scholarly journals Mice Deficient in Cyp4a14 Have An Increased Number of Goblet Cells and Attenuated Dextran Sulfate Sodium-Induced Colitis

2018 ◽  
Vol 50 (6) ◽  
pp. 2272-2282 ◽  
Author(s):  
Qingxia Xuan ◽  
Yunfeng Zhou ◽  
Binbin Tan ◽  
Zhongyue Xiao ◽  
Shizhen Dong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Quantitative Polymerase Chain Reaction ◽  
Periodic Acid ◽  
Mucosal Injury ◽  
Goblet Cells ◽  
Mrna Levels ◽  
Periodic Acid Schiff ◽  
Monooxygenase Activity

Background/Aims: Cyp4a14 is a member of cytochrome P450 (Cyp450) enzyme superfamily that possesses NADPH monooxygenase activity, which catalyzes omega-hydroxylation of medium-chain fatty acids and arachidonic acid. Study suggests that down-regulation of Cyp4a14 has an anti-inflammatory response in intestine. The present study was to test the function of Cyp4a14 in dextran sulfate sodium (DSS)-induced colitis. Methods: Female Cyp4a14-knockout (KO) and wild-type (WT) mice were treated with DSS for 6 days to induce colitis. The colon of mice was histologically observed by hematoxylin and eosin (H&E) and periodic acid Schiff (PAS) staining. The serum malondialdehyde (MDA), an endogenous indicator of oxidative stress, was chemically measured. Proinflammatory and NADPH oxidase genes were examined by quantitative polymerase chain reaction (qPCR). Results: Cyp4a14-KO mice had a significantly higher number of goblet cells in the colon and were more resistant to DSS-induced colitis compared with the WT mice. The DSS-treated KO mice had lower levels of MDA. Consistent with the milder inflammatory pathological changes, DSS-treated KO mice had lower levels of IL-1β, IL-6 and TNF-α mRNA in the liver and the colon. Moreover, the colon of DSS-treated Cyp4a14-KO and WT mice had higher mRNA levels of two members of NADPH oxidases, Nox2 and Nox4, suggesting that both Nox2 and Nox4 are inflammatory markers. By contrast, DSS-treated WT and KO mice had drastically decreased epithelium-localized Nox1 and dual oxidase (Duox) 2 mRNA levels, coinciding with the erosion of the mucosa induced by DSS. Conclusion: These results suggests a hypothesis that the increased goblet cell in the colon of Cyp4a14-KO mice provides protection from mucosal injury and Cyp4a14-increased oxidative stress exacerbates DSS-induced colitis. Therefore, Cyp4a14 may represent a potential target for treating colitis.

scholarly journals Oral Dextran Sulfate Sodium Administration Induces Peripheral Spondyloarthritis Features in SKG Mice Accompanied by Intestinal Bacterial Translocation and Systemic Th1 and Th17 Cell Activation.

2021 ◽  
Author(s):  
Yuya Tabuchi ◽  
Masao Katsushima ◽  
Yuri Nishida ◽  
Mirei Shirakashi ◽  
Hideaki Tsuji ◽  
...  
Keyword(s):  
Bacterial Translocation ◽  
Whole Blood ◽  
Th17 Cell ◽  
Cell Activation ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Quantitative Polymerase Chain Reaction ◽  
Bacterial Species ◽  
Bacterial Dna ◽  
Anti Fungal

