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Sample records for chemically induced colitis

  1. Interleukin 19 reduces inflammation in chemically induced experimental colitis.

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    Matsuo, Yukiko; Azuma, Yasu-Taka; Kuwamura, Mitsuru; Kuramoto, Nobuyuki; Nishiyama, Kazuhiro; Yoshida, Natsuho; Ikeda, Yoshihito; Fujimoto, Yasuyuki; Nakajima, Hidemitsu; Takeuchi, Tadayoshi

    2015-12-01

    Inflammatory bowel disease results from chronic dysregulation of the mucosal immune system and aberrant activation of both the innate and adaptive immune responses. Interleukin (IL)-19, a member of the IL-10 family, functions as an anti-inflammatory cytokine. Here, we investigated the contribution of IL-19 to intestinal inflammation in a model of T cell-mediated colitis in mice. Inflammatory responses in IL-19-deficient mice were assessed using the 2,4,6-trinitrobenzene sulfonic acid (TNBS) model of acute colitis. IL-19 deficiency aggravated TNBS-induced colitis and compromised intestinal recovery in mice. Additionally, the exacerbation of TNBS-induced colonic inflammation following genetic ablation of IL-19 was accompanied by increased production of interferon-gamma, IL-12 (p40), IL-17, IL-22, and IL-33, and decreased production of IL-4. Moreover, the exacerbation of colitis following IL-19 knockout was also accompanied by increased production of CXCL1, G-CSF and CCL5. Using this model of induced colitis, our results revealed the immunopathological relevance of IL-19 as an anti-inflammatory cytokine in intestinal inflammation in mice.

  2. Effect of exercise on chemically-induced colitis in adiponectin deficient mice

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    Saxena Arpit

    2012-08-01

    Full Text Available Abstract Background Inflammatory bowel diseases are associated with increased adiponectin (APN levels, which may exert pro-inflammatory effects in these individuals. Since habitual exercise may increase APN, the aim of this study was to determine how exercise training affects mice with acute colitis. Methods Male adiponectin knock out (APNKO and wild type (WT mice (C57BL/6 were randomly assigned to 4 different groups: 1 Sedentary (SED; 2 Exercise trained (ET; 3 Sedentary with dextran sodium sulfate (DSS treatment (SED + DSS; and 4 Exercise trained with DSS (ET + DSS. Exercise-trained mice ran at 18 m/min for 60 min, 5d/wk for 4 weeks. Subsequently, the ET + DSS and the SED + DSS mice received 2% DSS in their drinking water for 5 days (d, followed by 5d of regular water. Results The clinical symptoms of acute colitis (diarrhea, stool haemoccult, and weight loss were unaffected by exercise and there was no difference between the APNKO and WT mice (p > 0.05 except on day 39. However, the clinical symptoms of the DSS-treated APNKO mice were worse than WT mice treated with DSS and had increased susceptibility to intestinal inflammation due to increased local STAT3 activation, higher IL-6, TNF-α, IL-1β and IL-10 levels, and as a result had increased intestinal epithelial cell proliferation (p  Conclusions Exercise training may contribute in alleviating the symptoms of acute colitis and APN deficiency may exacerbate the intestinal inflammation in DSS-induced colitis.

  3. Dextran sulfate sodium (DSS)-induced colitis in mice.

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    Chassaing, Benoit; Aitken, Jesse D; Malleshappa, Madhu; Vijay-Kumar, Matam

    2014-02-04

    Inflammatory bowel diseases (IBD), mainly comprising ulcerative colitis and Crohn's Disease, are complex and multifactorial diseases with unknown etiology. For the past 20 years, to study human IBD mechanistically, a number of murine models of colitis have been developed. These models are indispensable tools to decipher underlying mechanisms of IBD pathogenesis as well as to evaluate a number of potential therapeutics. Among various chemically induced colitis models, the dextran sulfate sodium (DSS)-induced colitis model is widely used because of its simplicity and many similarities with human ulcerative colitis. This model has both advantages and disadvantages that must be considered when employed. This protocol describes the DSS-induced colitis model, focusing on details and factors that could affect DSS-induced pathology.

  4. Goniothalamin prevents the development of chemically induced and spontaneous colitis in rodents and induces apoptosis in the HT-29 human colon tumor cell line.

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    Vendramini-Costa, Débora Barbosa; Alcaide, Antonio; Pelizzaro-Rocha, Karin Juliane; Talero, Elena; Ávila-Román, Javier; Garcia-Mauriño, Sofia; Pilli, Ronaldo Aloise; de Carvalho, João Ernesto; Motilva, Virginia

    2016-06-01

    Colon cancer is the third most incident type of cancer worldwide. One of the most important risk factors for colon cancer development are inflammatory bowel diseases (IBD), thus therapies focusing on IBD treatment have great potential to be used in cancer prevention. Nature has been a source of new therapeutic and preventive agents and the racemic form of the styryl-lactone goniothalamin (GTN) has been shown to be a promising antiproliferative agent, with gastroprotective, antinociceptive and anti-inflammatory effects. As inflammation is a well-known tumor promoter, the major goal of this study was to evaluate the therapeutic and preventive potentials of GTN on chemically induced and spontaneous colitis, as well as the cytotoxic effects of GTN on a human colon tumor cell line (HT-29). GTN treatments inhibited TNBS-induced acute and chronic colitis development in Wistar rats, reducing myeloperoxidase levels and inflammatory cells infiltration in the mucosa. In spontaneous-colitis using IL-10 deficient mice (C57BL/6 background), GTN prevented colitis development through downregulation of TNF-α, upregulation of SIRT-1 and inhibition of proliferation (PCNA index), without signs of toxicity after three months of treatment. In HT-29 cells, treatment with 10μM of GTN induced apoptosis by increasing BAX/BCL2, p-JNK1/JNK1, p-P38/P38 ratios as well as through ROS generation. Caspase 8, 9 and 3 activation also occurred, suggesting caspase-dependent apoptotic pathway, culminating in PARP-1 cleavage. Together with previous data, these results show the importance of GTN as a pro-apoptotic, preventive and therapeutic agent for IBD and highlight its potential as a chemopreventive agent for colon cancer.

  5. The flavonoid luteolin worsens chemical-induced colitis in NF-kappaB(EGFP transgenic mice through blockade of NF-kappaB-dependent protective molecules.

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    Thomas Karrasch

    Full Text Available BACKGROUND: The flavonoid luteolin has anti-inflammatory properties both in vivo and in vitro. However, the impact of luteolin on experimental models of colitis is unknown. METHODOLOGY/PRINCIPAL FINDINGS: To address the therapeutic impact of luteolin, NF-kappaB(EGFP transgenic mice were fed a chow diet containing 2% luteolin- or isoflavone-free control chow (AIN-76, and acute colitis was induced using 3% dextran sodium sulfate (DSS. Additionally, development of spontaneous colitis was evaluated in IL-10(-/-;NF-kappaB(EGFP transgenic mice fed 2% luteolin chow diet or control chow diet. Interestingly, NF-kappaB(EGFP transgenic mice exposed to luteolin showed worse DSS-induced colitis (weight loss, histological scores compared to control-fed mice, whereas spontaneous colitis in IL-10(-/-;NF-kappaB(EGFP mice was significantly attenuated. Macroscopic imaging of live resected colon showed enhanced EGFP expression (NF-kappaB activity in luteolin-fed mice as compared to control-fed animals after DSS exposure, while cecal EGFP expression was attenuated in luteolin-fed IL-10(-/- mice. Interestingly, confocal microscopy showed that EGFP positive cells were mostly located in the lamina propria and not in the epithelium. Caspase 3 activation was significantly enhanced whereas COX-2 gene expression was reduced in luteolin-fed, DSS-exposed NF-kappaB(EGFP transgenic mice as assessed by Western blot and immunohistochemical analysis. In vitro, luteolin sensitized colonic epithelial HT29 cells to TNFalpha-induced apoptosis, caspase 3 activation, DNA fragmentation and reduced TNFalpha-induced C-IAP1, C-IAP2 and COX-2 gene expression. CONCLUSIONS/SIGNIFICANCE: We conclude that while luteolin shows beneficial effects on spontaneous colitis, it aggravates DSS-induced experimental colitis by blocking NF-kappaB-dependent protective molecules in enterocytes.

  6. Sonographic and Endoscopic Findings in Cocaine-Induced Ischemic Colitis

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    Leth, Thomas; Wilkens, Rune; Bonderup, Ole Kristian

    2015-01-01

    Cocaine-induced ischemic colitis is a recognized entity. The diagnosis is based on clinical and endoscopic findings. However, diagnostic imaging is helpful in the evaluation of abdominal symptoms and prior studies have suggested specific sonographic findings in ischemic colitis. We report...... sonographic and endoscopic images along with abdominal computed tomography in a case of cocaine-induced ischemic colitis....

  7. Sulphasalazine-Induced Pseudomembranous Colitis

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    Hugh J Freeman

    1991-01-01

    Full Text Available An 18-year-old female with ankylosing spondylitis developed fever, abdominal pain and diarrhea on two occasions after starting sulphasalazine therapy. Flexible sigmoidoscopy revealed pseudomembranous colitis; fecal cultures were positive for Clostridium difficile; and C difficile toxin assay was positive. Despite the frequent use of sulphasalazine in the management of inflammatory bowel disease, this complication has been apparently rare. Clinicians should be wary of the onset of diarrhea in patients receiving sulphasalazine, whether for inflammatory bowel disease or other conditions.

  8. Grim19 Attenuates DSS Induced Colitis in an Animal Model.

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    Kim, Jae-Kyung; Lee, Seung Hoon; Lee, Seon-Young; Kim, Eun-Kyung; Kwon, Jeong-Eun; Seo, Hyeon-Beom; Lee, Han Hee; Lee, Bo-In; Park, Sung-Hwan; Cho, Mi-La

    2016-01-01

    DSS induced colitis is a chronic inflammatory disease characterized by inflammation in the gastrointestinal tract, which destabilizes the gut and induces an uncontrolled immune response. Although DSS induced colitis is generally thought to develop as a result of an abnormally active intestinal immune system, its pathogenesis remains unclear. Gene associated with retinoid interferon induced mortality (Grim) 19 is an endogenous specific inhibitor of STAT3, which regulates the expression of proinflammatory cytokines. In this study, we investigated the influence of GRIM19 in a DSS induced colitis mouse model. We hypothesized that Grim19 would ameliorate DSS induced colitis by altering STAT3 activity and intestinal inflammation. Grim19 ameliorated DSS induced colitis severity and protected intestinal tissue. The expression of STAT3 and proinflammatory cytokines such as IL-1β and TNF-α in colon and lymph nodes was decreased significantly by Grim19. Moreover, DSS induced colitis progression in a Grim19 transgenic mouse line was inhibited in association with a reduction in STAT3 and IL-17 expression. These results suggest that Grim19 attenuates DSS induced colitis by suppressing the excessive inflammatory response mediated by STAT3 activation.

  9. Grim19 Attenuates DSS Induced Colitis in an Animal Model

    Science.gov (United States)

    Kim, Jae-kyung; Lee, Seung Hoon; Lee, Seon-Young; Kim, Eun-Kyung; Kwon, Jeong-Eun; Seo, Hyeon-Beom; Lee, Han Hee; Lee, Bo-In; Park, Sung-Hwan; Cho, Mi-La

    2016-01-01

    DSS induced colitis is a chronic inflammatory disease characterized by inflammation in the gastrointestinal tract, which destabilizes the gut and induces an uncontrolled immune response. Although DSS induced colitis is generally thought to develop as a result of an abnormally active intestinal immune system, its pathogenesis remains unclear. Gene associated with retinoid interferon induced mortality (Grim) 19 is an endogenous specific inhibitor of STAT3, which regulates the expression of proinflammatory cytokines. In this study, we investigated the influence of GRIM19 in a DSS induced colitis mouse model. We hypothesized that Grim19 would ameliorate DSS induced colitis by altering STAT3 activity and intestinal inflammation. Grim19 ameliorated DSS induced colitis severity and protected intestinal tissue. The expression of STAT3 and proinflammatory cytokines such as IL-1β and TNF-α in colon and lymph nodes was decreased significantly by Grim19. Moreover, DSS induced colitis progression in a Grim19 transgenic mouse line was inhibited in association with a reduction in STAT3 and IL-17 expression. These results suggest that Grim19 attenuates DSS induced colitis by suppressing the excessive inflammatory response mediated by STAT3 activation. PMID:27258062

  10. Nicotine alleviates colitis-induced damage in rats via its anti-oxidative activity

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    ÖZDEMİR, Zarife Nigar; TAZEGÜL, Gökhan; Kuru, Pınar; BİLGİN, Şeyda; MENTEŞE, Semih Tiber; ERZIK, Can; Sirvanci, Serap; YEGEN, Berrak C

    2014-01-01

    Objective: Previous studies have demonstrated a higher incidence of ulcerative colitis in non-smokers. We investigated the beneficial effects of nicotine treatment on colitis-induced anxiety and oxidative colonic damage on rats.Materials and Methods: Wistar Albino (250-300 g) rats (n=40) were randomly divided into 5 groups as saline-treated colitis group, nicotine pre-treated colitis group, nicotine post-treated colitis group, continuously nicotine-treated colitis group and control group. Gro...

  11. P2X3 receptors mediate visceral hypersensitivity during acute chemically-induced colitis and in the post-inflammatory phase via different mechanisms of sensitization.

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    Annemie Deiteren

    Full Text Available Experiments using P2X3 knock-out mice or more general P2X receptor antagonists suggest that P2X3 receptors contribute to visceral hypersensitivity. We aimed to investigate the effect of the selective P2X3 antagonist A-317491 on visceral sensitivity under physiological conditions, during acute colitis and in the post-inflammatory phase of colitis.Trinitrobenzene sulphonic-acid colitis was monitored by colonoscopy: on day 3 to confirm the presence of colitis and then every 4 days, starting from day 10, to monitor convalescence and determine the exact timepoint of endoscopic healing in each rat. Visceral sensitivity was assessed by quantifying visceromotor responses to colorectal distension in controls, rats with acute colitis and post-colitis rats. A-317491 was administered 30 min prior to visceral sensitivity testing. Expression of P2X3 receptors (RT-PCR and immunohistochemistry and the intracellular signalling molecules cdk5, csk and CASK (RT-PCR were quantified in colonic tissue and dorsal root ganglia. ATP release in response to colorectal distension was measured by luminiscence.Rats with acute TNBS-colitis displayed significant visceral hypersensitivity that was dose-dependently, but not fully, reversed by A-317491. Hypersenstivity was accompanied by an increased colonic release of ATP. Post-colitis rats also displayed visceral hypersensitivity that was dose-dependently reduced and fully normalized by A-317491 without increased release of ATP. A-317491 did not modify visceral sensitivity in controls. P2X3 mRNA and protein expression in the colon and dorsal root ganglia were similar in control, acute colitis and post-colitis groups, while colonic mRNA expression of cdk5, csk and CASK was increased in the post-colitis group only.These findings indicate that P2X3 receptors are not involved in sensory signaling under physiological conditions whereas they modulate visceral hypersensitivity during acute TNBS-colitis and even more so in the post

  12. The effect of progesterone in the prevention of the chemically induced experimental colitis in rats Efeito da progesterona na prevenção de colite experimental induzida quimicamente em ratos

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    Oguzhan Karatepe; Merih Altiok; Muharrem Battal; Gulcin Kamali; Ahu Kemik; Timucin Aydin; Servet Karahan

    2012-01-01

    PURPOSE: To study the effects of progesterone on an experimental colitis model. METHODS: Wistar albino rats were treated subcutaneously with 2mg/kg once a day during seven days Colitis was induced by intrarectal administration of 5mg trinitrobenzene sulfonic acid (TNBS). Disease activities, macroscopic and microscopic scores were evaluated. To determine the response provoked by progesterone we measured Colonic malondialdehyde (MDA), TNF alfa, IL-6 and Nitric oxide (NO) levels in addition to t...

