Pathogenic Bacteria Induce Colonic PepT1 Expression: An Implication in Host Defense Response

Nguyen, Hang Thi Thu; Dalmasso, Guillaume; Powell, Kimberly R.; Yan, Yutao; Bhatt, Shantanu; Kalman, Daniel; Sitaraman, Shanthi V.; Merlin, Didier

doi:10.1053/j.gastro.2009.06.043

Cited by 29 publications

(28 citation statements)

References 39 publications

(60 reference statements)

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“…Pathogenic bacteria (Nguyen et al, 2009) and lipopolysaccharides (Shu et al, 2002), the major components of the outer layer of Gram-negative bacteria, can also affect the expression of SLC15A1, which can transport bacterial peptides. Our trial was not designed to assess the impact of thymol on gastrointestinal microbiota because its antibacterial properties are well known, and thus we cannot speculate here on possible variations on the gastric bacteria profile.…”

Section: Discussionmentioning

confidence: 99%

“…Our trial was not designed to assess the impact of thymol on gastrointestinal microbiota because its antibacterial properties are well known, and thus we cannot speculate here on possible variations on the gastric bacteria profile. Nevertheless, it is worth mentioning that transgenic mice overexpressing SLC15A1 and infected with Citrobacter rodentium had reduced colonic colonization by this microbe, compared with that observed in infected wild-type mice Effect of thymol on gene expression in pig stomach (Nguyen et al, 2009). Intriguingly, in a previous in vivo trial, we found that Citrobacter freundii, a microbe closely related to C. rodentium, was increased in the intestinal content of pigs fed thymol compared with that observed in control pigs (Jankzyk et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

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Effect of free thymol on differential gene expression in gastric mucosa of the young pig

Colombo

Priori

Gandolfi

et al. 2014

Animal

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Thymol is the most common molecule in thyme and has been proposed as an oral alternative to antibiotics in the feed of pigs and broilers. The knowledge of the in vivo physiological effects of thymol on tissues is limited, particularly its impact on the gastric mucosa, where it is primarily absorbed when it is orally supplied. In this study, thymol (TH, 50 mg/ kg BW) or a placebo (CO) was introduced directly into the stomach of 8 weaned pigs that were slaughtered 12 h later and sampled for gastric oxyntic and pyloric mucosa. The analysis of whole transcript expression was performed using Affymetrix © Porcine Gene 1.1 ST array strips. Affymetrix Transcripts IDs were associated with 13 406 human gene names based on Sus scrofa Ensemble. Gene Set Enrichment Analysis was performed, comparing TH and CO pigs. For each gene set, the normalized enrichment score (NES) was defined as significant when the false discovery rate % was <25 and the P-value of NES was <0.05. In response to TH, 72 and 19 gene sets were significantly enriched in the oxyntic and pyloric mucosa, respectively. Several gene sets involved in mitosis and its regulation ranked near the top, primarily in the oxyntic mucosa; the gene set DIGESTION ranked first and ninth in the pyloric and oxyntic mucosa, respectively. Within this group, somatostatin (SST), SST receptors, peptide transporter 1 (SLC15A1) and calpain 9 (gastrointestinal tract-specific calpain) were the most strongly upregulated genes. Thymol reduced the enrichment of 120 and 59 gene sets in the oxyntic and pyloric mucosa, respectively. Several gene sets related to ion transport and channeling and aqueous pores across membranes, including short transient receptor potential (TRP) channel 4, potassium voltage-gated channel members 1 and 2, and ryanodine receptors 2 and 3, were less enriched. The downregulation of these genes sensitive to thymol in vitro could depend on the thymol dose and contact with the gastric tissues that causes an adaptive response with their reduced activation. Conversely, the activation of the TRPA1 gene (ranked 1072 and 128 among all the genes in the oxyntic and pyloric mucosa, respectively) indicates the involvement of another TRP-regulating cellular calcium storage. In conclusion, the stimulation of gastric proliferative activity and the control of digestive activity by thymol can influence positively gastric maturation and function in the weaned pigs. These properties should be considered in addition to thymol's antimicrobial properties when supplementation of this molecule in feed is evaluated.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Effect of free thymol on differential gene expression in gastric mucosa of the young pig

Colombo

Priori

Gandolfi

et al. 2014

Animal

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“…The apical activity of SERT is decreased following tEPEC infection of fully differentiated Caco-2 cells in a T3SS-dependent manner, but its expression at the brush border is unaffected (622). Intimate attachment of tEPEC to fully differentiated HT29-Cl.19A cells is followed by increased hPet1 expression and activity by activation of the transcription factor Cdx2 (623). Deletion of the escN, espA, espB, and espD genes, which encode parts of T3SS, and the gene encoding BFP revealed that both early and intimate tEPEC attachment are needed for the EPEC inhibitory effect on the apical sodium-dependent bile acid transporter to occur in fully differentiated Caco-2 cells (624).…”