Abstract Background: Spondyloarthritis (SpA) is an autoimmune and autoinflammatory musculoskeletal disease characterised by systemic enthesitis. Recent research has focused on subclinical inflammatory bowel disease (IBD) in SpA pathogenesis. SKG mice, harbouring the Zap70 W163C mutation, increase autoreactive Th17 cells intrinsically, and show SpA features, including enteritis, after peritoneal injection of β-1,3- glucan under SPF conditions. In a conventional environment, they exhibit spontaneous arthritis with fungal factors. This study aimed to clarify whether oral dextran sulfate sodium (DSS) administration, utilised in IBD model mice, can provoke SpA features in SKG mice under SPF conditions, focusing on the relationship between gut microorganisms and SpA pathogenesis.Methods: SKG and BALB/c mice were administered oral DSS, and their body weights, arthritis, and enthesitis scores were recorded. In another cohorts, antibiotics (meropenem and vancomycin) or an anti-fungal agent (amphotericin B) were administered orally before DSS administration. The splenic Th1 and Th17 cell populations were examined before and after DSS administration using flow cytometry. Furthermore, the amount of circulating bacterial DNA in whole blood was measured by absolute quantitative polymerase chain reaction (qPCR), and the number and characteristics of bacterial species corresponding to these circulating DNA were analised by next-generation sequencing (NGS).Results: Ankle enthesitis as a peripheral SpA feature was elicited in half of DSS-administered SKG mice, and none of the BALB/c mice. Pre-administration of antibiotics suppressed enthesitis, whilst an anti-fungal agent could not. Th1 and Th17 cell levels in the spleen increased after DSS administration, and this was suppressed by pre-administration of antibiotics. SKG mice have a larger amount of bacterial DNA in whole blood than BALB/c mice before and one day after the initiation of DSS administration. The number of bacterial species in whole blood increased after DSS administration in SKG and BALB/c mice. Some genera and species significantly specific to the DSS-treated SKG mice group were also detected. Conclusion: Oral DSS administration alone elicited peripheral enthesitis in SKG mice with bacterial translocation accompanied by increased splenic Th1 and Th17 cell levels. Pre-administration of antibiotics ameliorated these DSS-induced SpA features. These findings suggest that intestinal bacterial leakage plays a pivotal role in SpA pathogenesis.

The expulsion of Echinostoma trivolvis from C3H Mice: differences in glycoconjugates in mouse versus hamster small intestinal mucosa during infection

1996 ◽  
Vol 70 (2) ◽  
pp. 115-121 ◽  
Author(s):  
T. Fujino ◽  
B. Fried
Keyword(s):  
Lectin Binding ◽  
Periodic Acid ◽  
Helix Pomatia ◽  
Goblet Cells ◽  
Small Intestinal Mucosa ◽  
Periodic Acid Schiff ◽  
C3h Mice ◽  
Small Intestines ◽  
Echinostoma Trivolvis ◽  
Lectin Binding Sites

AbstractMucosal glycoconjugates were examined in C3H mice and in hamster small intestines infected with Echinostoma trivolvis and in uninfected rodents, using periodic-acid Schiff (PAS) and high-iron diamine-alcian blue (HID-AB) staining and three different fluorescein-conjugated lectins: Triticum vulgaris agglutinin (WGA), Helix pomatia agglutinin (HPA) and Griffonia simplicifolia agglutinin (GSA-II). Lectin-labelling by electron microscopy was also undertaken with WGA and HPA lectin-gold probes. HID-AB stain demonstrated that the most mature goblet cells of the mouse villi contain sulfomucins, whereas those of hamsters contain sialomucins. The expression of lectin-binding sites and the intensity of the lectin binding in the small intestines were changed by echinostome infection. Specific differences in the reaction to mucin glycoproteins were clearly observed between the mouse and hamster intestines infected with E. trivolvis; lectin-binding to hyperplastic goblet cells and crypts in the infected mice increased, while no marked increase in the number of goblet cells and reaction to the glycoconjugates were observed in the infected hamsters. These findings indicate that the expression of terminal N-acetyl-D-galactosamine, sialic acid and N-acetyl-D-glucosamine increased in mucins secreted from hyperplastic goblet cells associated with E. trivolvis infection in mice. No marked increase in these glycoconjugates occurred in hamster infections. These findings reflect clear differences in infectivity of E. trivolvis in C3H mice versus hamsters.