  13. Angelica acutiloba Kitagawa Extract Attenuates DSS-Induced Murine Colitis.

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    Jang, Jong-Chan; Lee, Kang Min; Ko, Seong-Gyu

    2016-01-01

    We examined the protective effects of Angelica acutiloba Kitagawa (AAK) extract on a murine model of acute experimental colitis. Colitis was induced by 4% dextran sulfate sodium (DSS) in the drinking water of male C57BL/6 mice, for 7 consecutive days. Oral administration of AAK extract (500 mg/kg/day) significantly alleviated DSS-induced symptoms such as anorexia, weight loss, events of diarrhea or bloody stools, and colon shortening. Histological damage was also ameliorated, as evidenced by the architectural preservation and suppression of inflammatory cell infiltration in colonic samples. Treatment improved the colonic mRNA expression of different inflammatory markers: cytokines, inducible enzymes, matrix metalloproteinases, and tight junction-related proteins. In the isolated serum, IgE levels were downregulated. Collectively, these findings indicate the therapeutic potentials of AAK as an effective complementary or alternative modality for the treatment of ulcerative colitis.

  14. Differential effects of energy balance on experimentally-induced colitis

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    Sarah J McCaskey; Elizabeth A Rondini; Ingeborg M Langohr; Jenifer I Fenton

    2012-01-01

    AIM:To characterize the influence of diet-induced changes in body fat on colitis severity in SMAD3-/-mice.METHODS:SMAD3-/-mice (6-8 wk of age) were randomly assigned to receive a calorie restricted (30%of control; CR),control (CON),or high fat (HF) diet for 20 wk and were gavaged with sterile broth or with Helicobacter hepaticus (H.hepaticus) to induce colitis.Four weeks after infection,mice were sacrificed and the cecum and colons were processed for histological evaluation.RESULTS:Dietary treatment significantly influenced body composition prior to infection (P < 0.05),with CR mice having less (14% ± 2%) and HF-fed mice more body fat (32% ± 7%) compared to controls (22% ±4%).Differences in body composition were associated with alterations in plasma levels of leptin (HF > CON > CR) and adiponectin (CON > HF ≥ CR) (P < 0.05).There were no significant differences in colitis scores between CON and HF-fed mice 4 wk post-infection.Consistent with this,differences in proliferation and inflammation markers (COX-2,iNOS),and infiltrating cell types (CD3+ T lymphocytes,macrophages) were not observed.Unexpectedly,only 40% of CR mice survived infection with H.hepaticus,with mortality observed as early as 1 wk following induction of colitis.CONCLUSION:Increased adiposity does not influence colitis severity in SMAD3-/-mice.Importantly,caloric restriction negatively impacts survival following pathogen challenge,potentially due to an impaired immune response.

  15. Inflammatory cells′ role in acetic acid-induced colitis

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    Mohammad H Sanei

    2014-01-01

    Full Text Available Background: Free radicals are the known mechanisms responsible for inducing colitis with two origins: Inflammatory cells and tissues. Only the inflammatory cells can be controlled by corticosteroids. Our aim was to assess the importance of neutrophils as one of the inflammatory cells in inducing colitis and to evaluate the efficacy of corticosteroids in the treatment of inflammatory bowel disease (IBD. Materials and Methods: Thirty-six mice were divided into six groups of six mice each. Colitis was induced in three groups by exposing them to acetic acid through enema (group 1, ex vivo (group 3, and enema after immune suppression (group 5. Each group had one control group that was exposed to water injection instead of acetic acid. Tissue samples were evaluated and compared based on macroscopic damages and biochemical and pathological results. Results: Considering neutrophilic infiltration, there were significant differences between groups 1, 3, 5, and the control of group 1. Groups 3, 5, and their controls, and group 1 and the control of group 3 had significant differences in terms of goblet depletion. Based on tissue originated H 2 O 2 , we found significant differences between group 1 and its control and group 3, and also between groups 5 and the control of group 3. All the three groups were significantly different from their controls based on Ferric Reducing Ability of Plasma (FRAP and such differences were also seen between group 1 with two other groups. Conclusion: Neutrophils may not be the only cause of oxidation process in colitis, and also makes the effectiveness of corticosteroids in the treatment of this disease doubtful.

  16. Processed coffee alleviates DSS-induced colitis in mice

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    Bernd L. Fiebich

    2013-05-01

    Full Text Available ABSTRACTBackground: Coffee is one of the most widely consumed beverages in the world and it has been demonstrated that it has important therapeutic activities not only because of its caffeine content but also owing to the presence of other biologically active small molecules such as chlorogenic acid, trigonelline and cyclopentadiones. However, chlorogenic acid is degraded into catechol, pyrogallol and hydroxyhydroquinone, which are thought to induce irritation of the gastric mucosa. To reduce the content of irritant compounds processing methods have been developed prior to roasting the coffee beans.Objectives: The aim of this study was to study the anti-inflammatory and gastro-protective effects of processed coffee (Idee-Kaffee on in LPS-treated human primary monocytes and in a murine model of colon inflammation (IBD model.Results: In this study we have analyzed the effects on inflammatory events in cultured cells and in mice drinking a commercially available processed coffee. The processed coffee inhibited lipopolysaccharide (LPS-induced proinflammatory cytokines such as interleukin (IL-1, tumor necrosis factor (TNF, IL-6 and IL-8, and other inflammatory mediators such as prostaglandin (PGE2 and 8-isoprostane in cultured human primary monocytes. Oral administration of dissolved processed coffee, i.e., in its usual beverage form, improved greatly the adverse macroscopic and histological features of dextran sodium sulfate (DSS-induced colitis in mice in a dose-dependent manner. Processed coffee not only largely prevented DSS-induced colitis but also dramatically suppressed in vivo NF-B and STAT3 activities through inhibition of IB and STAT3 phosphorylation. Furthermore, this solubleFunctional Foods in Health and Disease 2013; 3(5:133-145coffee bean extract reduced the expression of proinflammatory cytokines TNF, IL-11, and IL-6 and the expression of cyclooxygenase (COX-2 in colonic tissues.Conclusions: This work identified

  17. CXCR2 knockout mice are protected against DSS-colitis-induced acute kidney injury and inflammation.

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    Ranganathan, Punithavathi; Jayakumar, Calpurnia; Manicassamy, Santhakumar; Ramesh, Ganesan

    2013-11-15

    Organ cross talk exists in many diseases of the human and animal models of human diseases. A recent study demonstrated that inflammatory mediators can cause acute kidney injury and neutrophil infiltration in a mouse model of dextran sodium sulfate (DSS)-colitis. However, the chemokines and their receptors that may mediate distant organ effects in colitis are unknown. We hypothesized that keratinocyte chemoattractant (KC)/IL-8 receptor chemokine (C-X-C motif) ligand 2 (CXCL2) mediates DSS-colitis-induced acute kidney injury. Consistent with our hypothesis, wild-type (WT) mice developed severe colitis with DSS treatment, which was associated with inflammatory cytokine and chemokine expression and neutrophil infiltration in the colon. DSS-colitis in WT was accompanied by acute kidney injury and enhanced expression of inflammatory cytokines in the kidney. However, CXCR2 knockout mice were protected against DSS-colitis as well as acute kidney injury. Moreover, the expression of cytokines and chemokines and neutrophil infiltration was blunted in CXCR2 knockout mice in the colon and kidney. Administration of recombinant KC exacerbated DSS-colitis-induced acute kidney injury. Our results suggest that KC/IL-8 and its receptor CXCR2 are critical and major mediators of organ cross talk in DSS colitis and neutralization of CXCR2 will help to reduce the incidence of acute kidney injury due to ulcerative colitis and Crohn's disease in humans.

  18. Safety and efficacy of Profermin(R) to induce remission in ulcerative colitis

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    Krag, Aleksander; Israelsen, Hans; von Ryberg, Bjørn;

    2012-01-01

    AIM: To test the efficacy and safety of Profermin(R) in inducing remission in patients with active ulcerative colitis (UC). METHODS: The study included 39 patients with mild to moderate UC defined as a Simple Clinical Colitis Activity Index (SCCAI) > 4 and < 12 (median: 7.5), who were treated ope...

  19. Light-emitting diodes at 940nm attenuate colitis-induced inflammatory process in mice.

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    Belém, Mônica O; de Andrade, Giovana M M; Carlos, Thalita M; Guazelli, Carla F S; Fattori, Victor; Toginho Filho, Dari O; Dias, Ivan F L; Verri, Waldiceu A; Araújo, Eduardo J A

    2016-09-01

    Inflammatory bowel disease (IBD) presents intense inflammatory infiltrate, crypt abscesses, ulceration and even loss of function. Despite the clinical relevance of IBD, its current therapy remains poorly effective. Infrared wavelength phototherapy shows therapeutic potential on inflammation. Our goal was to evaluate whether light-emitting diodes (LED) at 940nm are capable of mitigating the colitis-induced inflammatory process in mice. Forty male Swiss mice were assigned into five groups: control; control treated with LED therapy; colitis without treatment; colitis treated with LED therapy; colitis treated with Prednisolone. Experimental colitis was induced by acetic acid 7.5% (pH2.5) rectal administration. LED therapy was performed with light characterized by wavelength of 940nm, 45nm bandwidth, intensity of 4.05J/cm(2), total power of 270mW and total dose of 64.8J for 4min in a single application. Colitis-induced intestinal transit delay was inhibited by LED therapy. Colitis caused an increase of colon dimensions (length, diameter, total area) and colon weight (edema), which were inhibited by LED therapy. LED therapy also decreased colitis-induced tissue gross lesion, myeloperoxidase activity, microscopic tissue damage score and the presence of inflammatory infiltrate in all intestinal layers. Furthermore, LED therapy inhibited colitis-induced IL-1β, TNF-α, and IL-6 production. We conclude LED therapy at 940nm inhibited experimental colitis-induced colon inflammation in mice, therefore, rendering it a promising therapeutic approach that deserves further investigation. PMID:27424097

  20. Obestatin Accelerates the Healing of Acetic Acid-Induced Colitis in Rats

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    Aleksandra Matuszyk

    2016-01-01

    Full Text Available Obestatin, a 23-amino acid peptide derived from the proghrelin, has been shown to exhibit some protective and therapeutic effects in the gut. The aim of present study was to determine the effect of obestatin administration on the course of acetic acid-induced colitis in rats. Materials and Methods. Studies have been performed on male Wistar rats. Colitis was induced by a rectal enema with 3.5% acetic acid solution. Obestatin was administered intraperitoneally twice a day at a dose of 8 nmol/kg, starting 24 h after the induction of colitis. Seven or 14 days after the induction of colitis, the healing rate of the colon was evaluated. Results. Treatment with obestatin after induction of colitis accelerated the healing of colonic wall damage and this effect was associated with a decrease in the colitis-evoked increase in mucosal activity of myeloperoxidase and content of interleukin-1β. Moreover, obestatin administration significantly reversed the colitis-evoked decrease in mucosal blood flow and DNA synthesis. Conclusion. Administration of exogenous obestatin exhibits therapeutic effects in the course of acetic acid-induced colitis and this effect is related, at least in part, to the obestatin-evoked anti-inflammatory effect, an improvement of local blood flow, and an increase in cell proliferation in colonic mucosa.

  1. Obestatin Accelerates the Healing of Acetic Acid-Induced Colitis in Rats.

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    Matuszyk, Aleksandra; Ceranowicz, Piotr; Warzecha, Zygmunt; Cieszkowski, Jakub; Bonior, Joanna; Jaworek, Jolanta; Kuśnierz-Cabala, Beata; Konturek, Peter; Ambroży, Tadeusz; Dembiński, Artur

    2016-01-01

    Obestatin, a 23-amino acid peptide derived from the proghrelin, has been shown to exhibit some protective and therapeutic effects in the gut. The aim of present study was to determine the effect of obestatin administration on the course of acetic acid-induced colitis in rats. Materials and Methods. Studies have been performed on male Wistar rats. Colitis was induced by a rectal enema with 3.5% acetic acid solution. Obestatin was administered intraperitoneally twice a day at a dose of 8 nmol/kg, starting 24 h after the induction of colitis. Seven or 14 days after the induction of colitis, the healing rate of the colon was evaluated. Results. Treatment with obestatin after induction of colitis accelerated the healing of colonic wall damage and this effect was associated with a decrease in the colitis-evoked increase in mucosal activity of myeloperoxidase and content of interleukin-1β. Moreover, obestatin administration significantly reversed the colitis-evoked decrease in mucosal blood flow and DNA synthesis. Conclusion. Administration of exogenous obestatin exhibits therapeutic effects in the course of acetic acid-induced colitis and this effect is related, at least in part, to the obestatin-evoked anti-inflammatory effect, an improvement of local blood flow, and an increase in cell proliferation in colonic mucosa.

  2. Anti-Inflammatory Effects of Inonotus obliquus in Colitis Induced by Dextran Sodium Sulfate

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    Se Young Choi; Sun Jin Hur; Chi Sun An; Yun Hui Jeon; Young Jun Jeoung; Jong Phil Bak; Beong Ou Lim

    2010-01-01

    A total of 28 male BALB/c mice (average weight 20.7 ± 1.6 g) were divided into 4 treatment groups and fed a commercial diet (A), a commercial diet + induced colitis by dextran sodium sulfate (DSS) (B), Inonotus obliquus (IO) administration (C), and IO administration + induced colitis by DSS (D). IO treatment (C, D) decreased the expression of tumor necrosis factor (TNF)-α and signal transducers and activators of transcription (STAT)1 compared to those of the colitis induced group (B). The exp...

