• Title/Summary/Keyword: Tight junction

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Effects of Natural Mineral Water on Reflux Esophagitis (역류성 식도염에 대한 천연 미네랄 워터의 효과)

  • Choo, Byung-Kil
    • Korean Journal of Organic Agriculture
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    • v.30 no.1
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    • pp.75-87
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    • 2022
  • Reflux esophagitis (RE) is a gastroesophageal reflux disease (GERD) caused by repeated reflux of gastric acid into the esophagus. The present study investigated the protective effect of natural mineral water on esophageal injury induced by gastric acid reflux. The cytotoxicity of mineral water was confirmed using Cell viability, proliferation and cytotoxicity assay kit. The protective effect of mineral water on esophageal injury was investigated in RE rat model. The results showed that no cytotoxicity of mineral water was observed in RAW264.7 cells. Mineral water decreased the ratio of esophageal damage, inhibited the increase of inflammatory-protein expression levels and increased the mucosa protection and tight junction proteins expression level in RE control rat. The results suggest that mineral water may have the potential to protect esophageal damage caused by gastric acid reflux and the potential to alleviate reflux esophagitis.

Cheonggukjang Fermented with Bacillus subtilis SCGB574 Ameliorates High Fat Diet-Deteriorated Large Intestinal Health in Rat Model

  • Jae Ho, Choi;Jiyon, Kim;Taekyun, Shin;Myeong Seon, Ryu;Hee-Jong, Yang;Do-Youn, Jeong;Hong-Seok, Son;Tatsuya, Unno
    • Microbiology and Biotechnology Letters
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    • v.50 no.4
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    • pp.522-532
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    • 2022
  • Cheonggukjang is a traditional fermented food in Korea, which is known to exert beneficial effects on health. In this study, we evaluated the effects of cheonggukjang fermented by Bacillus subtilis SCGB 574 (B574) on high fat diet (HFD)-deteriorated large intestinal health. Rats were fed with HFD or HFD supplemented with 10.1% cheonggukjang (B574). Fecal microbiota was analyzed based on 16S rRNA gene sequences, and the fecal and serum metabolome were measured using GC-MS. Our results showed that SCGB574 intake significantly reduced body weight, restored tight junction components, and ameliorated inflammatory cell infiltration. SCGB574 also shifted gut microbiota by increasing the abundance of short chain fatty acid producers such as Alistipes and Flintibacter, although it decreased the abundance of Lactobacillus. Serum and fecal metabolome analyses showed significantly different metabolic profiles between the groups. The top five metabolites increased by SCGB574 were i) arginine biosynthesis, ii) alanine, aspartate, and glutamate metabolism; iii) starch and sucrose metabolism; iv) neomycin, kanamycin, and gentamicin biosynthesis; and v) galactose metabolism. These results showed that cheonggukjang fermented by SCGB574 ameliorates adverse effects of HFD through improving intestinal health.

Change in intestinal alkaline phosphatase activity is a hallmark of antibiotic-induced intestinal dysbiosis

  • Wijesooriya Mudhiyanselage Nadeema Dissanayake;Malavige Romesha Chandanee;Sang-Myeong Lee;Jung Min Heo;Young-Joo Yi
    • Animal Bioscience
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    • v.36 no.9
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    • pp.1403-1413
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    • 2023
  • Objective: Intestinal alkaline phosphatase (IAP) maintains intestinal homeostasis by detoxifying bacterial endotoxins and regulating gut microbiota, and lipid absorption. Antibiotics administered to animals can cause gut dysbiosis and barrier disruption affecting animal health. Therefore, the present study sought to investigate the role of IAP in the intestinal environment in dysbiosis. Methods: Young male mice aged 9 weeks were administered a high dose of antibiotics to induce dysbiosis. They were then sacrificed after 4 weeks to collect the serum and intestinal organs. The IAP activity in the ileum and the level of cytokines in the serum samples were measured. Quantitative real-time polymerase chain reaction analysis of RNA from the intestinal samples was performed using primers for tight junction proteins (TJPs) and proinflammatory cytokines. The relative intensity of IAP and toll-like receptor 4 (TLR4) in intestinal samples was evaluated by western blotting. Results: The IAP activity was significantly lower in the ileum samples of the dysbiosis-induced group compared to the control. The interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha concentrations were significantly higher in the ileum samples of the dysbiosis-induced group. The RNA expression levels of TJP2, claudin-3, and claudin-11 showed significantly lower values in the intestinal samples from the dysbiosis-induced mice. Results from western blotting revealed that the intensity of IAP expression was significantly lower in the ileum samples of the dysbiosis-induced group, while the intensity of TLR4 expression was significantly higher compared to that of the control group without dysbiosis. Conclusion: The IAP activity and relative mRNA expression of the TJPs decreased, while the levels of proinflammatory cytokines increased, which can affect intestinal integrity and the function of the intestinal epithelial cells. This suggests that IAP is involved in mediating the intestinal environment in dysbiosis induced by antibiotics and is an enzyme that can potentially be used to maintain the intestinal environment in animal health care.