Alterations in Muc2 biosynthesis and secretion during dextran sulfate sodium-induced colitis

2002 ◽  
Vol 282 (2) ◽  
pp. G382-G389 ◽  
Author(s):  
Ingrid B. Renes ◽  
Jos A. Boshuizen ◽  
Daniëlle J. P. M. Van Nispen ◽  
Nathalie P. Bulsing ◽  
Hans A. Büller ◽  
...  
Keyword(s):  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Cell Loss ◽  
Distal Colon ◽  
Proximal Colon ◽  
Histological Evaluation ◽  
Mrna Levels ◽  
Precursor Synthesis ◽  
Regenerative Phase ◽  
Active Disease

To gain insight into mucin 2 (Muc2) synthesis and secretion during dextran sulfate sodium (DSS)-induced colitis, rats were treated with DSS for 7 days. Colonic segments were excised on days 0 (control), 2 (onset of disease), 7 (active disease), and 14(regenerative phase) for histological evaluation. Explants were metabolically labeled with 35S-labeled amino acids or [35S]sulfate followed by chase incubation. Homogenates were analyzed by SDS-PAGE and 35S-labeled Muc2 was quantified. Also, total Muc2 protein and mRNA were quantified. DSS-induced crypt loss, ulcerations, and concomitant goblet cell loss were most pronounced in the distal colon. Muc2 precursor synthesis increased progressively in the proximal colon but was unaltered in the distal colon during onset and active disease. During the regenerative phase, Muc2 precursor synthesis levels normalized in the proximal colon but increased in the distal colon. Total Muc2 levels paralleled the changes seen in Muc2 precursor synthesis levels. During each disease phase, total Muc2 secretion was unaltered in the proximal and distal colon. [35S]sulfate incorporation into Muc2 only decreased in the proximal colon during active disease and the regenerative phase, whereas secretion of [35S]sulfate-labeled Muc2 increased. During the regenerative phase, Muc2 mRNA levels were downregulated in both colonic segments. In conclusion, DSS-induced loss of goblet cells was accompanied by an increase or maintenance of Muc2 precursor synthesis, total Muc2 levels, and Muc2 secretion. In the proximal colon, Muc2 became undersulfated, whereas sulfated Muc2 was preferentially secreted. Collectively, these data suggest specific adaptations of the mucus layer to maintain the protective capacities during DSS-induced colitis.

A physiological, biochemical and histological study of goose tracheal mucin and its secretion

1977 ◽  
Vol 279 (969) ◽  
pp. 513-540 ◽  
Keyword(s):  
Sialic Acid ◽  
Nerve Stimulation ◽  
Histological Study ◽  
Periodic Acid ◽  
Gel Filtration ◽  
Goblet Cells ◽  
Mucin Secretion ◽  
Electron Microscopic ◽  
Periodic Acid Schiff ◽  
Tracheal Mucus

Tracheal mucin secretion has been measured from a segment of trachea, isolated in situ , in anaesthetized geese by a method that involves radioactive labelling of tracheal mucus glycoproteins (Gallagher et al. 1975). Goose tracheal mucus comes entirely from goblet cells, since the goose trachea does not contain submucosal mucous or serous glands, and this method has been used to investigate the nervous and pharmacological control of the mucin secretion from these epithelial goblet cells. The mucins secreted have been collected, fractionated, and chemically analysed. Intracellular mucin has been examined histochemically, and the results of electron microscopic observations of epithelial cells and nerves are presented. Acetylcholine increased tracheal mucin secretion, and this effect was completely blocked by atropine. Neither α- nor β-stimulant sympathomimetic amines affected tracheal mucin secretion. Stimulation of the peripheral cut ends of the descending oesophageal nerves increased tracheal mucin secretion and the majority of this response, approximately three-quarters, appeared to be cholinergic since this proportion was blocked by atropine. The mediator for the atropine-resistant part of the response is not known, but it appears not to be a β-adrenoreceptor stimulant since the response to nerve stimulation was unaffected by propranolol given at 34 μm intrasegmentally. Other possibilities are discussed. Atropine itself decreased the resting level of tracheal mucin secretion. The local anaesthetic, lignocaine, increased tracheal mucin secretion, while at the same time blocking the responses to acetylcholine and descending oesophageal nerve stimulation. The implications of this are discussed. The electrophoretic, gel filtration and ion-exchange properties of goose tracheal mucins showed that they represented high molecular mass, negatively charged glycoproteins which could be labelled biosynthetically with [ 35 S]sulphate, [ 3 H]- and [ 14 C]glucose. These mucins could be stained with Alcian blue or periodic acid Schiff reagent. The carbohydrate composition was unusual for an epithelial glycoprotein in that fucose was absent and mannose was present in small quantities. The monosaccharides present in larger quantity were galactose, N -acetylglucosamine, N -acetylgalactosamine and sialic acid. Histochemical analysis of tissue sections of gosling tracheas demonstrated that nearly all of the glycoprotein in epithelial goblet cells contained both sialic acid and sulphate residues. Sialated mucin was present also, but to a lesser extent, and many cells contained a mixture of sialated and sulphated mucins. The adult goose trachea had a high proportion of sialated glycoprotein. Electron microscopy showed a range of epithelial cell types and intra-epithelial nerves also. Many of the nerves had neurosecretory vesicles suggestive of motor function and some were near to goblet cells.