  3. Exogenous Ghrelin Accelerates the Healing of Acetic Acid-Induced Colitis in Rats.

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    Matuszyk, Aleksandra; Ceranowicz, Piotr; Warzecha, Zygmunt; Cieszkowski, Jakub; Ceranowicz, Dagmara; Gałązka, Krystyna; Bonior, Joanna; Jaworek, Jolanta; Bartuś, Krzysztof; Gil, Krzysztof; Olszanecki, Rafał; Dembiński, Artur

    2016-01-01

    Previous studies have shown that ghrelin reduces colonic inflammation induced by trinitrobenzene sulfonic acid and dextran sodium sulfate. In the present study we determined the effect of treatment with ghrelin on the course of acetic acid-induced colitis in rats. Rectal administration of 3% acetic acid solution led to induction of colitis in all animals. Damage of the colonic wall was accompanied by an increase in mucosal concentration of pro-inflammatory interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), as well mucosal activity of myeloperoxidase. Moreover, induction of colitis led to a reduction in colonic blood flow and DNA synthesis. Administration of ghrelin after induction of colitis led to faster regeneration of the colonic wall and reduction in colonic levels of IL-1β, TNF-α, and myeloperoxidase. In addition, treatment with ghrelin improved mucosal DNA synthesis and blood flow. Our study disclosed that ghrelin exhibits a strong anti-inflammatory and healing effect in acetic acid-induced colitis. Our current observation in association with previous findings that ghrelin exhibits curative effect in trinitrobenzene sulfonic acid- and dextran sodium sulfate-induced colitis suggest that therapeutic effect of ghrelin in the colon is universal and independent of the primary cause of colitis. PMID:27598133

  4. The effect of progesterone in the prevention of the chemically induced experimental colitis in rats Efeito da progesterona na prevenção de colite experimental induzida quimicamente em ratos

    Directory of Open Access Journals (Sweden)

    Oguzhan Karatepe

    2012-01-01

    Full Text Available PURPOSE: To study the effects of progesterone on an experimental colitis model. METHODS: Wistar albino rats were treated subcutaneously with 2mg/kg once a day during seven days Colitis was induced by intrarectal administration of 5mg trinitrobenzene sulfonic acid (TNBS. Disease activities, macroscopic and microscopic scores were evaluated. To determine the response provoked by progesterone we measured Colonic malondialdehyde (MDA, TNF alfa, IL-6 and Nitric oxide (NO levels in addition to the MPO (Myeloperoxidase and caspase-3 activities. RESULTS: Progesterone ameliorated significantly the macroscopic and microscopic scores. TNBS-induced colitis significantly increased the colonic MDA levels and caspase-3 activities in group 2 in comparison to the control group. The results of the study revealed a decline in MDA, NO, IL6 and TNF-α levels in the colon tissue and in blood due to progesterone therapy in group 3 when compared to the group 2, a significant improvement. Progesterone treatment was associated with decreased MDA, MPO, TNF alfa and caspase-3 activity. CONCLUSION: Progesterone therapy decreased oxidative damage in the colonic mucosa.OBJETIVO: Investigar os efeitos da progesterona em um modelo de colite experimental. MÉTODOS: Ratos albinos Wistar foram tratados subcutaneamente com 2mg/kg por dia durante sete dias. A colite foi induzida por administração intrarretal de 5mg ácido sulfônico trinitrobenzeno (TNBS. Foram avaliadas as atividades da doença, escores macroscópicos e microscópicos Para determinar a resposta provocada pela progesterona foi medida no cólon os níveis de malondialdeído (MDA, TNF alfa, IL-6 e óxido nítrico (NO, além da atividade da MPO (Myeloperoxidase e caspase-3. RESULTADOS: A progesterone melhorou significantemente os escores macroscópicos e microscópicos. A colite induzida pelo TNBS significantemente aumentou os níveis colônicos de MDA e a atividade da caspase-3 no grupo 2 em comparação com o grupo

  5. Relationship between Mast Cells and the Colitis with Relapse Induced by Trinitrobenzesulphonic Acid in Wistar Rats

    Directory of Open Access Journals (Sweden)

    Ana Carolina Luchini

    2009-01-01

    Full Text Available The present study aimed to clarify the role of mast cells in colitis with relapse induced in Wistar rats by trinitrobenzenosulphonic acid. Colitis induction increased the histamine concentration in the colon, which peaked on day 26. The number of mast cells, probably immature, was ten times higher on day 8. Different from animals infected with intestinal parasites, after colitis remission, mast cells do not migrate to the spleen, showing that mast cell proliferation presents different characteristics depending on the inflammation stimuli. Treatment with sulfasalazine, doxantrazole, quercetin, or nedocromil did not increase the histamine concentration or the mast cell number in the colon on day 26, thereby showing absence of degranulation of these cells. In conclusion, although mast cell proliferation is associated with colitis, these cells and their mediators appear to play no clear role in the colitis with relapses.

  6. Involvement of lymphocytes in dextran sulfate sodium-induced experimental colitis

    Institute of Scientific and Technical Information of China (English)

    Tae Woon Kim; Jae Nam Seo; Young Ho Suh; Hyo Jin Park; Ju Hyun Kim; Ji Young Kim; Kwon Tk Oh

    2006-01-01

    AIM: To investigate the roles of lymphocytes in the development of dextran sulfate sodium-induced colitis.METHODS: Using various doses of dextran sulfate sodium (DSS), we induced colitis in wild-type B6control and Rag-1 knockout (H-2b haplotype) mice,and evaluated the colitis in terms of symptomatic and histologic parameters, such as weight loss, survival,severity of diarrhea, shortage of colon length and histological changes. Symptomatic parameters were checked daily and histological changes were scored.RESULTS: Although development of colitis in Rag-1knockout mice treated with high dose (5%) of DSS was comparable to that in B6 control mice, colitis progression was much more tolerable in Rag-1 knockout mice compared to than in B6 mice treated with low dose (1.5%)DSS. Symptomatic parameters as well as histopathologic changes were improved in Rag-1 knockout mice.CONCLUSION: These results indicate that the presence of lymphocytes contributes to colitis progression at low dose of DSS stimulation. Lymphocytes may play roles as an aggravating factor in DSS-induced colitis.

  7. Hypoxia-inducible factor 1 alpha and vascular endothelial growth factor overexpression in ischemic colitis

    Institute of Scientific and Technical Information of China (English)

    Tomoyuki Okuda; Takeshi Azuma; Masahiro Ohtani; Ryuho Masaki; Yoshiyuki Ito; Yukinao Yamazaki; Shigeji Ito; Masaru Kuriyama

    2005-01-01

    AIM: To examine the etiology and pathophysiology in human ischemic colitis from the viewpoint of ischemic favors such as hypoxia-inducible factor 1 alpha (HIF-1alpha and vascular endothelial growth factor (VEGF).METHODS: Thirteen patients with ischemic colitis and 21 normal controls underwent colonoscopy. The follow-up colonoscopy was performed in 8 patients at 7 to 10 d after theoccurrence of ischemic colitis. Biopsy samples were subjected to real-time RT-PCR and immunohistochemistry to detect the expression of HIF-1 alpha and VEGF.RESULTS: HIF-1 alpha and VEGF expression were found in the normal colon tissues by RT-PCR and immunohistochemistry.HIF-1 alpha and VEGF were overexpressed in the lesions of ischemic colitis. Overexpressed HIF-1 alpha and VEGF RNA quickly decreased to the normal level in the scar regions at 7 to 10 d after the occurrence of ischemic colitis.CONCLUSION: Constant expression of HIF-1 alpha and VEGF in normal human colon tissue suggested that HIF-1alpha and VEGF play an important role in maintaining tissue integrity. We confirmed the ischemic crisis in ischemic colitis at the molecular level, demonstrating overexpression of HIF-1 alpha and VEGF in ischemic lesions. These ischemic factors may play an important role in the pathophysiology of ischemic colitis.

  8. Therapeutic treatment with a novel hypoxia-inducible factor hydroxylase inhibitor (TRC160334 ameliorates murine colitis

    Directory of Open Access Journals (Sweden)

    Gupta R

    2014-01-01

    Full Text Available Ram Gupta,1 Anita R Chaudhary,2 Binita N Shah,1 Avinash V Jadhav,3 Shitalkumar P Zambad,1 Ramesh Chandra Gupta,4 Shailesh Deshpande,4 Vijay Chauthaiwale,4 Chaitanya Dutt4 1Department of Pharmacology, 2Cellular and Molecular Biology, 3Preclinical Safety Evaluation, 4Discovery, Torrent Research Centre, Torrent Pharmaceuticals Ltd, Gandhinagar, Gujarat, India Background and aim: Mucosal healing in inflammatory bowel disease (IBD can be achieved by improvement of intestinal barrier protection. Activation of hypoxia-inducible factor (HIF has been identified as a critical factor for barrier protection during mucosal insult and is linked with improvement in symptoms of colitis. Although prophylactic efficacy of HIF hydroxylase inhibitors in murine colitis have been established, its therapeutic efficacy in clinically relevant therapeutic settings have not been established. In the present study we aim to establish therapeutic efficacy of TRC160334, a novel HIF hydroxylase inhibitor, in animal models of colitis. Methods: The efficacy of TRC160334 was evaluated in two different mouse models of colitis by oral route. A prophylactic efficacy study was performed in a 2,4,6-trinitrobenzene sulfonic acid-induced mouse model of colitis representing human Crohn's disease pathology. Additionally, a therapeutic efficacy study was performed in a dextran sulfate sodium-induced mouse model of colitis, a model simulating human ulcerative colitis. Results: TRC160334 treatment resulted in significant improvement in disease end points in both models of colitis. TRC160334 treatment resulted into cytoprotective heatshock protein 70 induction in inflamed colon. TRC160334 successfully attenuated the rate of fall in body weight, disease activity index, and macroscopic and microscopic scores of colonic damage leading to overall improvement in study outcome. Conclusion: Our findings are the first to demonstrate that therapeutic intervention with a HIF hydroxylase inhibitor

  9. Effects of orally administered bovine lactoperoxidase on dextran sulfate sodium-induced colitis in mice.

    Science.gov (United States)

    Shin, Kouichirou; Horigome, Ayako; Yamauchi, Koji; Takase, Mitsunori; Yaeshima, Tomoko; Iwatsuki, Keiji

    2008-07-01

    The effect of lactoperoxidase (LPO) on dextran sulfate sodium-induced colitis was examined in mice. After 9 d of colitis induction, weight loss, colon shortening, and the histological score were significantly suppressed in mice orally administered LPO (62.5 mg/body/d) as compared to a group administered bovine serum albumin. These results suggest that LPO exhibits anti-inflammatory effects in the gastrointestinal tract.

  10. Effect of ethanolic extract of leaves of Paederia foetida Linn. on acetic acid induced colitis in albino rats

    Directory of Open Access Journals (Sweden)

    Swarnamoni Das

    2013-01-01

    Conclusions: The ethanolic extract of leaves of P. foetida showed significant amelioration of experimentally induced colitis, which may be attributed to its anti-inflammatory and antioxidant property.

  11. Reactive arthritis induced by recurrent Clostridium difficile colitis

    Directory of Open Access Journals (Sweden)

    Allison Marr

    2012-01-01

    Full Text Available Clostridium difficile colitis is a common infection that can be difficult to resolve and may result in recurrent infections. Reactive arthritis is a rare presentation of this disease and its treatment is not well differentiated in the literature. We describe a case of reactive arthritis occurring in a patient with a history of recurrent Clostridium difficile colitis while currently receiving a taper of oral vancomycin. His arthritis symptoms resolved with corticosteroids and continued treatment with anticlostridial antibiotics.

  12. Intestinal microbiome analyses identify melanoma patients at risk for checkpoint-blockade-induced colitis.

    Science.gov (United States)

    Dubin, Krista; Callahan, Margaret K; Ren, Boyu; Khanin, Raya; Viale, Agnes; Ling, Lilan; No, Daniel; Gobourne, Asia; Littmann, Eric; Huttenhower, Curtis; Pamer, Eric G; Wolchok, Jedd D

    2016-01-01

    The composition of the intestinal microbiota influences the development of inflammatory disorders. However, associating inflammatory diseases with specific microbial members of the microbiota is challenging, because clinically detectable inflammation and its treatment can alter the microbiota's composition. Immunologic checkpoint blockade with ipilimumab, a monoclonal antibody that blocks cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) signalling, is associated with new-onset, immune-mediated colitis. Here we conduct a prospective study of patients with metastatic melanoma undergoing ipilimumab treatment and correlate the pre-inflammation faecal microbiota and microbiome composition with subsequent colitis development. We demonstrate that increased representation of bacteria belonging to the Bacteroidetes phylum is correlated with resistance to the development of checkpoint-blockade-induced colitis. Furthermore, a paucity of genetic pathways involved in polyamine transport and B vitamin biosynthesis is associated with an increased risk of colitis. Identification of these biomarkers may enable interventions to reduce the risk of inflammatory complications following cancer immunotherapy. PMID:26837003

  13. Exosomes released by granulocytic myeloid-derived suppressor cells attenuate DSS-induced colitis in mice.

    Science.gov (United States)

    Wang, Yungang; Tian, Jie; Tang, Xinyi; Rui, Ke; Tian, Xinyu; Ma, Jie; Ma, Bin; Xu, Huaxi; Lu, Liwei; Wang, Shengjun

    2016-03-29

    Myeloid-derived suppressor cells (MDSC) have been described in inflammatory bowel disease (IBD), but their role in the disease remains controversial. We sought to define the effect of granulocytic MDSC-derived exosomes (G-MDSC exo) in dextran sulphate sodium (DSS)-induced murine colitis. G-MDSC exo-treated mice showed greater resistance to colitis, as reflected by lower disease activity index, decreased inflammatory cell infiltration damage. There was a decrease in the proportion of Th1 cells and an increase in the proportion of regulatory T cells (Tregs) in mesenteric lymph nodes (MLNs) from G-MDSC exo-treated colitis mice. Moreover, lower serum levels of interferon (IFN)-γ and tumor necrosis factor (TNF)-α were detected in G-MDSC exo-treated colitis mice. Interestingly, inhibition of arginase (Arg)-1 activity in G-MDSC exo partially abrogated the spontaneous improvement of colitis. In addition, G-MDSC exo could suppress CD4+ T cell proliferation and IFN-γ secretion in vitro and inhibit the delayed-type hypersensitivity (DTH) response, and these abilities were associated with Arg-1 activity. Moreover, G-MDSC exo promoted the expansion of Tregs in vitro. Taken together, these results suggest that G-MDSC exo attenuate DSS-induced colitis through inhibiting Th1 cells proliferation and promoting Tregs expansion.

  14. Topical application of glycyrrhizin preparation ameliorates experimentally induced colitis in rats

    Institute of Scientific and Technical Information of China (English)

    Tomohiro Kudo; Shinichi Okamura; Yajing Zhang; Takashige Masuo; Masatomo Mori

    2011-01-01

    AIM: To examine the efficacy of glycyrrhizin preparation (GL-p) in the treatment of a rat model of ulcerative colitis (UC). METHODS: Experimental colitis was induced by oral administration of dextran sodium sulfate. Rats with colitis were intrarectally administered GL-p or saline. The extent of colitis was evaluated based on body weight gain,colon wet weight,and macroscopic damage score. The expression levels of pro-inflammatory cytokines and chemokines in the inflamed mucosa were measured by cytokine antibody array analysis. The effect of GL-p on myeloperoxidase (MPO) activity in the inflamed mucosa and purified enzyme was assayed. RESULTS: GL-p treatment significantly ameliorated the extent of colitis compared to sham treatment with saline. Cytokine antibody array analysis showed that GL-p treatment significantly decreased the expression levels of pro-inflammatory cytokines and chemokines,including interleukin (IL)-1β,IL-6,tumor necrosis factor-α,cytokine-induced neutrophil chemoattractant-2,and monocyte chemoattractant protein-1 in the inflamed mucosa. Furthermore,GL-p inhibited the oxidative activity of mucosal and purified MPO. CONCLUSION: GL-p enema has a therapeutic effect on experimental colitis in rats and may be useful in the treatment of UC.