Lactic Acid Bacteria Isolated from Human Breast Milk Improve Colitis Induced by 2,4,6-Trinitrobenzene Sulfonic Acid by Inhibiting NF-κB Signaling in Mice

  • Kyung-Joo Kim;Suhyun Kyung;Hui Jin;Minju Im;Jae-won Kim;Hyun Su Kim;Se-Eun Jang
    • Journal of Microbiology and Biotechnology
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    • v.33 no.8
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    • pp.1057-1065
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    • 2023
  • Inflammatory bowel disease (IBD), a chronic inflammatory disease, results from dysregulation of the immune responses. Some lactic acid bacteria (LAB), including Lactobacillus, alleviate IBD through immunomodulation. In this study, the anti-colitis effect of LAB isolated from human breast milk was investigated in a mouse model induced acute colitis with 2,4,6-trinitrobenzene sulfonic acid (TNBS). TNBS remarkably increased weight loss, colon shortening, and colonic mucosal proliferation, as well as the expression levels of inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-1β. Oral administration of LAB isolated from human breast milk resulted in a reduction in TNBS-induced colon shortening, as well as induced cyclooxygenase (COX)-2, nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-κB). In addition, LAB suppressed inflammatory cytokines such as TNF-α, IL-6, and IL-1β, and thus showed an effect of suppressing the level of inflammation induced by TNBS. Furthermore, LAB alleviated gut microbiota dysbiosis, and inhibited intestinal permeability by increasing the expression of intestinal tight junction protein including ZO-1. Collectively, these results suggest that LAB isolated from human breast milk can be used as a functional food for colitis treatment by regulating NF-κB signaling, gut microbiota and increasing expression of intestinal tight junction protein.

PDZ Domain-containing Proteins at Autotypic Junctions in Myelinating Schwann Cells (수초화 슈반세포 autotypic 세포연접의 PDZ 도메인 보유 단백질)

  • Han, Seongjohn;Park, Hyeongbin;Hong, Soomin;Lee, Donghyun;Choi, Maro;Cho, Jeongmok;Urm, Sang-Hwa;Jang, Won Hee;Seog, Dae-Hyun
    • Journal of Life Science
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    • v.25 no.1
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    • pp.101-112
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    • 2015
  • A type of cell junction that is formed between different parts within the same cell is called autotypic cell junction. Autotypic junction proteins form tight junctions found between membrane lamellae of a cell, especially in myelinating glial cells. Some of them have postsynaptic density-95/disks large/zonula occludens-1 (PDZ) domains, which interact with the carboxyl (C)-terminal PDZ-binding motif of other proteins. PDZ domains are protein-protein interaction modules that play a role in protein complex assembly. The PDZ domain, which is widespread in bacteria, plants, yeast, metazoans, and Drosophila, allows the assembly of large multi-protein complexes. The multi-protein complexes act in intracellular signal transduction, protein targeting, and membrane polarization. The identified PDZ domain-containing proteins located at autotypic junctions include zonula occludens-1 (ZO-1), ZO-2, pals-1-associated tight junction protein (PATJ), multi-PDZ domain proteins (MUPPs), membrane-associated guanylate kinase inverted 2 (MAGI2), and protease-activated receptor (PAR)-3. PAR-3 interacts with atypical protein kinase C and PAR-6, forming a ternary complex, which plays an important role in the regulation of cell polarity. MAGI2 interacts with ${\alpha}$-amino-3-hydroxyl-5-methyl-4-isoxazole propionate (AMPA) receptor at excitatory synapses. PATJ is detected in paranodal loops associated with claudin-1. On the other hand, MUPP1 is found in mesaxons and Schmidt-Lanterman incisures with claudin-5. ZO-1, ZO-2, and PAR-3 are found at all three sites. Different distributions of PDZ domain-containing proteins affect the development of autotypic junctions. In this review, we will describe PDZ domain-containing proteins at autotypic tight junctions in myelinating Schwann cells and their roles.

