• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.2235-2245
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• 2016

Ulcerative colitis (UC) results from colonic epithelial barrier defects and impaired mucosal immune responses. In this study, we aimed to investigate the modifying effects of a Spirogyra neglecta extract (SNE), a polysaccharide extract (PE) and a chloroform fraction (CF) on dextran sodium sulfate (DSS)-induced colitis in mice and to determine the mechanisms. To induce colitis, ICR mice received 3% DSS in their drinking water for 7 days. Seven days preceding the DSS treatment, oral administration of SNE, PE and CF at doses of 50, 25 and 0.25 mg/kg body weight (low dose), 200, 100 and 1 mg/kg body weight (high dose) and vehicle was started and continued for 14 days. Histologic findings showed that DSS-induced damage of colonic epithelial structure and inflammation was attenuated in mice pre-treated with SNE, PE and CF. Furthermore, SNE and PE significantly protected colonic epithelial cells from DSS-induced cell cycle arrest, while SNE, PE and CF significantly diminished apoptosis. Proteome analysis demonstrated that SNE and PE might ameliorate DSS-induced colitis by inducing antioxidant enzymes, restoring impaired mitochondria function, and regulating inflammatory cytokines, proliferation and apoptosis. These results suggest that SNE and PE could prevent DSS-induced colitis in ICR mice by protection against and/or aiding recovery from damage to the colonic epithelium, reducing ROS and maintaining normal mitochondrial function and apoptosis.

• Food Science and Biotechnology
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• v.16 no.4
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• pp.605-609
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• 2007

The effects of lactic acid fermented yam yogurt (Yam/YG) on colon mucosal tissue were investigated in a loperamide-induced constipation rat models. Sprague-Dawley rats were fed for 6 weeks with 3 types of diets (normal, supplemented with lactic acid bacteria, and supplemented with Yam/YG), and were then administered loperamide intraperitoneally twice daily for 5 days. Administration of loperamide decreased fecal excretion and the moisture content of feces with increasing of numbers of pellets in the colon. On the histopathologic findings from hematoxylin and eosin (H& E) and alcian blue stainings, supplementation with Yam/YG resulted in the recovery of depleted goblet cells and mucin, and increased the numbers of Ki-67 positive cells, indicating restoration of colonic mucosa through cell proliferation and crypt regeneration against damages observed in crypt epithelial cells of loperamide-induced rats. These results indicate that Yam/YG improves evacuation and mucus production in the gastrointestinal tracts of constipated-induced rats.

• Natural Product Sciences
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• v.12 no.1
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• pp.38-43
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• 2006

Ilekudinol B is one of the flavonoids isolated from Weigela subsessilis (Caprifoliaceae). In the present study, the suppression effect of ilekudinol B on tumor necrosis factor $(TNF)-{\alpha}-induced$ cyclooxygenase-2 (COX-2) expression was investigated in human colon epithelial cell line HT-29. Interleukin-8 (IL-8) production and prostaglandin $E_2\;(PGE_2)$ secretion was measured by enzyme-linked immunosorbent assay (ELISA). COX-2 and nuclear factor $(NF)-{\kappa}B$ expression were determined by Western blot analysis. Ilekudinol B significantly inhibited $TNF-{\alpha}-induced$ secretion of IL-8 and prostaglandin $E_2\;(PGE_2)$ from the human colon epithelial cell line HT-29 in a concentration-dependent manner. In addition, ilekudinol B remarkably diminished $TNF-{\alpha}-induced$ COX-2 expression and $NF-{\kappa}B$ p65 subunit translocation to the nucleus. In conclusion, our results indicate that ilekudinol B may have anti-inflammatory activity on $TNF-{\alpha}-dependent$ colonic inflammation.

• Proceedings of the PSK Conference
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• 2005.11a
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• pp.231-232
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• 2005

Bacteria of Shigella spp. are responsible for shigellosis in humans, a disease characterized by destruction of the colonic epithelium that is induced by the inflammatory response elicited by invasive bacteria. They use a type III secretion system injecting effector proteins into host cells to induce their entry into epithelial cells and triggers apoptosis in macrophages. We present evidence that the effector OspG is a protein kinase that binds various ubiquitinylated ubiquitin-conjugating enzymes (E2s) and blocks degradation of phospho-$I{\kappa}B{\alpha}$ induced upon entry of bacteria into epithelial cells. Transfection experiments confirmed that OspG interferes with the $NF-{\kappa}B$ activation patway by preventing phospho-$I{\kappa}B{\alpha}$ degradation, suggesting that OspG inactivates a component of the $SCF^{{\beta}-TrCP}$ ubiquitin ligase complex (E3) involved in phospho-$I{\kappa}B{\alpha}$ ubiquitination. Upon infection of ileal loops in rabbits, the ospG mutant induced a stronger inflammatory response compared with the wild-type strain, indicating that OspG down-regulates the host innate response induced by invasive bacteria.