  15. [Meloxicam-induced colitis revealed by acute abdominal pain].

    Science.gov (United States)

    Seddik, H; Rabhi, M

    2013-03-01

    Whether intestinal toxicity of preferential or selective COX-2 inhibitors is reduced compared with that of standard NSAIDs is controversial. A 26-year-old woman presented with acute abdominal pain and bloody diarrhoea a few days after beginning meloxicam treatment. Endoscopic examination of the colon showed erythematous and ulcerative lesions involving 15 cm of the left colon. No aetiology has been found for colitis. Diarrhea disappeared 1 week after meloxicam was stopped. Total colonoscopy 3 months and 2 years later was normal. The role of meloxicam in the etiology of colitis was considered plausible. This report and a few other cases in the literature suggest that cyclooxygenase-2 selective non-steroidal anti-inflammatory drug inhibitor toxicity should be investigated in case of unexplained acute colitis. PMID:23537413

  16. Ginseng Berry Extract Attenuates Dextran Sodium Sulfate-Induced Acute and Chronic Colitis

    Directory of Open Access Journals (Sweden)

    Wei Zhang

    2016-04-01

    Full Text Available This study investigates the in vivo functions of ginseng berry extract (GB as a therapy for dextran sodium sulfate (DSS-induced colitis. C57BL/6 mice were given drinking water containing DSS (3% for eight days to induce acute colitis. At the same time, the mice received an oral dose of GB (50 mg/kg once daily. The GB-treated mice were less susceptible to the development of acute colitis than were control mice treated with saline, as determined by weight loss, disease activity, and colon histology. The administration of GB to DSS-treated mice also reduced the numbers and inhibited the activation of colon-infiltrating T cells, neutrophils, intestinal CD103−CD11c+ dendritic cells (cDCs, and macrophages. In addition, GB treatment promoted the migration of CD103+CD11c+ cDCs and expansion of Foxp3+ regulatory T cells in the colons of DSS-treated mice. Similarly, in the DSS-induced chronic colitis model, GB treatment improved the macroscopic and histological appearance of the colon wall when compared to untreated control mice, as indicated by longer colon length and lower histological scores. This is the first report to show that oral administration of GB suppresses immune activation and protects against experimentally induced colitis.

  17. Effects of ulinastatin in experimental colitis induced by dextran sulfate sodium in rats

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    AIM: Ulinastatin has been reported to be beneficial for maintenance of steroid-refractory inflammatory bowel disease (IBD), but the mechanism underlying remains uncertain. Leukocyte recruitment to inflammatory site plays an important role in the pathogenesis of IBD, analysis of leukocyte and endothelium interaction may provide new avenues for treatment of IBD. In this study, we evaluated the efficacy of Ulinastatin in dextran sulfate sodium (DSS) induced colitis rat model using intravital video microscopy. METHODS: Rats were given drinking water containing 3.5% (W/V) DSS for 10 days then 1% for 14 days. DSS induced colitis rats were treated Ulinastatin 3 000 unit*kg-1*d-1 via intraperitoneum during 1% DSS feeding. Controls received distilled water for 24 days. Body weight was determined for all groups. Colitis severity was assessed using histological scoring systems by H&E sections. Intravital microscopic techniques were used to quantitate leukocyte adhesion (LA), leukocyte emigration (LE) and venular protein leakage (VPL) in rat mesentery. RESULTS: DSS induced loss of body weight, whereas Ulinastatin-treated rat showed a significant increase in body weight. Histological analysis revealed improvement of colitis such as leukocyte infiltration, loss of goblet cells, transmural edema. DSS intake elicited increase in LA, LE, and VPL compared to control group. Ulinstatin significantly reversed the increase in LA, LE, and VPL induced by DSS. CONCLUSION: Administration of Ulinastatin effectively ameliorates experimental colitis by interfering with leukocyte recruitment, and may become a potential candidate for control of inflammation of IBD.

  18. Pseudomembranous colitis

    Science.gov (United States)

    Antibiotic-associated colitis; Colitis - pseudomembranous; Necrotizing colitis; C difficile - pseudomembranous ... this bacteria from 1 person to another. Pseudomembranous colitis is uncommon in children, and rare in infants. ...

  19. Myristica fragrans seed extract protects against dextran sulfate sodium-induced colitis in mice.

    Science.gov (United States)

    Kim, Hyojung; Bu, Youngmin; Lee, Beom-Joon; Bae, Jinhyun; Park, Sujin; Kim, Jinsung; Lee, Kyungjin; Cha, Jae-Myung; Ryu, Bongha; Ko, Seok-Jae; Han, Gajin; Min, Byungil; Park, Jae-Woo

    2013-10-01

    Nutmeg (seed of Myristica fragrans [MF]) is one of the most commonly used spices in the world and also a well-known herb for the treatment of various intestinal diseases, including colitis in traditional Korean medicine. The purpose of the current study was to investigate whether water extract of MF (MFE) can protect against dextran sulfate sodium (DSS) induced colitis in a mouse model. Colitis was induced by 5% DSS in balb/c mice. MFE (100, 300 or 1000 mg/kg) was orally administered to the mice twice a day for 7 days. Body weight, colon length, clinical score, and histological score were assessed to determine the effects on colitis. Proinflammatory cytokines (interferon-γ, tumor necrosis factor-α, interleukin [IL]-1β, and IL-6) were measured to investigate the mechanisms of action. MFE dose dependently inhibited the colon shortening and histological damage to the colon. However, it did not prevent weight loss. MFE also inhibited proinflammatory cytokines. The current results suggest that MFE ameliorates DSS-induced colitis in mice by inhibiting inflammatory cytokines. Further investigation, including the exact mechanisms is needed.

  20. REGULATION OF INDUCIBLE NITRIC OXIDE SYNTHASE IN COLLAGENOUS COLITIS

    DEFF Research Database (Denmark)

    Andresen, Lars

    2004-01-01

    ulcerøs colitis, der er karakteriseret ved en kronisk recidiverende, sårdannende inflammation af kolorektalslimhinden. I nærværende sammenlignende studie er ekspressionen af iNOS og aktiviteten af enzymets transkriptionsfaktor, nukleær faktor-kappa B (NF-B), i slimhindebiopsier fra colonslimhinden hos...

  1. Dextran Sulfate Sodium (DSS)-Induced Acute Colitis in the Rat.

    Science.gov (United States)

    Martin, Jérôme C; Bériou, Gaëlle; Josien, Régis

    2016-01-01

    Inflammatory bowel diseases (IBDs) are complex multifactorial disease thought to result from inappropriate immune responses to the gut microbiota, in genetically susceptible individuals, under the influence of environmental factors. Among the different animal models developed to help in understanding IBDs pathophysiological mechanisms as well as to achieve pharmacological preclinical studies, the dextran sulfate sodium (DSS)-induced colitis model is the most widely used because of its simplicity, cost-effectiveness, and similarity with human IBDs. This section provides with a detailed protocol that we validated in our laboratory to perform DSS-induced acute colitis in the Sprague-Dawley (SPD) rat.

  2. Increased Production of Lysozyme Associated with Bacterial Proliferation in Barrett's Esophagitis, Chronic Gastritis, Gluten-induced Atrophic Duodenitis (Celiac Disease), Lymphocytic Colitis, Collagenous Colitis, Ulcerative Colitis and Crohn's Colitis.

    Science.gov (United States)

    Rubio, Carlos A

    2015-12-01

    The mucosa of the esophagus, the stomach, the small intestine, the large intestine and rectum are unremittingly challenged by adverse micro-environmental factors, such as ingested pathogenic and non-pathogenic bacteria, and harsh secretions with digestive properties with disparate pH, as well as bacteria and secretions from upstream GI organs. Despite the apparently inauspicious mixture of secretions and bacteria, the normal GI mucosa retains a healthy state of cell renewal. To by-pass the tough microenvironment, the epithelia of the GI react by speeding-up cell exfoliation, by increasing peristalsis, eliminating bacteria through secretion of plasma cell-immunoglobulins and by increasing production of natural antibacterial enzymes (lysozyme) and host defense peptides (defensin-5). Lysozyme was recently found up-regulated in Barrett's esophagitis, in chronic gastritis, in gluten-induced atrophic duodenitis (celiac disease), in collagenous colitis, in lymphocytic colitis and in Crohn's colitis. This up-regulation is a response directed towards the special types of bacteria thriving in the microenvironment in each of the aforementioned clinical inflammatory maladies. The purpose of that up-regulation is to protect the mucosa affected by the ongoing chronic inflammation. Bacterial antibiotic resistance continues to exhaust our supply of effective antibiotics. The future challenge is how to solve the increasing menace of bacterial resistance to anti-bacterial drugs. Further research on natural anti-bacterial enzymes such as lysozyme, appears mandatory. PMID:26637845

  3. Sodium arsenite reduces severity of dextran sulfate sodium-induced ulcerative colitis in rats

    Institute of Scientific and Technical Information of China (English)

    Joshua J. MALAGO; Hortensia NONDOLI

    2008-01-01

    The histopathological features and the associated clinical findings of ulcerative colitis (UC) are due to persistent inflammatory response in the colon mucosa. Interventions that suppress this response benefit UC patients. We tested whether sodium arsenite (SA) benefits rats with dextran sulfate sodium (DSS)-colitis. The DSS-colitis was induced by 5% DSS in drinking water. SA (10 mg/kg; intraperitoneally) was given 8 h before DSS treatment and then every 48 h for 3 cycles of 7,14 or 21 d. At the end of each cycle rats were sacrificed and colon sections processed for histological examination. DSS induced diarrhea, loose stools, hemoccult positive stools, gross bleeding, loss of body weight, loss of epithelium, crypt damage, depletion of goblet cells and infiltration of inflammatory cells. The severity of these changes increased ir the order of Cycles 1,2 and 3. Treatment of rats with SA significantly reduced this severity and improved the weight gain.

  4. Complement component 6 deficiency increases susceptibility to dextran sulfate sodium-induced murine colitis.

    Science.gov (United States)

    Ding, Peipei; Li, Ling; Huang, Tianbao; Yang, Chaoqun; Xu, Enjie; Wang, Na; Zhang, Long; Gu, Hongyu; Yao, Xudong; Zhou, Xuhui; Hu, Weiguo

    2016-11-01

    As a potent effector of innate immunity, the complement system has been shown to be involved in the pathogenesis of inflammatory bowel disease (IBD). However, the role of the membrane attack complex (MAC) in the development of IBD is still largely unknown. Here, we used C6-deficient mice in which MAC formation was blocked due to the absence of C6 to develop an acute colitis model by the administration of dextran sulfate sodium (DSS). The results showed that DSS-induced colitis was aggravated in C6-deficient mice compared with wild-type (WT) mice, as represented by the markedly greater weight loss, higher disease activity index (DAI), shortened colon length, more severe histological injury with increased epithelial ulcerations, and massively increased infiltration of leukocytes accompanied by much higher myeloperoxidase (MPO) levels in local inflammatory colonic sites. In addition, the DSS-induced colitis in C6-deficient mice could be significantly ameliorated by the exogenous C6 from WT sera. Furthermore, the significantly enhanced production of pro-inflammatory mediators, including IL-1β, IL-6, CXCL-1, CCL-3, TGF-β1 and IL-17F, was also observed in C6-deficient mice. Unexpectedly, the aggravated colitis in C6-deficient mice may be not due to the increase of lipopolysaccharide (LPS) levels in serum. Overall, we demonstrated that MAC exerts a protective role in acute colitis, strongly highlighting the host defense function of the complement system. PMID:27316715

  5. Effect of Scutellariae Radix extract on experimental dextran-sulfate sodium-induced colitis in rats

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To investigate the effect of Scutellariae Radix extract (SRE) on ulcerative colitis (UC) in rats induced by dextran-sulfate sodium (DSS).METHODS: Colitis was induced in male Sprague-Dawley (SD) rats (170-180 g) by 4% dextran sulfate sodium (DSS, wt/v; MW 54000) in drinking water for 8 d. The treated rats received 4% DSS and SRE orally (100 mg/kg per day). Control rats received either tap water or SRE only. Macroscopic assessment which included body weight changes, fecal occult blood and stool consistency were determined daily. At the appointed time, the rats were sacrificed and the entire colons were removed. The colon length and the myeloperoxidase (MPO) activity were measured. The severity of colitis was graded by morphological and histological assessments. The ion transport activity of the colonic mucosa was assessed by electrophysiological technique. RESULTS: Rats treated with oral administration of 4% DSS regularly developed clinical and macroscopic signs of colitis. Treatment with SRE relieved the symptoms, including the reduction in body weight, shortening and ulceration of the colon. Administration of SRE also significantly reduced the histological damage induced by DSS. Moreover, the Isc responses of the colonic mucosa to forskolin were suppressed after the induction of colitis. The stimulated ion transport activity of DSS-rats treated with SRE displayed significant improvement in the secretory responsiveness.CONCLUSION: SRE was effective in treating acute DSS -induced ulcerative colitis, as gauged by reduced clinical disease, improved macroscopic and histological damage scores, and enhanced recovery of normal colonic secretory function.

  6. Anti-inflammatory effects of Inonotus obliquus in colitis induced by dextran sodium sulfate.

    Science.gov (United States)

    Choi, Se Young; Hur, Sun Jin; An, Chi Sun; Jeon, Yun Hui; Jeoung, Young Jun; Bak, Jong Phil; Lim, Beong Ou

    2010-01-01

    A total of 28 male BALB/c mice (average weight 20.7 +/- 1.6 g) were divided into 4 treatment groups and fed a commercial diet (A), a commercial diet + induced colitis by dextran sodium sulfate (DSS) (B), Inonotus obliquus (IO) administration (C), and IO administration + induced colitis by DSS (D). IO treatment (C, D) decreased the expression of tumor necrosis factor (TNF)-alpha and signal transducers and activators of transcription (STAT)1 compared to those of the colitis induced group (B). The expressions of IL-4 and STAT6 were decreased in group D compared to the colitis induced group (B). The serum immunoglobulin (Ig)E level decreased in IO treatment groups (C, D) compared to no IO treatment groups (A and B) although there was no significant difference between the IO treatment groups. Extract from IO itself had a weak cytotoxic effect on murine macrophage cell line (RAW264.7 cells). Extract from IO inhibited lipopolysaccharide- (LPS-) induced, TNF-alpha, STAT1, pSTAT1, STAT6, and pSTAT6 production in RAW264.7 cells. PMID:20300439

  7. Anti-Inflammatory Effects of Inonotus obliquus in Colitis Induced by Dextran Sodium Sulfate

    Directory of Open Access Journals (Sweden)

    Se Young Choi

    2010-01-01

    Full Text Available A total of 28 male BALB/c mice (average weight 20.7 ± 1.6 g were divided into 4 treatment groups and fed a commercial diet (A, a commercial diet + induced colitis by dextran sodium sulfate (DSS (B, Inonotus obliquus (IO administration (C, and IO administration + induced colitis by DSS (D. IO treatment (C, D decreased the expression of tumor necrosis factor (TNF-α and signal transducers and activators of transcription (STAT1 compared to those of the colitis induced group (B. The expressions of IL-4 and STAT6 were decreased in group D compared to the colitis induced group (B. The serum immunoglobulin (IgE level decreased in IO treatment groups (C, D compared to no IO treatment groups (A and B although there was no significant difference between the IO treatment groups. Extract from IO itself had a weak cytotoxic effect on murine macrophage cell line (RAW264.7 cells. Extract from IO inhibited lipopolysaccharide- (LPS- induced, TNF-α, STAT1, pSTAT1, STAT6, and pSTAT6 production in RAW264.7 cells.