scholarly journals Histochemical reactivity of peanut lectin-horseradish peroxidase conjugate.

1980 ◽  
Vol 28 (9) ◽  
pp. 979-990 ◽  
Author(s):  
P J Stoward ◽  
S S Spicer ◽  
R L Miller
Keyword(s):  
Sialic Acid ◽  
Horseradish Peroxidase ◽  
Periodic Acid ◽  
Apical Cell ◽  
Goblet Cells ◽  
Surface Epithelium ◽  
Renal Tubules ◽  
Peanut Lectin ◽  
Periodic Acid Schiff ◽  
Terminal Galactose

A peanut lectin-horseradish peroxidase (PL-HRP) conjugate has been applied to histochemical staining of paraffin sections of various mouse organs. The PL-HRP conjugate has selectively reacted with secretory bodies, the Golgi zone, and the apical cell surface in various cell types. Some positive sites, including lingual and tracheal serous glands, Brunner's glands, and the brush border of the proximal straight nephron, contained periodic acid-Schiff (PAS)-positive glycoconjugate with no affinity for basic reagents. The stored secretion in these sites was interpreted as containing neutral glycoprotein with terminal galactose residues which could, in part at least, account for the PAS reactivity. Duodenal goblet cells, which exhibited basophilia attributable to sulfate esters, also bound PL-HRP. As the binding was affected by prior sialidase digestion, the secretory glycoprotein in the duodenal goblet cells was judged to contain oligosaccharides with sulfate esters and terminal galactose uncapped by sialic acid. All sites known from their basophilia to form sialomucin failed to stain with the PL-HRP conjugate, but consistently gained reactivity following sialidase digestion and were inferred, therefore, to possess glycoproteins with oligosaccharide side chains containing subterminal galactose and terminal sialic acid. Lingual mucous glands, known to secrete a mucosubstance with basophilic properties indicative of the presence of sulfate esters but not sialic acid, stained with PL-HRP only after sialidase digestion and, accordingly, were reinterpreted as containing both sulfate esters and terminal galactose-sialic acid dimers. Staining of gastric surface epithelium demonstrated a srongly PAS-reactive neutral glycoprotein, and that of goblet cells in the cecum disclosed PAS-positive sulfated glycoprotein. The latter two sites lacked PL-HRP affinity without or with prior sialidase treatment and apparently possessed neither terminal galactose residues nor galactose-sialic acid dimers. PL-HRP affinity was observed exclusively in the Golgi cisternae of some epithelial cells, thus indicating that galactose occurs transiently as a terminal residue in this site. A few histologic sites, such as pancreatic and gastric zymogen cells and renal tubules, were devoid of both PAS reactivity and basophilia indicative of the presence of complex carbohydrate but stained strongly with the PL-HRP conjugate by means which are not understood. Galactose in the PL-HRP solution blocked or reversed the PL-HRP binding in most of the structures with an affinity for the conjugate, supporting the conclusions that the reagent is specific for galactosyl residues.

Preventive effect of carob (Ceratonia siliqua L.) in dextran sulfate sodium-induced ulcerative colitis in rat

RSC Advances ◽  
2016 ◽  
Vol 6 (24) ◽  
pp. 19992-20000 ◽  
Author(s):  
Kaïs Rtibi ◽  
Mohamed-Amine Jabri ◽  
Slimen Selmi ◽  
Hichem Sebai ◽  
Jean-Claude Marie ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ulcerative Colitis ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Gastrointestinal Diseases ◽  
Common Mechanism ◽  
Ceratonia Siliqua ◽  
Preventive Effect ◽  
Ceratonia Siliqua L ◽  
And Oxidative Stress