Section: Structural and Functional Injuriesmentioning

confidence: 96%

Pathogenesis of Human Enterovirulent Bacteria: Lessons from Cultured, Fully Differentiated Human Colon Cancer Cell Lines

Moal

Servin

2013

Microbiol Mol Biol Rev

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SUMMARY Hosts are protected from attack by potentially harmful enteric microorganisms, viruses, and parasites by the polarized fully differentiated epithelial cells that make up the epithelium, providing a physical and functional barrier. Enterovirulent bacteria interact with the epithelial polarized cells lining the intestinal barrier, and some invade the cells. A better understanding of the cross talk between enterovirulent bacteria and the polarized intestinal cells has resulted in the identification of essential enterovirulent bacterial structures and virulence gene products playing pivotal roles in pathogenesis. Cultured animal cell lines and cultured human nonintestinal, undifferentiated epithelial cells have been extensively used for understanding the mechanisms by which some human enterovirulent bacteria induce intestinal disorders. Human colon carcinoma cell lines which are able to express in culture the functional and structural characteristics of mature enterocytes and goblet cells have been established, mimicking structurally and functionally an intestinal epithelial barrier. Moreover, Caco-2-derived M-like cells have been established, mimicking the bacterial capture property of M cells of Peyer's patches. This review intends to analyze the cellular and molecular mechanisms of pathogenesis of human enterovirulent bacteria observed in infected cultured human colon carcinoma enterocyte-like HT-29 subpopulations, enterocyte-like Caco-2 and clone cells, the colonic T84 cell line, HT-29 mucus-secreting cell subpopulations, and Caco-2-derived M-like cells, including cell association, cell entry, intracellular lifestyle, structural lesions at the brush border, functional lesions in enterocytes and goblet cells, functional and structural lesions at the junctional domain, and host cellular defense responses.

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“…For infecting WT and CD98 Tg mice with C. rodentium, food and drinking water were replaced with 20% sucrose containing C. rodentium (3.3 ϫ 10 7 CFU/ml) in distilled water overnight as previously described (36). Control groups were given normal drinking water.…”

Section: Methodsmentioning

confidence: 99%

“…Colonic tissues were cultured in RPMI 1640 medium (Cellgro, Manassas, VA) with FBS as described previously (36). Briefly, 5-to 10-mm colon tissues of WT and CD98 Tg mice were placed on sterile foam squares in 6-well culture plates with the mucosal surface facing upwards.…”

Section: Methodsmentioning

confidence: 99%

Intestinal Epithelial CD98 Directly Modulates the Innate Host Response to Enteric Bacterial Pathogens

et al. 2013

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e CD98 is a type II transmembrane glycoprotein whose expression increases in intestinal epithelial cells (IECs) during intestinal inflammation. Enteropathogenic Escherichia coli (EPEC) is a food-borne human pathogen that attaches to IECs and injects effector proteins directly into the host cells, thus provoking an inflammatory response. In the present study, we investigated CD98 and EPEC interactions in vitro and ex vivo and examined FVB wild-type (WT) and villin-CD98 transgenic mice overexpressing human CD98 in IECs (hCD98 Tg mice) and infected with Citrobacter rodentium as an in vivo model. In vivo studies indicated that CD98 overexpression, localized to the apical domain of colonic cells, increased the attachment of C. rodentium in mouse colons and resulted in increased expression of proinflammatory markers and decreased expression of anti-inflammatory markers. The proliferative markers Ki-67 and cyclin D1 were significantly increased in the colonic tissue of C. rodentium-infected hCD98 Tg mice compared to that of WT mice. Ex vivo studies correlate with the in vivo data. Small interfering RNA (siRNA) studies with Caco2-BBE cells showed a decrease in adherence of EPEC to Caco2 cells in which CD98 expression was knocked down. In vitro surface plasmon resonance (SPR) experiments showed direct binding between recombinant hCD98 and EPEC/C. rodentium proteins. We also demonstrated that the partial extracellular loop of hCD98 was sufficient for direct binding to EPEC/C. rodentium. These findings demonstrate the importance of the extracellular loop of CD98 in the innate host defense response to intestinal infection by attaching and effacing (A/E) pathogens.

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Pathogenic Bacteria Induce Colonic PepT1 Expression: An Implication in Host Defense Response

Cited by 29 publications

References 39 publications

Effect of free thymol on differential gene expression in gastric mucosa of the young pig

Effect of free thymol on differential gene expression in gastric mucosa of the young pig

Pathogenesis of Human Enterovirulent Bacteria: Lessons from Cultured, Fully Differentiated Human Colon Cancer Cell Lines

Intestinal Epithelial CD98 Directly Modulates the Innate Host Response to Enteric Bacterial Pathogens

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