  8. Repeated Predictable Stress Causes Resilience against Colitis-Induced Behavioral Changes in Mice

    Directory of Open Access Journals (Sweden)

    Ahmed M Hassan

    2014-11-01

    Full Text Available Inflammatory bowel disease is associated with an increased risk of mental disorders and can be exacerbated by stress. In this study which was performed with male 10-week old C57Bl/6N mice, we used dextran sulfate sodium (DSS-induced colitis to evaluate behavioral changes caused by intestinal inflammation, to assess the interaction between repeated psychological stress (water avoidance stress, WAS and colitis in modifying behavior, and to analyze neurochemical correlates of this interaction. A 7-day treatment with DSS (2 % in drinking water decreased locomotion and enhanced anxiety-like behavior in the open field test and reduced social interaction. Repeated exposure to WAS for 7 days had little influence on behavior but prevented the DSS-induced behavioral disturbances in the open field and social interaction tests. In contrast, repeated WAS did not modify colon length, colonic myeloperoxidase content and circulating proinflammatory cytokines, parameters used to assess colitis severity. DSS-induced colitis was associated with an increase in circulating neuropeptide Y (NPY, a rise in the hypothalamic expression of cyclooxygenase-2 mRNA and a decrease in the hippocampal expression of NPY mRNA, brain-derived neurotrophic factor mRNA and mineralocorticoid receptor mRNA. Repeated WAS significantly decreased the relative expression of corticotropin-releasing factor mRNA in the hippocampus. The effect of repeated WAS to blunt the DSS-evoked behavioral disturbances was associated with a rise of circulating corticosterone and an increase in the expression of hypothalamic NPY mRNA. These results show that experimental colitis leads to a particular range of behavioral alterations which can be prevented by repeated WAS, a model of predictable chronic stress, while the severity of colitis remains unabated. We conclude that the mechanisms underlying the resilience effect of repeated WAS involves hypothalamic NPY and the hypothalamic-pituitary-adrenal axis.

  9. Balsalazine decreases intestinal mucosal permeability of dextran sulfate sodium-induced colitis in mice

    Institute of Scientific and Technical Information of China (English)

    Xiao-chang LIU; Qiao MEI; Jian-ming XU; Jing HU

    2009-01-01

    Aim:To investigate the effect of balsalazine treatment on intestinal mucosal permeability in dextran sulfate sodium (DSS)-induced colitis and to determine the mechanism of the balsalazine-induced changes.Methods:Experimental colitis was induced in C57BL/6J mice by the administration of 5% DSS.Balsalazine was administered intragastrically at doses of 42,141,and 423 mg/kg.The disease activity index (DAI) score was evaluated and colon tissue was collected for the assessment of histological changes.The amount of malondialdehyde (MDA) in the colon was determined,along with the activity of myeloperoxidase (MPO),superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px).Mucosa from the small intestine was collected to determine the levels of tumor necrosis factor (TNF)-α and interferon (IFN)-Y.The mucosa was ultrastructurally examined with transmission electron microscopy and intestinal permeability was assayed using Evans blue.Results:Balsalazine was found to reduce the DAI score and the histological index (HI) score,decrease the MDA content and the activity of MPO,and increase the activity of SOD and GSH-Px in colitis mice.At the same time,balsalazine ameliorated microvillus and tight junction structure,resulting in a decrease in the amount of Evans blue permeating into the intestinal wall and the levels of TNF-α and IFN-Y in colitis mice.Conclusion:In colitis mice,the anti-colitis effect of balsalazine results in a decrease in intestinal mucosal permeability.The mechanism of this effect is partly associated with balsalazine's antioxidative and anti-inflammatory effects.

  10. The effect of ileotransversostomy on carrageenan-induced colitis in guinea pigs

    DEFF Research Database (Denmark)

    Poulsen, Steen Seier

    1983-01-01

    By oral administration of degraded carrageenan a colitis-like disease can be induced in guinea pigs which almost exclusively affects the caecum. To study the effect of degraded carrageenan on the distal colon and rectum, an ileotransversostomy was performed. In the non-operated group of animals...

  11. The intestinal microbiota plays a role in Salmonella-induced colitis independent of pathogen colonization.

    Directory of Open Access Journals (Sweden)

    Rosana B R Ferreira

    Full Text Available The intestinal microbiota is composed of hundreds of species of bacteria, fungi and protozoa and is critical for numerous biological processes, such as nutrient acquisition, vitamin production, and colonization resistance against bacterial pathogens. We studied the role of the intestinal microbiota on host resistance to Salmonella enterica serovar Typhimurium-induced colitis. Using multiple antibiotic treatments in 129S1/SvImJ mice, we showed that disruption of the intestinal microbiota alters host susceptibility to infection. Although all antibiotic treatments caused similar increases in pathogen colonization, the development of enterocolitis was seen only when streptomycin or vancomycin was used; no significant pathology was observed with the use of metronidazole. Interestingly, metronidazole-treated and infected C57BL/6 mice developed severe pathology. We hypothesized that the intestinal microbiota confers resistance to infectious colitis without affecting the ability of S. Typhimurium to colonize the intestine. Indeed, different antibiotic treatments caused distinct shifts in the intestinal microbiota prior to infection. Through fluorescence in situ hybridization, terminal restriction fragment length polymorphism, and real-time PCR, we showed that there is a strong correlation between the intestinal microbiota composition before infection and susceptibility to Salmonella-induced colitis. Members of the Bacteroidetes phylum were present at significantly higher levels in mice resistant to colitis. Further analysis revealed that Porphyromonadaceae levels were also increased in these mice. Conversely, there was a positive correlation between the abundance of Lactobacillus sp. and predisposition to colitis. Our data suggests that different members of the microbiota might be associated with S. Typhimurium colonization and colitis. Dissecting the mechanisms involved in resistance to infection and inflammation will be critical for the development of

  12. Nicotine Inhibits Clostridium difficile Toxin A-Induced Colitis but Not Ileitis in Rats

    Science.gov (United States)

    Vigna, Steven R.

    2016-01-01

    Nicotine is protective in ulcerative colitis but not Crohn's disease of the small intestine, but little is known about the effects of nicotine on Clostridium difficile toxin A-induced enteritis. Isolated ileal or colonic segments in anesthetized rats were pretreated with nicotine bitartrate or other pharmacological agents before intraluminal injection of toxin A. After 3 hours, the treated segments were removed and inflammation was assessed. Nicotine biphasically inhibited toxin A colitis but not ileitis. Pretreatment with the nicotinic receptor antagonist, hexamethonium, blocked the effects of nicotine. Pretreating the colonic segments with hexamethonium before toxin A administration resulted in more inflammation than seen with toxin A alone, suggesting that a tonic nicotinic anti-inflammatory condition exists in the colon. Nicotine also inhibited toxin A-induced increased colonic concentrations of the TRPV1 (transient receptor potential vanilloid subtype 1) agonist, leukotriene B4 (LTB4), and release of the proinflammatory neuropeptide, substance P. Pretreatment with nicotine did not protect against direct TRPV1-mediated colitis caused by intraluminal capsaicin. Nicotinic cholinergic receptors tonically protect the colon against inflammation and nicotine inhibits toxin A colitis but not toxin A ileitis in rats in part by inhibition of toxin A-induced activation of TRPV1 by endogenous TRPV1 agonists such as LTB4. PMID:26881175

  13. Somatostatin does not attenuate intestinal injury in dextran sodium sulphate-induced subacute colitis

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    J. D. van Bergeijk

    1998-01-01

    Full Text Available From several in vitro and in vivo studies involvement of som atostatin (SMS in intestinal inflammation emerge. Acute colitis induced in rats is attenuated by the long-acting SMS analogue octreotide. We studied the potential beneficial effect of SMS on non-acute experimental colitis. BALB/c mice received either saline, SMS-14 (36 or 120 μg daily or octreotide (3 μg daily subcutaneously delivered by implant osmotic pumps. A non-acute colitis was induced by administration of dextran sodium sulphate (DSS 10% in drinking water during 7 days. DSS evoked a mild, superficial pancolitis, most characterized by mucosal ulceration and submucosal influx of neutrophils. Neither SMS-14 nor octreotide reduced mucosal inflammatory score or macroscopical disease activity, although reduction of intestinal levels of interleukin1 β (IL-1 β, IL-6 and IL-10 during DSS was augmented both by SMS and octreotide. A slight increase of neutrophil influx was seen during SMS administration in animals not exposed to DSS. In conclusion, SMS or its long-acting analogue did not reduce intestinal inflammation in non-acute DSS-induced colitis. According to the cytokine profile observed, SMS-14 and octreotide further diminished the reduction of intestinal macrophage and Th2 lymphocyte activity.

  14. Effects of Rhizophora mangle on Experimental Colitis Induced by TNBS in Rats

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    Felipe Meira de Faria

    2012-01-01

    Full Text Available Male Unib-WH rats were pretreated for two weeks with butanolic (BuOH and ethyl acetate (EtOAc fractions. Colitis was induced by rectal administration of TNBS, the treatment continued, and animals were sacrificed on day 7 after the TNBS administration. Phytochemical studies were performed in order to provide the characterization of the tannins present in the bark of R. mangle. Results showed that EtOAc fraction increased the levels of IL-10 (**P<0.01 and diminished the levels of TNF-α (***P<0.001 and IL-6 (**P<0.01. BuOH fraction reduced the MPO activity (**P<0.01 and levels of TBARS (***P<0.001; it also increased COX-1 expression, diminished the levels of TNF-α (***P<0.001, and increased the levels of IL-12 (***P<0.001. Besides, both treatments augmented the levels of GSH (*P<0.05, the activity of GSH-Px (**P<0.01 for BuOH fraction and ***P<0.001 for EtOAc fraction, and CAT (**P<0.01. In conclusion, both treatments ameliorated the injury induced by TNBS through different mechanisms, probably by their chemical composition which directed its activity into an antioxidant or anti-inflammatory response, leading to an immune modulation.

  15. Negative regulation of DSS-induced experimental colitis by PILRα.

    Science.gov (United States)

    Kishida, Kazuki; Kohyama, Masako; Kurashima, Yosuke; Kogure, Yuta; Wang, Jing; Hirayasu, Kouyuki; Suenaga, Tadahiro; Kiyono, Hiroshi; Kunisawa, Jun; Arase, Hisashi

    2015-06-01

    Inflammatory bowel disease is thought to be a complex multifactorial disease, in which an increased inflammatory response plays an important role. Paired immunoglobulin-like type 2 receptor α (PILRα), well conserved in almost all mammals, is an inhibitory receptor containing immunoreceptor tyrosine-based inhibitory motifs in the cytoplasmic domain. PILRα is mainly expressed on myeloid cells and plays an important role in the regulation of inflammation. In the present study, we investigated the function of PILRα in inflammatory bowel disease using PILRα-deficient mice. When mice were orally administered dextran sulfate sodium (DSS), colonic mucosal injury and inflammation were significantly exacerbated in DSS-treated PILRα-deficient mice compared with wild-type (WT) mice. Flow cytometric analysis revealed that neutrophil and macrophage cell numbers were higher in the colons of DSS-treated PILRα-deficient mice than in those of WT mice. Blockade of CXCR2 expressed on neutrophils using a CXCR2 inhibitor decreased the severity of colitis observed in PILRα-deficient mice. These results suggest that PILRα negatively regulates inflammatory colitis by regulating the infiltration of inflammatory cells such as neutrophils and macrophages.

  16. Dietary uptake of Wedelia chinensis extract attenuates dextran sulfate sodium-induced colitis in mice.

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    Yuh-Ting Huang

    Full Text Available SCOPE: Traditional medicinal herbs are increasingly used as alternative therapies in patients with inflammatory diseases. Here we evaluated the effect of Wedelia chinensis, a medicinal herb commonly used in Asia, on the prevention of dextran sulfate sodium (DSS-induced acute colitis in mice. General safety and the effect of different extraction methods on the bioactivity of W. chinensis were also explored. METHODS AND RESULTS: C57BL/6 mice were administrated hot water extract of fresh W. chinensis (WCHF orally for one week followed by drinking water containing 2% DSS for nine days. WCHF significantly attenuated the symptoms of colitis including diarrhea, rectal bleeding and loss of body weight; it also reduced the shortening of colon length and histopathological damage caused by colonic inflammation. Among four W. chinensis extracts prepared using different extraction techniques, WCHF showed the highest anti-colitis efficacy. Analyses of specific T-cell regulatory cytokines (TNF-α, IL-4, IFN-γ, IL-17, TGF-β, IL-12 revealed that WCHF treatment can suppress the Th1 and Th17, but not Th2, responses in colon tissues and dendritic cells of DSS-induced colitis mice. A 28-day subacute toxicity study showed that daily oral administration of WCHF (100, 500, 1000 mg/kg body weight was not toxic to mice. CONCLUSION: Together, our findings suggest that specific extracts of W. chinensis have nutritional potential for future development into nutraceuticals or dietary supplements for treatment of inflammatory bowel disease.

  17. Healing Acceleration of Acetic Acid-induced Colitis by Marigold (Calendula officinalis) in Male Rats

    OpenAIRE

    Nader Tanideh; Akram Jamshidzadeh; Masood Sepehrimanesh; Masood Hosseinzadeh; Omid Koohi-Hosseinabadi; Asma Najibi; Mozhdeh Raam; Sajad Daneshi; Seyedeh-Leili Asadi-Yousefabad

    2016-01-01

    Background/Aim: Ulcerative colitis (UC) is a type of chronic inflammatory bowel disease with unknown etiology. Several therapeutic strategies such as consumption of medicinal plants have been used for its treatment. The aim of this study was to evaluate healing effects of Calendula officinalis hydroalcoholic extract in experimentally induced UC in rat. Materials and Methods: Ninety-six rats, weighing 200 ± 20 g, were randomly divided into eight equal groups. UC induced by 3% acetic acid and o...