Inflammation and oxidative stress are a common mechanism of many gastrointestinal diseases such ulcerative colitis.

scholarly journals APicrorhiza kurroaDerivative, Picroliv, Attenuates the Development of Dextran-Sulfate-Sodium-Induced Colitis in Mice

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
De-Kui Zhang ◽  
Jian-Jie Yu ◽  
Yu-Min Li ◽  
Li-Na Wei ◽  
Yi Yu ◽  
...  
Keyword(s):  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Activity Index ◽  
Quantitative Polymerase Chain Reaction ◽  
Critical Role ◽  
Disease Activity Index ◽  
Enzyme Linked Immunosorbent Assay ◽  
Histological Score ◽  
Polymerase Chain ◽  
Histology Score

Background. Free radicals and proinflammatory cytokines have been shown to play a critical role in the pathogenesis of ulcerative colitis (UC). Picroliv, aPicrorhiza kurroaderivative, has been demonstrated to have antioxidant and anti-inflammatory effect. The purpose of the study was to investigate the effects of picroliv on experimental model of UC in mice.Materials and Methods. Picroliv was administrated orally by gavage to mice with colitis induced by dextran sulfate sodium (DSS). Disease activity index (DAI), colon length, and histology score were observed. Myeloperoxidase (MPO) activity, and SOD, MDA concentrations were measured by enzyme-linked immunosorbent assay (ELISA) while the expression of cytokine mRNAs was studied by real-time-quantitative polymerase chain reaction and also ELISA. The expression of NF-κB p65 was observed by immunohistochemistry staining and western blotting.Results. A significant improvement was observed in DAI and histological score in mice treated with picroliv, and incerased MPO activity, MDA concentrations, and the expression of IL-1β, TNF-α, and NF-κB p65 in mice with DSS-induced colitis were significantly reduced while decreased SOD level increased following administration of picroliv.Conclusion. The administration of picroliv leads to an amelioration of DSS-induced colitis, suggesting administration of picroliv may provide a therapeutic approach for UC.

scholarly journals Loss of NHE8 expression impairs intestinal mucosal integrity

2015 ◽  
Vol 309 (11) ◽  
pp. G855-G864 ◽  
Author(s):  
Aiping Wang ◽  
Jing Li ◽  
Yang Zhao ◽  
Malin E. V. Johansson ◽  
Hua Xu ◽  
...  
Keyword(s):  
Periodic Acid ◽  
Paneth Cell ◽  
Distal Colon ◽  
Goblet Cells ◽  
Paneth Cells ◽  
Wild Type ◽  
Periodic Acid Schiff ◽  
Mucin Production ◽  
Mucosal Integrity ◽  
Mucin 2

The newest member of the Na+/H+ exchanger (NHE) family, NHE8, is abundantly expressed at the apical membrane of the intestinal epithelia. We previously reported that mucin 2 expression was significantly decreased in the colon in NHE8−/− mice, suggesting that NHE8 is involved in intestinal mucosal protection. In this study, we further evaluated the role of NHE8 in intestinal epithelial protection after dextran sodium sulfate (DSS) challenge. Compared with wild-type mice, NHE8−/− mice have increased bacterial adhesion and inflammation, especially in the distal colon. NHE8−/− mice are also susceptible to DSS treatment. Real-time PCR detected a remarkable increase in the expression of IL-1β, IL-6, TNF-α, and IL-4 in DSS-treated NHE8−/− mice compared with DSS-treated wild-type littermates. Immunohistochemistry showed a disorganized epithelial layer in the colon of NHE8−/− mice. Periodic acid-Schiff staining showed a reduction in the number of mature goblet cells and the area of the goblet cell theca in NHE8−/− mice. Phyloxine/tartrazine staining revealed a decrease in functional Paneth cell population in the NHE8−/− small intestinal crypt. The expression of enteric defensins was also decreased in NHE8−/− mice. The reduced mucin production in goblet cells and antimicrobial peptides production in Paneth cells lead to disruption of the intestinal mucosa protection. Therefore, NHE8 may be involved in the establishment of intestinal mucosal integrity by regulating the functions of goblet and Paneth cells.

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