Assessment of Reproductive Health Risk of Polychlorinated Biphenyls by Monitoring the Expression of Claudius and Transepithelial Electrical Resistance in Mouse Sertoli Cells

  • Gye, Myung-Chan;Seiichiroh Ohsako;Lee, Ho-Joon
    • Journal of Microbiology and Biotechnology
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    • v.13 no.4
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    • pp.495-500
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    • 2003
  • Tight junctions (TJ) between adjacent Sertoli cells in testis are important for the formation of the blood testis barrier (BTB). In an effort to verify the reproductive health risk of endocrine-active chemicals (EACs), changes in the transepithelial electrical resistance (TER) and the expression of TJ genes were examined by co-planar polychlorinated biphenyl (PCB) treatment in cultured mouse Sertoli cells. Although the increase in TER of Sertoli cells was accelerated by 10 nM co-planar PCB, it was downregulated by 100 nM co-planar PCB. The expression of claudin-1 was downregulated by co-planar PCB in a concentration-dependent manner. On the contrary, the expression of claudin-1 was increased in the Sertoli cells by 10 nM co-planar PCB treatment. These results suggest that the structure and function of TJ may be targeted by co-planar PCB in Sertoli cells. Assessment of the structure and function of TJ in Sertoli cells might be useful for screening the reproductive health risk of EACs.

Metabolites of Latilactobacillus curvatus BYB3 and Indole Activate Aryl Hydrocarbon Receptor to Attenuate Lipopolysaccharide-Induced Intestinal Barrier Dysfunction

  • Wang, Xing;Yong, Cheng Chung;Oh, Sejong
    • Food Science of Animal Resources
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    • v.42 no.6
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    • pp.1046-1060
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    • 2022
  • This study aimed to investigate the effects of the metabolites of Latilactobacillus curvatus BYB3 and indole-activated aryl hydrocarbon receptor (AhR) to increase the tight junction (TJ) proteins in an in vitro model of intestinal inflammation. In a Western blot assay, the metabolites of L. curvatus BYB3 reduced the TJ demage in lipoploysaccharide (LPS) stimulated-Caco-2 cells. This reduction was a result of upregulating the expression of TJ-associated proteins and suppressing the nuclear factor-κB signaling. Immunofluorescence images consistently revealed that LPS disrupted and reduced the expression of TJ proteins, while the metabolites of L. curvatus BYB3 and indole reversed these alterations. The protective effects of L. curvatus BYB3 were observed on the intestinal barrier function when measuring transepithelial electrical resistance. Using high-performance liquid chromatography analysis the metabolites, the indole-3-latic acid and indole-3-acetamide concentrations were found to be 1.73±0.27 mg/L and 0.51±0.39 mg/L, respectively. These findings indicate that the metabolites of L. curvatus BYB3 have increasing mRNA expressions of cytochrome P450 1A1 (CYP1A1) and AhR, and may thus be applicable for therapy of various inflammatory gut diseases as postbiotics.

Effect of Sabaek-san Extract on Skin Damage Recovery in Atopic Dermatitis-induced Mice (사백산추출물의 아토피피부염 유발 백서에서의 피부장벽 손상 회복 효과)

  • Ahn Sang Hyun;Kim Ki Bong
    • The Journal of Pediatrics of Korean Medicine
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    • v.37 no.4
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    • pp.25-33
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    • 2023
  • Objective This study aimed to confirm the effect of Sabaek-san extract on the recovery of skin damage in atopic dermatitis-induced mice. Methods In this study, we used 4-week-old NC/Nga mice that were assigned to four groups: control (Ctrl), lipid barrier elimination (LBEG), dexamethasone (Dx) administration after lipid barrier elimination (DxAG), and Sabaek-san extract administration after lipid barrier elimination (SBAG). Ten rats were assigned to each treatment group. After drug administration for 3 days following lipid barrier elimination, ceramide kinase, caspase 14, sodium hydrogen antiporter (NHE), cathelicidin, claudin, and Toll-like receptor (TLR2) were observed to confirm restoration of skin moisturizer production, antimicrobial barriers, and tight junctions in the skin barrier. Results Ceramide kinase and caspase 14 positive reactions were significantly higher in the SBAG group than in the LBEG or DxAG groups. NHE and cathelicidin showed a higher positive reaction in the SBAG group than in the LBEG and DxAG groups. Claudins and TLR2 showed a higher positive reaction in the SBAG group than in the LBEG or DxAG groups. Conclusion It was confirmed that Sabaek-san extract may have the potential to restore damaged skin barrier in atopic dermatitis.