  18. Attenuation of dextran sodium sulphate induced colitis in matrix metalloproteinase-9 deficient mice

    Institute of Scientific and Technical Information of China (English)

    Alfredo Santana; Carlos Medina; Maria Iristina Paz-Cabrera; Federico Díaz-Gonzalez; Esther Farré; Antonio Salas; Marek W Radomski; Enrique Quintero

    2006-01-01

    AIM: To study whether matrix metalloproteinase-9(MMP-9) is a key factor in epithelial damage in the dextran sodium sulphate (DSS) model of colitis in mice.METHODS: MMP-9-deficient and wild-type (wt)mice were given 5% DSS in drinking water for 5 dfollowed by recovery up to 7 d. On d 5 and 12 after induction of colitis, gelatinases,MMP-2 and MMP-9,were measured in homogenates of colonic tissue by zymography and Western blot, whereas Tissue inhibitor of metalloproteinases (TIMPs) were measured by reverse zymography. The gelatinolytic activity was also determined in supernatants of polymorphonuclear leukocytes (PMN) isolated from mice blood. Moreover,intestinal epithelial cells were stimulated with TNF-α to study whether these cells were able to produce MMPs.Finally, colonic mucosal lesions were measured by microscopic examination.RESULTS: On d 5 of colitis, the activity of MMP-9 was increased in homogenates of colonic tissues (0.24±0.1 vs 21.3±6.4,P<0.05) and PMN from peripheral blood in wt (0.5±0.1 vs 10.4±0.7,P<0.05), but not in MMP-9-deficient animals. The MMP-9 activity was also up-regulated by TNF-α in epithelial intestinal cells (2.5±0.5 vs 14.7±3.0, P<0.05). Although colitis also led to increase of TIMP-1 activity, the MMP-9/TIMP-1 balance remained elevated. Finally, in the MMP-9-deficient colitic mice both the extent and severity of intestinal epithelial injury were significantly attenuated when compared with wt mice.CONCLUSION: We conclude that DSS induced colitis is markedly attenuated in animals lacking MMP-9. This suggests that intestinal injury induced by DSS is modulated by MMP-9 and that inhibition of this gelatinase may reduce inflammation.

  19. Oat β-glucan ameliorates dextran sulfate sodium (DSS)-induced ulcerative colitis in mice.

    Science.gov (United States)

    Liu, Bo; Lin, Qinlu; Yang, Tao; Zeng, Linna; Shi, Limin; Chen, Yaya; Luo, Feijun

    2015-11-01

    Ulcerative colitis is a major inflammatory bowel disease (IBD), characterized by inflammation within the gastrointestinal tract through chronic or relapsing immune system activation. The aim of this study is to investigate the potential protective effect of oat β-glucan (βG) against colitis induced by DSS in mice. Eighty mice were randomly divided into the control group (no DSS, no βG), DSS group (DSS only), DSS + L-βG group (DSS plus 500 mg per kg βG), and DSS + H-βG group (DSS plus 1000 mg per kg βG). Compared with the DSS group, administration of βG significantly reduced clinical symptoms with less weight loss, diarrhea and shortening of the colon, the severity of colitis was significantly inhibited as evidenced by the reduced disease activity index (DAI) and degree of histological damage in colon. Moreover, treatment with βG not only decreased myeloperoxidase activity (MPO), and nitric oxide (NO) and malondialdehyde (MDA) levels, but also inhibited mRNA and protein expression of pro-inflammatory factors such as TNF-α, IL-1β, IL-6 and iNOS. This suggests that oat βG in diet might exhibit an anti-inflammatory function against colitis through inhibition of expression of pro-inflammatory factors.

  20. MicroRNA155 is induced in activated CD4~+ T cells of TNBS-induced colitis in mice

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM:To investigate the expression of microRNA155(miRNA155)in trinitrobenzene sulphonic acid(TNBS)induced colitis and the relationship between miRNA155 and tumor necrosis factor(TNF)expressions.METHODS:In TNBS colitis mice,miRNA155 and TNF mRNA expressions were measured in colons and CD4 + T cells of draining lymph nodes(LNs).CD4 + T cells were cultured in vitro with or without anti-CD3/CD28 antibody,and the expressions of miRNA155 and TNF mRNA in cells and TNF concentration in culture media were examined.RE...

  1. Local chemerin levels are positively associated with DSS-induced colitis but constitutive loss of CMKLR1 does not protect against development of colitis.

    Science.gov (United States)

    Dranse, Helen J; Rourke, Jillian L; Stadnyk, Andrew W; Sinal, Christopher J

    2015-08-01

    Inflammatory bowel disease (IBD) is a family of disorders including ulcerative colitis and Crohn's disease that are characterized by chronic and relapsing intestinal inflammation. Increased production of proinflammatory mediators, possibly combined with low expression of anti-inflammatory mediators, is thought to promote the development and progression of IBD. In the current study, we demonstrate that expression, secretion, and processing of chemerin, a potent chemoattractant for cells expressing chemokine-like receptor 1 (CMKLR1), increased in the cecum and colon along a gradient positively associated with the severity of inflammation in dextran sodium sulfate (DSS)-induced colitis. We also show that levels of circulating bioactive chemerin increased following DSS treatment. At both 6-8 and 14-16 weeks of age, CMKLR1 knockout mice developed signs of clinical illness more slowly than wild type and had changes in circulating cytokine levels, increased spleen weight, and increased local chemerin secretion following DSS treatment. However, knockout mice ultimately developed similar levels of clinical illness and local inflammation as wild type. Finally, contrary to previous reports, intraperitoneal injection of bioactive chemerin had no effect on the severity of DSS-induced colitis. This suggests that local chemerin levels have a greater impact than circulating levels in the pathogenesis of colitis. Considered altogether, bioactive chemerin represents a novel biomarker for IBD severity, although strategies to modulate endogenous chemerin signaling other than chronic CMKLR1 loss are necessary in order to exploit chemerin as a therapeutic target for the treatment of IBD.

  2. Amelioration of dextran sodium sulfate-induced colitis in mice by Rhodobacter sphaeroides extract.

    Science.gov (United States)

    Liu, Wen-Sheng; Chen, Man-Chin; Chiu, Kuo-Hsun; Wen, Zhi-Hong; Lee, Che-Hsin

    2012-01-01

    Bacteria can produce some compounds in response to their environment. These compounds are widely used in cosmetic and pharmaceutical applications. Some probiotics have immunomodulatory activities and modulate the symptoms of several diseases. Autoimmune diseases represent a complex group of conditions that are thought to be mediated through the development of autoreactive immunoresponses. Inflammatory bowel disease (IBD) is common autoimmune disease that affects many individuals worldwide. Previously, we found that the extracts of Rhodobacter sphaeroides (Lycogen) inhibited nitric oxide production and inducible nitric-oxide synthase expression in activated macrophages. In this study, the effect of Lycogen, a potent anti-inflammatory agent, was evaluated in mice with dextran sodium sulfate (DSS)-induced colitis. Oral administration of Lycogen reduced the expressions of proinflammatory cytokines (tumor necrosis factor-α and interleukin-1β) in female BABL/c mice. In addition, the increased number of bacterial flora in the colon induced by DSS was amelirated by Lycogen. The histological score of intestinal inflammation in 5% DSS-treated mice after oral administration of Lycogen was lower than that of control mice. Meanwhile, Lycogen dramatically prolonged the survival of mice with severe colitis. These findings identified that Lycogen is an anti-inflammatory agent with the capacity to ameliorate DSS-induced colitis. PMID:23159923

  3. Baicalin attenuates TNBS-induced colitis in rats by modulating the Th17/Treg paradigm.

    Science.gov (United States)

    Zou, Ying; Dai, Shi-Xue; Chi, Hong-Gang; Li, Tao; He, Zhi-Wei; Wang, Jian; Ye, Cai-Guo; Huang, Guo-Liang; Zhao, Bing; Li, Wen-Yang; Wan, Zheng; Feng, Jin-Shan; Zheng, Xue-Bao

    2015-10-01

    Baicalin, a flavonoid, has a wide range of pharmacological properties, including immunomodulation. The objective of this study was to investigate the effect of baicalin on the balance of T helper 17 (Th17) and regulatory T (Treg) cells in a colitis model. The rat colitis model was induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS). Baicalin (10 ml/kg, each) or mesalazine (positive control) was then administered orally for 7 days. Inflammatory and immunological responses were evaluated by pathology, enzyme-linked immunosorbent assay, real-time polymerase chain reaction, western blot analysis, and flow cytometry. Our study showed that baicalin not only significantly attenuated TNBS-induced colitis by reducing the disease activity index as well as macroscopic and microscopic scores, but it also improved the weight loss and shortening of the colon. Baicalin treatment also induced a significant decrease in the levels of inflammatory mediators, including the myeloperoxidase activity, the levels of tumor necrosis factor α, IL-1β, and Th1-related cytokines IL-12 and IFN-γ. Furthermore, the beneficial effects of baicalin seem to be associated with regulation of the Th17 and Treg paradigm. We found that administration of baicalin significantly downregulated the number of Th17 cells and the levels of Th17-related cytokines (IL-17 and IL-6) and retinoic acid receptor-related orphan receptor γt. In contrast, there was an increase in Treg cells numbers, Treg-related cytokines transforming growth factor-β and IL-10, and forkhead box P3. Our results suggest that the anti-inflammatory effect of baicalin may be linked to modulation of the balance between Th17 and Treg cells in TNBS-induced ulcerative colitis. PMID:25269538

  4. Protective Effect of Amphipterygium adstringens Extract on Dextran Sulphate Sodium-Induced Ulcerative Colitis in Mice

    Science.gov (United States)

    Rodriguez-Canales, Mario; Jimenez-Rivas, Ruben; Canales-Martinez, Maria Margarita; Garcia-Lopez, Ana Judith; Rivera-Yañez, Nelly; Nieto-Yañez, Oscar; Ledesma-Soto, Yadira; Sanchez-Torres, Luvia Enid; Rodriguez-Sosa, Miriam; Terrazas, Luis Ignacio

    2016-01-01

    Amphipterygium adstringens is an endemic species in Mexico commonly known as “cuachalalate.” Healers to treat gastritis, gastric ulcers, and gastrointestinal cancer have traditionally used the bark. We investigated the effects of alcoholic extract of A. adstringens (AaEE) in DSS-induced colitis in mice. The protective effect of AaEE was determined at 200 mg/kg by oral gavage for 10 days. We determine the effect of AaEE on clinical features (disease activity index), antioxidants, anti-inflammatory, and immunomodulatory activities in relation to the activity of SOD, CAT, and GPx, levels of proinflammatory cytokines, and changes both macroscopic and microscopic of the colonic mucosa. AaEE significantly reduced the inflammation of colon and significantly increased SOD and GPx activities. AaEE also significantly decreased TNF-α, IFN-γ, and IL-1β cytokine levels compared to DSS-treated mice and reduced both infiltration of inflammatory cells and the mucosal damage in colon. The results suggested the protective potential of AaEE in DSS-induced colitis and this might be attributed to its phytochemicals compounds that have been found to induce a wide spectrum of activities such as reduction in oxidative stress, suppression of inflammation, modulating numerous signal transduction pathways, and induction of apoptosis. The findings of this study suggest that AaEE has substantial potential for the treatment of inflammatory colitis. PMID:27635116

  5. Protective Effect of Amphipterygium adstringens Extract on Dextran Sulphate Sodium-Induced Ulcerative Colitis in Mice

    Directory of Open Access Journals (Sweden)

    Mario Rodriguez-Canales

    2016-01-01

    Full Text Available Amphipterygium adstringens is an endemic species in Mexico commonly known as “cuachalalate.” Healers to treat gastritis, gastric ulcers, and gastrointestinal cancer have traditionally used the bark. We investigated the effects of alcoholic extract of A. adstringens (AaEE in DSS-induced colitis in mice. The protective effect of AaEE was determined at 200 mg/kg by oral gavage for 10 days. We determine the effect of AaEE on clinical features (disease activity index, antioxidants, anti-inflammatory, and immunomodulatory activities in relation to the activity of SOD, CAT, and GPx, levels of proinflammatory cytokines, and changes both macroscopic and microscopic of the colonic mucosa. AaEE significantly reduced the inflammation of colon and significantly increased SOD and GPx activities. AaEE also significantly decreased TNF-α, IFN-γ, and IL-1β cytokine levels compared to DSS-treated mice and reduced both infiltration of inflammatory cells and the mucosal damage in colon. The results suggested the protective potential of AaEE in DSS-induced colitis and this might be attributed to its phytochemicals compounds that have been found to induce a wide spectrum of activities such as reduction in oxidative stress, suppression of inflammation, modulating numerous signal transduction pathways, and induction of apoptosis. The findings of this study suggest that AaEE has substantial potential for the treatment of inflammatory colitis.

  6. Curcumin-attenuated trinitrobenzene sulphonic acid induces chronic colitis by inhibiting expression of cyclooxygenase-2

    Institute of Scientific and Technical Information of China (English)

    Hua Jiang; Chang-Sheng Deng; Ming Zhang; Jian Xia

    2006-01-01

    AIM: To explore the possible mechanisms of curcumin in rat colitis induced by trinitrobenzene sulfonic (TNBS) acid. METHODS: Rats with TNBS acid-induced colitis were treated with curcumin (30 mg/kg or 60 mg/kg per day ip). Changes of body weight and histological scores as well as survival rate were evaluated. Leukocyte infiltration was detected by myeloperoxidase (MPO)activity assay. The expression of cyclooxygenase-2(COX-2) was detected by RT-PCR and Western blot.Inflammation cytokines were determined by RT-PCR.Local concentration of prostaglandin E2 (PGE2) in colon mucosa was determined by ELISA.RESULTS: Curcumin improved survival rate and histological image, decreased the macroscopic scores and MPO activity. Also curcumin reduced the expression of COX-2 and inflammation cytokines. In addition,treatment with curcumin increased the PGE2 level.CONCLUSION: Curcumin has therapeutic effects on TNBS acid-induced colitis, the mechanisms seem to be related to COX-2 inhibition and PGE2 improvement.

  7. Protective Effect of Amphipterygium adstringens Extract on Dextran Sulphate Sodium-Induced Ulcerative Colitis in Mice.

