• Journal of Life Science
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• v.26 no.5
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• pp.531-536
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• 2016

We previously showed that NAD(P)H:quinone oxidoreductase 1 (NQO1) knockout (KO) mice exhibited spontaneous inflammation with markedly increased mucosal permeability in the gut, and that NQO1 is functionally associated with regulating tight junctions in the mucosal epithelial cells that govern the mucosal barrier. Here, we confirm the role of NQO1 in the formation of tight junctions by human colonic epithelial cells (HT29). We treated HT29 cells with a chemical inhibitor of NQO1 (dicumarol; 10 μM), and examined the effect on the transepithelial resistance of epithelial cells and the protein expression levels of ZO1 and occludin (two known regulators of tight junctions between gut epithelial cells). The dicumarol-induced inhibition of NQO1 markedly reduced transepithelial resistance (a measure of tight junctions) and decreased the levels of the tested tight junction proteins. In vivo, luminal injection of dicumarol significantly increased mucosal permeability and decreased ZO1 and occludin protein expression levels in mouse guts. However, in contrast to the previous report that the epithelial cells of NQO1 KO mice showed marked down-regulations of the transcripts encoding ZO1 and occludin, these transcript levels were not affected in dicumarol-treated HT29 cells. This result suggests that the NQO1-depedent regulation of tight junction molecules may involve multiple processes, including both transcriptional regulation and protein degradation processes such as those governed by the ubiquitination/proteasomal, and/or lysosomal systems.

• Biomolecules & Therapeutics
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• v.29 no.2
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• pp.175-183
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• 2021

The mitogen-activated protein kinase (MAPK) pathway controls intestinal epithelial barrier permeability by regulating tight junctions (TJs) and epithelial cells damage. Heme oxygenase-1 (HO-1) and carbon monoxide (CO) protect the intestinal epithelial barrier function, but the molecular mechanism is not yet clarified. MAPK activation and barrier permeability were studied using monolayers of Caco-2 cells treated with tissue necrosis factor α (TNF-α) transfected with FUGW-HO-1 or pLKO.1-sh-HO-1 plasmid. Intestinal mucosal barrier permeability and MAPK activation were also investigated using carbon tetrachloride (CCl4) administration with CoPP (a HO-1 inducer), ZnPP (a HO-1 inhibitor), CO releasing molecule 2 (CORM-2), or inactived-CORM-2-treated wild-type mice and mice with HO-1 deficiency in intestinal epithelial cells. TNF-α increased epithelial TJ disruption and cleaved caspase-3 expression, induced ERK, p38, and JNK phosphorylation. In addition, HO-1 blocked TNF-α-induced increase in epithelial TJs disruption, cleaved caspase-3 expression, as well as ERK, p38, and JNK phosphorylation in an HO-1-dependent manner. CoPP and CORM-2 directly ameliorated intestinal mucosal injury, attenuated TJ disruption and cleaved caspase-3 expression, and inhibited epithelial ERK, p38, and JNK phosphorylation after chronic CCl4 injection. Conversely, ZnPP completely reversed these effects. Furthermore, mice with intestinal epithelial HO-1 deficient exhibited a robust increase in mucosal TJs disruption, cleaved caspase-3 expression, and MAPKs activation as compared to the control group mice. These data demonstrated that HO-1-dependent MAPK signaling inhibition preserves the intestinal mucosal barrier integrity by abrogating TJ dysregulation and epithelial cell damage. The differential targeting of gut HO-1-MAPK axis leads to improved intestinal disease therapy.

• BMB Reports
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• v.49 no.5
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• pp.263-269
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• 2016

The intestine represents the largest and most elaborate immune system organ, in which dynamic and reciprocal interplay among numerous immune and epithelial cells, commensal microbiota, and external antigens contributes to establishing both homeostatic and pathologic conditions. The mechanisms that sustain gut homeostasis are pivotal in maintaining gut health in the harsh environment of the gut lumen. Intestinal epithelial cells are critical players in creating the mucosal platform for interplay between host immune cells and luminal stress inducers. Thus, knowledge of the epithelial interface between immune cells and the luminal environment is a prerequisite for a better understanding of gut homeostasis and pathophysiologies such as inflammation. In this review, we explore the importance of the epithelium in limiting or promoting gut inflammation (e.g., inflammatory bowel disease). We also introduce recent findings on how small RNAs such as microRNAs orchestrate pathophysiologic gene regulation.