• BMB Reports
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• v.47 no.9
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• pp.494-499
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• 2014

NADH:quinone oxidoreductase 1 (NQO1) is known to be involved in the regulation of energy synthesis and metabolism, and the functional studies of NQO1 have largely focused on metabolic disorders. Here, we show for the first time that compared to NQO1-WT mice, NQO1-KO mice exhibited a marked increase of permeability and spontaneous inflammation in the gut. In the DSS-induced colitis model, NQO1-KO mice showed more severe inflammatory responses than NQO1-WT mice. Interestingly, the transcript levels of claudin and occludin, the major tight junction molecules of gut epithelial cells, were significantly decreased in NQO1-KO mice. The colons of NQO1-KO mice also showed high levels of reactive oxygen species (ROS) and histone deacetylase (HDAC) activity, which are known to affect transcriptional regulation. Taken together, these novel findings indicate that NQO1 contributes to the barrier function of gut epithelial cells by regulating the transcription of tight junction molecules.

• Korean Journal of Clinical Laboratory Science
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• v.55 no.1
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• pp.37-44
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• 2023

Enterotoxigenic Bacteroides fragilis (ETBF) has been reported to promote colitis and colon cancer through the secretion of B. fragilis toxin (BFT), a zinc-dependent metalloprotease. In colonic epithelial cells, BFT induces the cleavage of E-cadherin into the 80 kDa ectodomain and the 33 kDa membrane-bound intracellular domain. The resulting membrane-tethered fragment is then cleaved by γ-secretase forming the 28 kDa E-cadherin intracellular fragment. The 28 kDa cytoplasmic fragment is then degraded by an unknown mechanism. In this study, we found that the 28 kDa E-cadherin intracellular fragment was degraded by the proteasome complex. In addition, we found that this sequential E-cadherin cleavage mechanism is found not only in colonic epithelial cells but also in the human breast cancer cell line, BT-474. Finally, we report that staurosporine also induces E-cadherin cleavage in the human breast cancer cell line, MCF7, through γ-secretase. However, further degradation of the 28 kDa E-cadherin intracellular domain is not dependent on the proteasome complex. These results suggest that the BFT-induced E-cadherin cleavage mechanism is conserved in both colonic and breast cancer cells. This observation indicates that ETBF may also play a role in the carcinogenesis of tissues other than the colon.

• Journal of Microbiology and Biotechnology
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• v.29 no.10
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• pp.1675-1681
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• 2019

Clostridium difficile toxin A is known to cause colonic epithelial cell apoptosis, which is considered the main causative event that triggers inflammatory responses in the colon, reflecting the concept that the essential role of epithelial cells in the colon is to form a physical barrier in the gut. We previously showed that toxin A-induced colonocyte apoptosis and subsequent inflammation were dependent on prostaglandin E2 ($PGE_2$) produced in response to toxin A stimulation. However, the molecular mechanism by which $PGE_2$ mediates cell apoptosis in toxin A-exposed colonocytes has remained unclear. Here, we sought to identify the signaling pathway involved in toxin A-induced, $PGE_2$-mediated colonocyte apoptosis. In non-transformed NCM460 human colonocytes, toxin A exposure strongly upregulated expression of Bak, which is known to form mitochondrial outer membrane pores, resulting in apoptosis. RT-PCR analyses revealed that this increase in Bak expression was attributable to toxin A-induced transcriptional upregulation. We also found that toxin A upregulation of Bak expression was dependent on $PGE_2$ production, and further showed that this effect was recapitulated by an Prostaglandin E2(PGE2) receptor-1 receptor agonist, but not by agonists of other EP receptors. Collectively, these results suggest that toxin A-induced cell apoptosis involves $PGE_2$-upregulation of Bak through the EP1 receptor.