    Science.gov (United States)

    Rodriguez-Canales, Mario; Jimenez-Rivas, Ruben; Canales-Martinez, Maria Margarita; Garcia-Lopez, Ana Judith; Rivera-Yañez, Nelly; Nieto-Yañez, Oscar; Ledesma-Soto, Yadira; Sanchez-Torres, Luvia Enid; Rodriguez-Sosa, Miriam; Terrazas, Luis Ignacio; Rodriguez-Monroy, Marco Aurelio

    2016-01-01

    Amphipterygium adstringens is an endemic species in Mexico commonly known as "cuachalalate." Healers to treat gastritis, gastric ulcers, and gastrointestinal cancer have traditionally used the bark. We investigated the effects of alcoholic extract of A. adstringens (AaEE) in DSS-induced colitis in mice. The protective effect of AaEE was determined at 200 mg/kg by oral gavage for 10 days. We determine the effect of AaEE on clinical features (disease activity index), antioxidants, anti-inflammatory, and immunomodulatory activities in relation to the activity of SOD, CAT, and GPx, levels of proinflammatory cytokines, and changes both macroscopic and microscopic of the colonic mucosa. AaEE significantly reduced the inflammation of colon and significantly increased SOD and GPx activities. AaEE also significantly decreased TNF-α, IFN-γ, and IL-1β cytokine levels compared to DSS-treated mice and reduced both infiltration of inflammatory cells and the mucosal damage in colon. The results suggested the protective potential of AaEE in DSS-induced colitis and this might be attributed to its phytochemicals compounds that have been found to induce a wide spectrum of activities such as reduction in oxidative stress, suppression of inflammation, modulating numerous signal transduction pathways, and induction of apoptosis. The findings of this study suggest that AaEE has substantial potential for the treatment of inflammatory colitis. PMID:27635116

  8. Dual role of endogenous serotonin in 2,4,6-trinitrobenzene sulfonic acid-induced colitis

    Directory of Open Access Journals (Sweden)

    Alberto eRapalli

    2016-03-01

    Full Text Available Background and Aims: Changes in gut serotonin content have been described in Inflammatory Bowel Disease and in different experimental models of colitis: the critical role of this monoamine in the pathogenesis of chronic gastrointestinal inflammation is gradually emerging. Aim of the present study was to evaluate the contribution of endogenous serotonin through the activation of its specific receptor subtypes to the local and systemic inflammatory responses in an experimental model of Inflammatory Bowel Disease. Methods: Colitis was induced by intrarectal 2,4,6-TriNitroBenzene Sulfonic acid in mice subacutely treated with selective antagonists of 5-HT1A (WAY100135, 5-HT2A (Ketanserin, 5-HT3 (Ondansetron, 5-HT4 (GR125487, 5-HT7 (SB269970 receptors and with 5-HT1A agonist 8-Hydroxy-2-(di-n-propylaminotetralin. Results: Blockade of 5-HT1A receptors worsened TNBS-induced local and systemic neutrophil recruitment while 5-HT1A agonist delayed and mitigated the severity of colitis, counteracting the increase in colonic 5-HT content. On the contrary, blockade of 5-HT2A receptors improved global health conditions, reduced colonic morphological alterations, down-regulated neutrophil recruitment, inflammatory cytokines levels and colonic apoptosis. Antagonism of 5-HT3, 5-HT4 and 5-HT7 receptor sites did not remarkably affect the progression and outcome of the pathology or only slightly improved it.Conclusions: The prevailing deleterious contribution given by endogenous serotonin to inflammation in TNBS-induced colitis is seemingly mediated by 5-HT2A and, to a lesser extent, by 5-HT4 receptors and coexists with the weak beneficial effect elicited by 5-HT1A stimulation. These findings suggest how only a selective interference with 5-HT pro-inflammatory actions may represent an additional potential therapeutic option for intestinal inflammatory disorders.

  9. Excretory/secretory products from Trichinella spiralis adult worms ameliorate DSS-induced colitis in mice.

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    Xiaodi Yang

    Full Text Available BACKGROUND: Many evidences show the inverse correlation between helminth infection and allergic or autoimmune diseases. Identification and characterization of the active helminth-derived products responsible for the beneficial effects on allergic or inflammatory diseases will provide another feasible approach to treat these diseases. METHODS AND FINDINGS: Colitis was induced in C57BL/6 mice by giving 3% DSS orally for 7 days. During this period, the mice were treated daily with the excretory/secretory products from T. spiralis adult worms (AES intraperitoneally. The severity of colitis was monitored by measuring body weight, stool consistency or bleeding, colon length and inflammation. To determine the T. spiralis AES product-induced immunological response, Th1, Th2, Th17 and regulatory cytokine profiles were measured in lymphocytes isolated from colon, mesenteric lymph nodes (MLN, and the spleen of treated mice. The CD4+ CD25+ FOXP3+ regulatory T cells (Tregs were also measured in the spleens and MLN of treated mice. Mice treated with AES significantly ameliorated the severity of the DSS-induced colitis indicated by the reduced disease manifestations, improved macroscopic and microscopic inflammation correlated with the up-regulation of Treg response (increased regulatory cytokines IL-10, TGF-beta and regulatory T cells and down-regulation of pro-inflammatory cytokines (IFN-gamma, IL-6 and IL-17 in the spleens, MLN and colon of treated mice. CONCLUSIONS: Our results provide direct evidences that T. spiralis AES have a therapeutic potential for alleviating inflammatory colitis in mice. This effect is possibly mediated by the immunomodulation of regulatory T cells to produce regulatory and anti-inflammatory cytokines and inhibit pro-inflammatory cytokines.

  10. Effects of Rhizophora mangle on Experimental Colitis Induced by TNBS in Rats.

    Science.gov (United States)

    de Faria, Felipe Meira; Luiz-Ferreira, Anderson; Socca, Eduardo Augusto Rabelo; de Almeida, Ana Cristina Alves; Dunder, Ricardo José; Manzo, Luis Paulo; da Silva, Marcelo Aparecido; Vilegas, Wagner; Rozza, Ariane Leite; Pellizzon, Cláudia Helena; Dos Santos, Lourdes Campaner; Souza Brito, Alba Regina Monteiro

    2012-01-01

    Male Unib-WH rats were pretreated for two weeks with butanolic (BuOH) and ethyl acetate (EtOAc) fractions. Colitis was induced by rectal administration of TNBS, the treatment continued, and animals were sacrificed on day 7 after the TNBS administration. Phytochemical studies were performed in order to provide the characterization of the tannins present in the bark of R. mangle. Results showed that EtOAc fraction increased the levels of IL-10 (∗∗P < 0.01) and diminished the levels of TNF-α (∗∗∗P < 0.001) and IL-6 (∗∗P < 0.01). BuOH fraction reduced the MPO activity (∗∗P < 0.01) and levels of TBARS (∗∗∗P < 0.001); it also increased COX-1 expression, diminished the levels of TNF-α (∗∗∗P < 0.001), and increased the levels of IL-12 (∗∗∗P < 0.001). Besides, both treatments augmented the levels of GSH (∗P < 0.05), the activity of GSH-Px (∗∗P < 0.01 for BuOH fraction and ∗∗∗P < 0.001 for EtOAc fraction), and CAT (∗∗P < 0.01). In conclusion, both treatments ameliorated the injury induced by TNBS through different mechanisms, probably by their chemical composition which directed its activity into an antioxidant or anti-inflammatory response, leading to an immune modulation. PMID:23056142

  11. Anti-inflammatory effect of Moringa oleifera Lam. seeds on acetic acid-induced acute colitis in rats

    OpenAIRE

    Mohsen Minaiyan; Gholamreza Asghari; Diana Taheri; Mozhgan Saeidi; Salar Nasr-Esfahani

    2014-01-01

    Objective: Anti-inflammatory, immuno-modulatory, and antioxidant properties of Moringa oleifera Lam. suggest that it might have beneficial effects on colitis. The present study was performed to investigate the anticolitis effect of Moringa oleifera seeds hydro-alcoholic extract (MSHE) and its chloroform fraction (MCF) on acetic acid-induced colitis in rats. Materials and Methods: Both MSHE and MCF with three increasing doses (50, 100, and 200 mg/kg) were administered orally to separate groups...

  12. The Effect of Calendula Officinalis in Therapy of Acetic Acid Induced Ulcerative Colitis in Dog as an Animal Model

    OpenAIRE

    Mehrabani, D; M. Ziaei; Hosseini, S.V; Ghahramani, L; Bananzadeh, A M; Ashraf, M. J.; Amini, A; Amini, M; Tanideh, N

    2011-01-01

    Background In patients with ulcerative colitis (UC), the repeated cycle of injury and repair of intestinal mucosa has been reported to increase the risk of colon cancer. So, a safe and efficient therapy is required for the treatment and prophylaxis for the disease.This study aims to investigate the efficacy of Calendula officinalis extract in treatment of experimentally induced ulcerative colitis in dog animal model. Methods During fall 2010, 10 out-bred female German dogs (1-2 years old; wei...

  13. COMPARATIVE EFFICACY OF DIFFERENT REFERENCE DRUGS ON TRINITROBENZENESULFONIC ACID-INDUCED ULCERATIVE COLITIS IN THE RAT MODEL

    OpenAIRE

    P.S.Venkatesan; M. Deecaraman; M. Vijayalakshmi

    2013-01-01

    Crohn’s disease and Ulcerative colitis were chronic inflammatory disorders of the bowel categorized as inflammatory bowel diseases. Trinitrobenzene sulfonic acid (TNBS)-induced colitis was one of the most common methods for studying inflammatory bowel disease in animal models. Several factors may, however, affect its reproducibility, rate of animal mortality, and macroscopic and histopathological outcomes.The current study was undertaken with the objective to validate the main contributing fa...

  14. Anti-inflammatory effect of Prunus armeniaca L. (Apricot) extracts ameliorates TNBS-induced ulcerative colitis in rats

    OpenAIRE

    Minaiyan, M.; Ghannadi, A.; Asadi, M; Etemad, M.; Mahzouni, P.

    2014-01-01

    Prunus armeniaca L. (Apricot) is a tree cultivated in different parts of the world. Apricot kernel as a good dietary supplement has shown antioxidant, anti-inflammatory and other pharmacologic properties which suggest that it may be functional as an anticolitis agent. In this study we evaluated the effects of apricot kernel extract and oil on ulcerative colitis in rats. Rats were fasted for 36 h before the experiment. Colitis was induced by intra-rectal instillation of 50 mg/kg trinitrobenzen...

  15. Antibody to eosinophil cationic protein suppresses dextran sulfate sodium-induced colitis in rats

    Institute of Scientific and Technical Information of China (English)

    Kazuko Shichijo; Kazuya Makiyama; Chun-Yang Wen; Mutsumi Matsuu; Toshiyuki Nakayama; Masahiro Nakashima; Makoto Ihara; Ichiro Sekine

    2005-01-01

    AIM: To produce an antibody against rat eosinophil cationic protein (ECP) and to examine the effects of the antibody in rats with dextran sulfate sodium (DSS)-induced colitis.METHODS: An antibody was raised against rat ECP. Rats were treated with 3% DSS in drinking water for 7 d and received the antibody or normal serum. The colons were exarmined histologically and correlated with clinical symptoms.Immunohistochemistry and Western blot analysis were estimated as a grade of inflammation.RESULTS: The ECP antibody stained the activated eosinophils around the injured crypts in the colonic mucosa.Antibody treatment reduced the severity of colonic ulceration and acute clinical symptoms (diarrhea and/or blood-stained stool). Body weight gain was significantly greater and the colon length was significantly longer in anti-ECP-treated rats than in normal serum-treated rats. Expression of ECP in activated eosinophils was associated with the presence of erosions and inflammation. The number of Ki-67-positive cells in the regenerated surface epithelium increased in anti-ECP-treated rats compared with normal serum-treated rats. Western blot analysis revealed reduced expression of macrophage migration inhibitory factor (MIF) in anti-ECP-treated rats.CONCLUSION: Our results indicate that treatment with ECP antibody, improved DSS-induced colitis in rats, possibly by increasing the regenerative activity of the colonic epithelium and downregulation of the immune response,and suggest that anti-ECP may promote intestinal wound healing in patients with ulcerative colitis (UC).

  16. The effects of colloidal bismuth tartrate on colitis induced by immune-complex in rabbits

    Institute of Scientific and Technical Information of China (English)

    Li Zheng; Shu Xian Wang; Zhen Qiang Gao

    2000-01-01

    AIM To observe the therapeutic effect of colloidal bismuth tartrate in an animal colitis model.METHODS Immune-complex colitis was induced in groups of rabbits by formalin, and two hours later0.85 mL heat-aggregated rabbit IgG was given intravenously through the ear cannula. Animals wereintracolonically treated with colloidal bismuth tartrate (BITNAL), and its effect was compared withsulfasalazine (SASP), indomethacin (IND) and bifidobiogen (BIFG). Animals were killed, the mucosalappearance was scored (0-4), and tissue saved for histological studies, the number of neutrophils present ininflamed colonic tissue was quantitated by the myeloperoxidase (MPO) activity assay, the production oflipoxygenase and cyclo-oxygenase products was monitored and eicosanoid production were assayed byincubation colonic specimens and the media for prostaglandin E2(PGE2), leukotriene (LTB4), thromboxaneB2(TXPe) were examined by radiommunoassay.RESULTS Immune-complex colitis was induced by formalin and IgG, colonic damage persisted for at least1 wk by macrography. Histologically, the inflammatory response included mucosal and submucosalinfiltration by polymorphonuclear leukocytes, macrophages, lymphocytes and fibroblasts, the macroscopic,persent 2 wk after IgG, was correlated with greatly increased PGE2, LTB4 and TXB2 compared with levels incontrols. Treatment with BITNAL (500 mg/kg) resulted in a lowered inflammation index, lowered MPOactivity and inhibited the increased formation of PGF-2, LTB4 and TXB2 by the inflamed colon, and IND(500 mg/kg) markedly inhibited prostanoid formation in both inflamed and control colon but did not reducetissue damage, SASP (500 mg/kg) also inhibited the formation of PGE2, LTB4 and TXB2 but the effectswere less marked. BIFG (400 mg/kg) did not significantly reduce the colonic injury and the media sythesizedby the rabbit colon.CONCLUSION BITAL provides better therapeutic effects in experimental colitis than anti-inflammatorydrug IND or SASP.

  17. Bifidobacterium breve attenuates murine dextran sodium sulfate-induced colitis and increases regulatory T cell responses.

    Directory of Open Access Journals (Sweden)

    Bin Zheng

    Full Text Available While some probiotics have shown beneficial effects on preventing or treating colitis development, others have shown no effects. In this study, we have assessed the immunomodulating effects of two probiotic strains, Lactobacillus rhamnosus (L. rhamnosus and Bifidobacterium breve (B. breve on T cell polarization in vitro, using human peripheral blood mononuclear cells (PBMC, and in vivo, using murine dextran sodium sulfate (DSS colitis model. With respect to the latter, the mRNA expression of T cell subset-associated transcription factors and cytokines in the colon was measured and the T helper type (Th 17 and regulatory T cell (Treg subsets were determined in the Peyer's patches. Both L. rhamnosus and B. breve incubations in vitro reduced Th17 and increased Th2 cell subsets in human PBMCs. In addition, B. breve incubation was also able to reduce Th1 and increase Treg cell subsets in contrast to L. rhamnosus. In vivo intervention with B. breve, but not L. rhamnosus, significantly attenuated the severity of DSS-induced colitis. In DSS-treated C57BL/6 mice, intervention with B. breve increased the expression of mRNA encoding for Th2- and Treg-associated cytokines in the distal colon. In addition, intervention with B. breve led to increases of Treg and decreases of Th17 cell subsets in Peyer's patches of DSS-treated mice. B. breve modulates T cell polarization towards Th2 and Treg cell-associated responses in vitro and in vivo. In vivo B. breve intervention ameliorates DSS-induced colitis symptoms and this protective effect may mediated by its effects on the T-cell composition.