• The Journal of Korean Academy of Prosthodontics
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• v.29 no.2
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• pp.211-223
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• 1991

This study was aimed to observe the histological changes of the edentulous and denture wearing alveolar ridge mucosa. The distribution of Langerhans cells was also observed to investigate the mucosal immune response by denture wearing. The mucosal tissues were obtained from of 12 cases of edentulous nondenture wearers(NDW), 7 cases of denture wearers(DW), and 12 cases of flabby tissues(FT). For the identification of Langerhans cells of the mucosal epithelia, the immunohistochemical stain for S-100 protein was applied. The results were as follows : 1. 7 cases among 12 cases of NDW showed hyperkeratosis, and 5 cases were covered by parakeratosis, whereas 3 cases among 7 cases of DW showed hyperkeratosis, and 4 cases showed parakeratosis on the mucosal epithelium. All cases of both DW and NDW demonstrated epithelial hyperplasia, except. 2 cases of DW, which showed epithelial atrophy. The content of glycogen in the epithelial layer showed the decrease in the group of DW. 2. Both NDW and DW showed the infiltration of chronic inflammatory cells. The collagen fibers tended to be arranged densely and irregularly in cases of denture wearing period more than 10 years. 3. FT showed variable epithelial changes from epithelial atrophy to marked hyperplasia, and the pattern of keratinization was also variable. The collagen fibers tended to be arranged irregularly. 4. The distribution of Langerhans cells showed the increase of 1.84-1.96 times in the group of DW compared with NDW group.

• Journal of Microbiology and Biotechnology
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• v.27 no.4
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• pp.694-700
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• 2017

Clostridium difficile, which causes pseudomembranous colitis, releases toxin A and toxin B. These toxins are considered to be the main causative agents for the disease pathogenesis, and their expression is associated with a marked increase of apoptosis in mucosal epithelial cells. Colonic epithelial cells are believed to form a physical barrier between the lumen and the submucosa, and abnormally increased mucosal epithelial cell apoptosis is considered to be an initial step in gut inflammation responses. Therefore, one approach to treating pseudomembranous colitis would be to develop agents that block the mucosal epithelial cell apoptosis caused by toxin A, thus restoring barrier function and curing inflammatory responses in the gut. We recently isolated an antimicrobial peptide, Periplanetasin-2 (Peri-2, YPCKLNLKLGKVPFH) from the American cockroach, whose extracts have shown great potential for clinical use. Here, we assessed whether Peri-2 could inhibit the cell toxicity and inflammation caused by C. difficile toxin A. Indeed, in human colonocyte HT29 cells, Peri-2 inhibited the toxin A-induced decrease in cell proliferation and ameliorated the cell apoptosis induced by this toxin. Moreover, in the toxin A-induced mouse enteritis model, Peri-2 blocked the mucosal disruption and inflammatory response caused by toxin A. These results suggest that the American cockroach peptide Peri-2 could be a possible drug candidate for addressing the pseudomembranous colitis caused by C. difficile toxin A.

• Journal of Oral Medicine and Pain
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• v.24 no.3
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• pp.261-267
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• 1999

The present investigation was carried out to identify salivary components of mucosal pellicle and to explore the difference of mucosal pellicle components according to the location of oral mucosa. By using antisera and immunoblotting, high-(MG1) and low-(MG2) molecular-mass salivary mucins, amylase, IgA, proline-rich proteins(PRPs) were detected in mucosal pellicle in vivo. In addition, the data indicated that mucins, IgA and proline-rich proteins could be cleaved into lower-molecular-mass products, whereas the IgA, proline-rich proteins could also be cross-linked into higher-molecular-mass complexes. Mucosal pellicles from buccal, labial and palatal mucosa showed similar pattern in immunoblotting experiments using anti-MG2 and anti-PRPs antisera. The data from this study suggest that during mucosal pellicle formation multiple components of saliva adsorb to oral mucosal epithelial cell surfaces, and selected components can be proteolytically cleaved into smaller fragments and/or cross-linked into higher-molecular products.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.132.2-132.2
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• 2003