• Journal of Life Science
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• v.28 no.9
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• pp.1016-1021
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• 2018

Clostridium difficile toxin A causes pseudomembranous colitis. The pathogenesis of toxin A-induced colonic inflammation includes toxin A-dependent epithelial cell apoptosis, resulting in the loss of barrier function provided by epithelial cells against luminal pathogens. Toxin A-dependent epithelial cell apoptosis has been linked to toxin A-induced production of reaction oxygen species and subsequent p38MAPK activation; $p21^{CIP1/WAF1}$ upregulation-dependent cell cycle arrest; cytoskeletal disaggregation; and/or the induction of Fas ligand on epithelial cells. However, the molecular mechanisms underlying toxin A-induced apoptosis remain poorly understood. This study tested whether toxin A could block the Wnt signaling pathway, which is involved in gut epithelial cell proliferation, differentiation and antiapoptotic progression. Toxin A treatment of nontransformed human colonocytes (NCM460) rapidly reduced ${\beta}$-catenin protein, an essential component of the Wnt signaling pathway. Exposure of mouse ileum to toxin A also significantly reduced ${\beta}$-catenin protein levels. MG132 inhibition of proteasome-dependent protein degradation resulted in the recovery of toxin A-mediated reduction of ${\beta}$-catenin, indicating that toxin A may activate intracellular processes, such as $GSK3{\beta}$, to promote degradation of ${\beta}$-catenin. Immunoblot analysis showed that toxin A increased active phosphorylation of $GSK3{\beta}$. Because the Wnt signaling pathway is essential for gut epithelial cell proliferation and anti-apoptotic processes, our results suggest that toxin A-mediated inhibition of the Wnt signaling pathway may be required for maximal toxin A-induced apoptosis of gut epithelial cells.

• The Journal of Internal Korean Medicine
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• v.38 no.6
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• pp.863-876
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• 2017

Objectives: The aim of this experimental study was to evaluate the anti-neoplastic and anti-inflammatory effects of single and mixed extracts of Ulmus davidiana (UD) and Oldenlandia diffusa (OD) on azoxymethane/dextran sodium sulfate (AOM/DSS)-induced colonic neoplasms in mice. Methods: AOM/DSS induces colitis-associated colonic neoplasms in mice. Mice were divided into seven groups: normal-no inducement and no treatment; control-colonic neoplasms with no treatment; UD-colonic neoplasms and treatment with UD; OD-colonic neoplasms and treatment with OD; UD1+OD1-colonic neoplasms and treatment with UD1 and OD1. UD1+OD2-colonic neoplasms and treatment with UD1 and OD2; UD2+OD1-colonic neoplasms and treatment with UD2 and OD1. Single and mixed preparations of UD and OD were applied to mice for six weeks. The colon length and weight and histopathologic changes of colon tissue were observed. Serum pro-inflammatory cytokines, including tumor necrosis factor-alpha ($TNF-{\alpha}$) and interleukin-6 (IL-6), were determined by enzyme-linked immunosorbent assay. The mRNA expression levels of Bax, Bcl-2, and interferon-gamma ($INF-{\gamma}$) were measured by RT-PCR. Results: The colon length was significantly increased in OD, UD1+OD2, and UD2+OD1 mice, and the colon weight was significantly decreased in OD and UD1+OD2 mice. The morphological change of colon epithelial cells was more suppressed in complex-treatment groups than in single-treatment groups. The inhibitory effect on inflammatory cell invasion was especially shown in UD1+OD2 mice. The serum level of the pro-inflammatory $TNF-{\alpha}$ was decreased in all complex-treatment groups, and the IL-6 level was decreased in UD1+OD1 mice. Single-treatment groups had an increase in the mRNA expression of the pro-apoptosis regulator Bax, and UD2+OD1 decreased the mRNA expression of the anti-apoptosis regulator Bcl-2. The mRNA expression of $INF-{\gamma}$ associated with inflammation was decreased in OD and UD1+OD2 mice. Conclusions: This study suggests that single and mixed extracts of Ulmus davidiana and Oldenlandia diffusa have anti-neoplastic and anti-inflammatory effects on AOM/DSS-induced colonic neoplasms in mice. Therefore, we conclude that UD, OD, and a mixture of UD and OD are potential therapeutic agents for colitis-associated colonic neoplasms.

• Korean Journal of Veterinary Research
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• v.34 no.4
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• pp.805-813
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• 1994

Immunohistochemical study on the intestinal tissues obtained from the 21 pigs of the 14 terms in Korea in which the clinical and epidemiological features had indicated the possible outbreaks of porcine epidemic diarrhea(PED) was performed using the indirect immunofluorescence test and/or the immunoperoxidase method in order to detect PED viral antigens in the infected cells of the intestines, and histopathological features were described as well. By immunohistochemical analysis, PED viral antigens were detected in the epithelial cells covering the small intestinal villi and recognized slightly in the cells lining the colonic surface epithelium as well. Occasional fluorescence was also seen in a few intestinal crypt epithelium. On light microscopy, the piglets with PED showed marked villous atrophy and fusion, and severe enterocyte degeneration and desquamation. On the other hand, the older pigs more than 4 week old age was mild villous atrophy and fusion, severe villous epithelial cell proliferation, and moderate mononuclear cell infiltration.