucosa ◽  
Intestinal Epithelial Cells ◽  
Core Promoter ◽  
Expression Patterns ◽  
Intestinal Epithelial ◽  
Regulatory Factor ◽  
Human Intestinal Epithelial Cells ◽  
Ifn Γ

ABSTRACT Intestinal epithelial cell-derived interleukin (IL)-7 functions as a pleiotropic and nonredundant cytokine in the human intestinal mucosa; however, the molecular basis of its production has remained totally unknown. We here showed that human intestinal epithelial cells both constitutively and when induced by gamma interferon (IFN-γ) produced IL-7, while several other factors we tested had no effect. Transcriptional regulation via an IFN regulatory factor element (IRF-E) on the 5′ flanking region, which lacks canonical core promoter sequences, was pivotal for both modes of IL-7 expression. IRF-1 and IRF-2, the latter of which is generally known as a transcriptional repressor, were shown to interact with IRF-E and transactivate IL-7 gene expression in an IFN-γ-inducible and constitutive manner, respectively. Indeed, tetracycline-inducible expression experiments revealed that both of these IRF proteins up-regulated IL-7 protein production, and their exclusive roles were further confirmed by small interfering RNA-mediated gene silencing systems. Moreover, these IRFs displayed distinct properties concerning the profile of IL-7 transcripts upon activation and expression patterns within human colonic epithelial tissues. These results suggest that the functional interplay between IRF-1 and IRF-2 serves as an elaborate and cooperative mechanism for timely as well as continuous regulation of IL-7 production that is essential for local immune regulation within human intestinal mucosa.

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