Vibrio vulnificus, a Gram-negative estuarine bacterium, is the causative agent of food-borne diseases, such as life-threatening septicemia. V. vulnificus penetrating into the intestinal epithelial barrier stimulates an inflammatory response in the adjacent intestinal mucosa. Therefore, interaction between V. vulnificus and intestinal cells is important for understanding of both the immunology of mucosal surfaces and V. vulnificus. In this study we investigated the effects of V. vulnificus infection on cytokine gene expression of human intestinal epithelial cells, Caco-2 and INT-407 cells. (omitted)

• Journal of Sasang Constitutional Medicine
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• v.14 no.1
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• pp.100-111
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• 2002

1. The Purpose of study An experimental study has done to examine the effect of defense on gastric mucosal damage of Jowesungcheong-tang. 2. The Material and Method of study Mice had intragastric injected with JST extract before indome thacin treatment which induces hemorrh age erosion artificially. General morphology, infiltrative cell in mucosa, the distribution of UEA-I, COX-1, MAC-1. ICAM, and Apoptotic cell were objected (Ahhreviation) JST :Jowesungcheong-tang, UEA-I : ulex europaeus agglutinin-I, COX-1: cyclooxyhenase-1, ICAM : intercellular adhesion molecule-1, GPE : Gastropathy elicitated mice 3. The results and Conclusions of study 1) The degree of hemorrhage erosion in GPE-group had increased conspicuously in gastric gland proper. JST -group were the same as normal 2) The noticeable increase of granular lecocytes and lymphocytes in GEP-group were seen, but in JST group, the configuration is decreased 3) The decrease of UEA-I positive reacted cells, COX-1, surface epithelial cells and the increase of MAC-l positive cells, ICAM-l positive cells had shown in GPE-group, but in JST-group UEA-I positive cells, COX-1 surface epithelial cells were in creased and MAC-1 positive cells, ICAM-l positive cells were decreased than GPE-group. 4) A number of apoptotic cells were distributed in hemorrhage erosion. The remarkable decrease of apoptotic cells were shown in JST-group.

• Journal of Microbiology and Biotechnology
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• v.31 no.8
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• pp.1175-1182
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• 2021

We investigated the effect of bovine lactoferricin (Lfcin-B), a peptide derived from bovine lactoferrin, on activation of intestinal epithelial cells in IEC-6 intestinal cell, and protection against in vivo rotavirus (RV) infection. Treatment with Lfcin-B significantly enhanced the growth of IEC-6 cells and increased their capacity for attachment and spreading in culture plates. Also, Lfcin-B synergistically augmented the binding of IEC-6 cells to laminin, a component of the extracellular matrix (ECM). In the analysis of the intracellular mechanism related to Lfcin-B-induced activation of IEC-6 cells, this peptide upregulated tyrosine-dependent phosphorylation of focal adhesion kinase (FAK) and paxillin, which are intracellular proteins associated with cell adhesion, spreading, and signal transduction during cell activation. An experiment using synthetic peptides with various sequences of amino acids revealed that a sequence of 9 amino acids (FKCRRWQWR) corresponding to 17-25 of the N-terminus of Lfcin-B is responsible for the epithelial cell activation. In an in vivo experiment, treatment with Lfcin-B one day before RV infection effectively prevented RV-induced diarrhea and significantly reduced RV titers in the bowels of infected mice. These results suggest that Lfcin-B plays meaningful roles in the maintenance and repair of intestinal mucosal tissues, as well as in protecting against intestinal infection by RV. Collectively, Lfcin-B is a promising candidate with potential applications in drugs or functional foods beneficial for intestinal health and mucosal immunity.

• Korean Journal of Veterinary Research
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• v.56 no.2
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• pp.57-66
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• 2016

The gut epithelial barrier, which is composed of the mucosal layer and the intestinal epithelium, has multiple defense mechanisms and interconnected regulatory mechanisms against enteric microbial pathogens. However, many bacterial pathogens have highly evolved infectious stratagems that manipulate mucin production, epithelial cell-cell junctions, cell death, and cell turnover to promote their replication and pathogenicity in the gut epithelial barrier. In this review, we focus on current knowledge about how bacterial pathogens regulate mucin levels to circumvent the epithelial mucus barrier and target cell-cell junctions to invade deeper tissues and increase their colonization. We also describe how bacterial pathogens manipulate various modes of epithelial cell death to facilitate bacterial dissemination and virulence effects. Finally, we discuss recent investigating how bacterial pathogens regulate epithelial cell turnover and intestinal stem cell populations to modulate intestinal epithelium homeostasis.