Clostridium difficile Toxin A Inhibits Erythropoietin Receptor-Mediated Colonocyte Focal Adhesion Through Inactivation of Janus Kinase-2

  • Nam, Seung Taek;Seok, Heon;Kim, Dae Hong;Nam, Hyo Jung;Kang, Jin Ku;Eom, Jang Hyun;Lee, Min Bum;Kim, Sung Kuk;Park, Mi Jung;Chang, Jong Soo;Ha, Eun-Mi;Shong, Ko Eun;Hwang, Jae Sam;Kim, Ho
    • Journal of Microbiology and Biotechnology
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    • v.22 no.12
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    • pp.1629-1635
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    • 2012
  • Previously, we demonstrated that the erythropoietin receptor (EpoR) is present on fibroblasts, where it regulates focal contact. Here, we assessed whether this action of EpoR is involved in the reduced cell adhesion observed in colonocytes exposed to Clostridium difficile toxin A. EpoR was present and functionally active in cells of the human colonic epithelial cell line HT29 and epithelial cells of human colon tissues. Toxin A significantly decreased activating phosphorylations of EpoR and its downstream signaling molecules JAK-2 (Janus kinase 2) and STAT5 (signal transducer and activator of transcription 5). In vitro kinase assays confirmed that toxin A inhibited JAK 2 kinase activity. Pharmacological inhibition of JAK2 (with AG490) abrogated activating phosphorylations of EpoR and also decreased focal contacts in association with inactivation of paxillin, an essential focal adhesion molecule. In addition, AG490 treatment significantly decreased expression of occludin (a tight junction molecule) and tight junction levels. Taken together, these data suggest that inhibition of JAK2 by toxin A in colonocytes causes inactivation of EpoR, thereby enhancing the inhibition of focal contact formation and loss of tight junctions known to be associated with the enzymatic activity of toxin A.

Expression of Neurotrophic Factors, Tight Junction Proteins, and Cytokines According to the Irritable Bowel Syndrome Subtype and Sex

  • Lee, Ju Yup;Kim, Nayoung;Park, Ji Hyun;Nam, Ryoung Hee;Lee, Sun Min;Song, Chin-Hee;Kim, Geun;Na, Hee Young;Choi, Yoon Jin;Kim, Jin Joo;Lee, Dong Ho
    • Journal of Neurogastroenterology and Motility
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    • v.26 no.1
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    • pp.106-116
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    • 2020
  • Background/Aims Emerging evidence shows that the mechanism of irritable bowel syndrome (IBS) is associated with neurotrophic factors and tight junction proteins (TJPs). It is known that there are sex differences in the pathophysiology of IBS. The aim of the present study is to determine expression levels of neurotrophic factors, TJPs, and cytokines according to IBS subtype and sex. Methods From 59 IBS (33 IBS-constipation, 21 IBS-diarrhea, and 5 IBS-mixed) and 36 control patients, colonic mucosa mRNA expression levels of transient receptor potential vanilloid-1 (TRPV1), nerve growth factor (NGF), glial cell-derived neurotrophic factor (GDNF), and various TJPs were assessed by real-time polymerase chain reaction. Western blot was performed to determine levels of zonular occludens-1 (ZO-1). Serum levels of cytokines were measured by enzyme-linked immunosorbent assay. Results TRPV1, GDNF, and NGF mRNA levels were significantly increased in those with IBS-constipation compared to those in controls (all P < 0.05). However, they showed no significant difference between those with IBS-diarrhea and controls. Expression level of TRPV1 correlated with that of GDNF (r = 0.741, P < 0.001) and NGF (r = 0.935, P < 0.001). ZO-1 RNA expression levels were lower (P = 0.021) in female IBS-diarrhea than those in controls, although they showed no significant differences between male IBS-diarrhea and controls. Serum IL-1β levels in female IBS were significantly higher than those of male IBS, especially in IBS-constipation (P < 0.001). Conclusion Our results suggest that neurotrophic factors and IL-1β are closely related to IBS-constipation and that decrease of ZO-1 is an important factor in female with IBS-diarrhea.