  18. Recombinant human MFG-E8 ameliorates colon damage in DSS- and TNBS-induced colitis in mice.

    Science.gov (United States)

    Zhang, Yinzhong; Brenner, Max; Yang, Weng-Lang; Wang, Ping

    2015-05-01

    Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the digestive system and typically requires lifelong medical care. Recombinant human MFG-E8 (rhMFG-E8) is a 364-amino acid protein, which promotes apoptotic cell clearance and reduces inflammation. This study investigates the therapeutic effect of rhMFG-E8 on two well-established mouse models of IBD. Acute mucosal injury leading to colitis was caused by exposing C57BL/6 mice to 4% dextran sodium sulfate (DSS) in the drinking water over 7 days, and BALB/c mice to a single intrarectal dose of 2.75 mg of 2,4,6-trinitrobenzene sulfonic acid (TNBS). Upon clinical onset of colitis (day 2 in the DSS model and day 1 in the TNBS model), mice were treated with daily subcutaneous injections of rhMFG-E8 (60 or 120 μg/kg/day) or vehicle (saline) for 6 days. Treatment with rhMFG-E8 significantly attenuated colitis in both models in a dose-dependent way. Treatment of DSS-induced colitis with rhMFG-E8 (120 μg/kg/day) decreased weight loss by 59%, the colitis severity score by 71%, and colon shrinkage by 49% when compared with vehicle. Similarly, treatment of TNBS-induced colitis with rhMFG-E8 (120 μg/kg/day) decreased weight loss by 97%, the colitis severity score by 82%, and colon shrinkage by 62% when compared with vehicle. In both models, the colons of animals receiving rhMFG-E8 showed marked reduction in neutrophil infiltration, cytokine and chemokine expression, and apoptotic cell counts. In conclusion, rhMFG-E8 ameliorates DSS- and TNBS-induced colitis, suggesting that it has the potential to become a novel therapeutic agent for IBD.

  19. The influence of pretreatment with ghrelin on the development of acetic-acid-induced colitis in rats.

    Science.gov (United States)

    Maduzia, D; Matuszyk, A; Ceranowicz, D; Warzecha, Z; Ceranowicz, P; Fyderek, K; Galazka, K; Dembinski, A

    2015-12-01

    Ghrelin has been primarily shown to exhibit protective and therapeutic effect in the gut. Pretreatment with ghrelin inhibits the development of acute pancreatitis and accelerates pancreatic recovery in the course of this disease. In the stomach, ghrelin reduces gastric mucosal damage induced by ethanol, stress or alendronate, as well as accelerates the healing of acetic acid-induced gastric and duodenal ulcer. The aim of present studies was to investigate the effect of pretreatment with ghrelin on the development of acetic acid-induced colitis. Studies have been performed on male Wistar rats. Animals were treated intraperitoneally with saline (control) or ghrelin (4, 8 or 16 nmol/kg/dose). Saline or ghrelin was given twice: 8 and 1 h before induction of colitis. Colitis was induced by a rectal enema with 1 ml of 4% solution of acetic acid and the severity of colitis was assessed 1 or 24 hours after induction of inflammation. Rectal administration of acetic acid induced colitis in all animals. Damage of colonic wall was seen at the macroscopic and microscopic level. This effect was accompanied by a reduction in colonic blood flow and mucosal DNA synthesis. Moreover, induction of colitis significantly increased mucosal concentration of pro-inflammatory interleukin-1β (IL-1β), activity of myeloperoxidase and concentration of malondialdehyde (MDA). Mucosal activity of superoxide dismutase (SOD) was reduced. Pretreatment with ghrelin reduced the area and grade of mucosal damage. This effect was accompanied by an improvement of blood flow, DNA synthesis and SOD activity in colonic mucosa. Moreover, ghrelin administration reduced mucosal concentration of IL-1β and MDA, as well as decreased mucosal activity of myeloperoxidase. Administration of ghrelin protects the large bowel against the development of the acetic acid-induced colitis and this effect seems to be related to the ghrelin-evoked anti-inflammatory and anti-oxidative effects.

  20. Changes of CD8+CD28- T regulatory cells in rat model of colitis induced by 2,4-dinitrofluorobenzene

    Institute of Scientific and Technical Information of China (English)

    Wen-Bin Xiao; Yu-Lan Liu

    2003-01-01

    AIM: To determine the changes of CD8+ T subsets especially CD8+CD28- T regulatory cells in rat model of experimental colitis induced by 2,4-dinitrofiuorobenzene (DNFB).METHODS: The rat model of experimental colitis was induced by enema with DNFB. Ten days later, colonic intraepithelial and splenic lymphocytes were isolated from colitis animals (n=16) and controls (n=8). The proportion of CD8+ T cells, CD8+CD28+ T cells and CD8+CD28- T regulatory cells were determined by flow cytometry.RESULTS: The model of experimental colitis was successfully established by DNFB that was demonstrated by bloody diarrhea, weight loss and colonic histopathology. The proportion of CD8+ T cells in either splenic or colonic intraepithelial lymphocytes was not significantly different between colitis animals and controls (spleen: 34.6±7.24 % vs33.5±9.41%,colon: 14.0±8.93 % vs 18.0±4.06 %, P>0.05). But CD8+CD28-T regulatory cells from colitis animals were significantly more than those from controls (spleen: 11.3±2.26 % vs5.64±1.01%,colon: 6.50±5.37 % vs 1.07±0.65 %, P<0.05). In contrast,CD8+CD28+ T cells from colitis animals were less than those from controls (spleen: 23.3±6.14 % vs27.8±9.70 %, P=0.06;colon: 7.52±4.18 % vs 16.9±4.07 %, P<0.05). The proportion of CD8+CD28- T regulatory cells in splenic and colonintraepithelial CD8+ T cells from colitis animals was higher than that from controls (spleen: 33.3±5.49 % vs 18.4±7.26 %,colon: 46.0±14.3 % vs6.10±3.72 %, P<0.005).CONCLUSION: Experimental colitis of rats can be induced by DNFB with simplicity and good reproducibility. The proportion of CD8+CD28- T regulatory cells in rats with experimental colitis is increased, which may be associated with the pathogenesis of colitis.

  1. Augmented activity of the pelvic nerve afferent mediated by TRP channels in dextran sulfate sodium (DSS)-induced colitis of rats.

    Science.gov (United States)

    Makimura, Yukitoshi; Ito, Koichi; Kuwahara, Masayoshi; Tsubone, Hirokazu

    2012-08-01

    Enteritis has been recognized as a major symptom in domestic animals and human patients suffering from feed and food poisonings. The aim of the present study was to clarify the excitatory mechanism of the pelvic nerve afferent which may influence the occurrence of enteritis in response to nociceptive chemical stimuli of the colon in normal and abnormal rats with colitis induced by dextran sulfate sodium (DSS). The pelvic nerve afferent activity was markedly increased by colonic instillation of solution (0.5 ml) of acetic acid (5-25%) and capsaicin (100 μg/ml). The nerve activity was augmented by colonic instillation of capsaicin to a greater extent in rats with DSS-induced colitis than in normal control rats. This augmented activity by capsaicin was more prominent at one day (DSS-1) than at 8 day (DSS-8) after the administration of DSS. The increased nerve activity caused by capsaicin in DSS-1 and DSS-8 was significantly inhibited by pretreatment with ruthenium red, which is a nonselective inhibitor of TRP channels of unmyelinated C-fibers (nociceptors). In conclusion, it was elucidated that the nociceptive function of the pelvic nerve was largely elevated at one day after DSS-induced colitis and such increased function was mostly mediated by TRP channels.

  2. Increased presence of effector lymphocytes during Helicobacter hepaticus-induced colitis

    Institute of Scientific and Technical Information of China (English)

    Sarah J McCaskey; Elizabeth A Rondini; Jonathan F Clinthorne; Ingeborg M Langohr; Elizabeth M Gardner; Jenifer I Fenton

    2012-01-01

    AIM:To identify and characterize drosophila mothers against decapentaplegic (SMAD)3-dependent changes in immune cell populations following infection with HeliCobacter hepaticus (H.hepaticus).METHODS:SMAD3-/-(n =19) and colitis-resistant SMAD3+/-(n =24) mice (8-10 wk of age) were infected with H.hepaticus and changes in immune cell populations [T lymphocytes,natural killer (NK) cells,T regulatory cells] were measured in the spleen and mesenteric lymph nodes (MsLNs) at 0 d,3 d,7 d and 28 d post-infection using flow cytometry.Genotypedependent changes in T lymphocytes and granzyme B+ cells were also assessed after 28 d in proximal colon tissue using immunohistochemistry.RESULTS:As previously observed,SMAD3-/-,but not SMAD3+/-mice,developed colitis,peaking at 4 wk post-infection.No significant changes in T cell subsets were observed in the spleen or in the MsLNs between genotypes at any time point.However,CD4+ and CD8+/CD62L10 cells,an effector T lymphocyte population,as well as NK cells (NKp46/DX5+) were significantly higher in the MsLNs of SMAD3-/-mice at 7 d and 28 d post-infection.In the colon,a higher number of CD3+ cells were present in SMAD3-/-compared to SMAD3+/-mice at baseline,which did not significantly change during infection.However,the number of granzyme B+ cells,a marker of cytolytic lymphocytes,significantly increased in SMAD3-/-mice 28 d post-infection compared to both SMAD3+/-mice and to baseline values.This was consistent with more severe colitis development in these animals.CONCLUSION:Data suggest that defects in SMAD3signaling increase susceptibility to H.hepaticus-induced colitis through aberrant activation and/or dysregulation of effector lymphocytes.

  3. Prevention of Chronic Experimental Colitis Induced by Dextran Sulphate Sodium (DSS in Mice Treated with FR91

    Directory of Open Access Journals (Sweden)

    Valter R. M. Lombardi

    2012-01-01

    Full Text Available One of the main treatments currently used in humans to fight cancer is chemotherapy. A huge number of compounds with antitumor activity are present in nature, and many of their derivatives are produced by microorganisms. However, the search for new drugs still represents a main objective for cancer therapy, due to drug toxicity and resistance to multiple chemotherapeutic drugs. In animal models, a short-time oral administration of dextran sulfate sodium (DSS induces colitis, which exhibits several clinical and histological features similar to ulcerative colitis (UC. However, the pathogenic factors responsible for DSS-induced colitis and the subsequent colon cancer also remain unclear. We investigated the effect of FR91, a standardized lysate of microbial cells belonging to the Bacillus genus which has been previously shown to have significant immunomodulatory effects, against intestinal inflammation. Colitis was induced in mice during 5 weeks by oral administration 2% (DSS. Morphological changes in the colonic mucosa were evaluated by hematoxylin-eosin staining and immunohistochemistry methods. Adenocarcinoma and cryptal cells of the dysplastic epithelium showed cathenin-β, MLH1, APC, and p53 expression, together with increased production of IFN-γ. In our model, the optimal dose response was the 20% FR91 concentration, where no histological alterations or mild DSS-induced lesions were observed. These results indicate that FR91 may act as a chemopreventive agent against inflammation in mice DSS-induced colitis.

  4. Effects of Guchang Capsule on Dextran Sulphate Sodium-Induced Experimental Ulcerative Colitis in Mice

    Science.gov (United States)

    Liu, Baoshan; Liu, Tong; Wang, Xiaohong; Zheng, Xin; Wang, Hong; Ma, Lin

    2016-01-01

    Guchang capsule (GC) is a Chinese materia medica standardized product extracted from 15 Chinese traditional medical herbs and it has been clinically used in the treatment of intestinal disease. In this study, in order to extend the research of GC in intestinal disease, we were aiming to evaluate potential effects of GC on dextran sulphate sodium- (DSS-) induced murine experimental colitis and to elucidate the underlying mechanisms. GC treatment attenuated DSS-induced body weight loss and reduced the mortality. Moreover, GC treatment prevented DSS-induced colonic pathological damage; meanwhile it inhibited proinflammatory cytokines production in colon tissues. In vitro, GC significantly reduced LPS-induced proinflammatory cytokines production via inhibiting the activation of NF-κB in macrophage cells, and the expressions of several long noncoding RNAs (lncRNAs) which were reported in regulating NF-κB signaling pathway were obviously affected by adding GC into culture medium. In conclusion, our data suggested that administration of GC exhibits therapeutic effects on DSS-induced colitis partially through regulating the expression of NF-κB related lncRNAs in infiltrating immune cells. PMID:27313642

  5. Halofuginone reduces the inflammatory responses of DSS-induced colitis through metabolic reprogramming.

    Science.gov (United States)

    Liu, Jing; Xiao, Hai-Tao; Wang, Hong-Sheng; Mu, Huai-Xue; Zhao, Ling; Du, Jun; Yang, Depo; Wang, Dongmei; Bian, Zhao-Xiang; Lin, Shu-Hai

    2016-06-21

    Hypoxia and inflammation have been identified as the hallmarks of colitis, intertwined with metabolism. Here, we report that halofuginone (HF), an antiparasitic drug, attenuates dextran sulfate sodium (DSS)-induced colitis in mice, as represented by attenuating the disease activity index, inhibiting colonic shortening, ameliorating colonic lesions and histological signs of damage, reducing colonic myeloperoxidase activity, and suppressing the production of pro-inflammatory cytokines in colon tissue. Intriguingly, the hypoxia-inducible factor 1alpha (HIF-1α) and tumor necrosis factor alpha were also suppressed by HF treatment in colon tissues, exhibiting a tissue-specific effect. To further reveal the metabolic signatures upon HF treatment, mass spectrometry-based metabolomic analysis of the small molecular metabolites in liver, spleen and colon tissues was performed. As a result, we found that HF treatment counteracted the levels of acylcarnitines, including palmitoyl-l-carnitine, isobutyrylcarnitine, vaccenylcarnitine, and myristoylcarnitine, in colon tissues with DSS induction, but no significant change in the levels of acylcarnitines was observed in liver or spleen tissues. The metabolic signatures may indicate that incomplete fatty acid oxidation (FAO) in the colon could be restored upon HF treatment as the tissue-specific metabolic characterization. Taken together, our findings uncovered that the HF potentiated anti-inflammatory effect in DSS-induced colitis in mice and its underlying mechanisms could be associated with the inhibition of HIF-1α and reduced levels of acylcarnitines, suggesting that both the inhibition of HIF-1α and the counteraction of incomplete FAO might be useful in the prevention and treatment of inflammatory bowel disease.

  6. Anti-inflammatory mechanism of oxymatrine in dextran sulfate sodium-induced colitis of rats

    Institute of Scientific and Technical Information of China (English)

    Ping Zheng; Feng-Li Niu; Wen-Zhong Liu; Yao Shi; Lun-Gen Lu

    2005-01-01

    AIM: To investigate the anti-inflammatory mechanism of oxymatrine in dextran sulfate sodium (DSS)-induced colitis of rats.METHODS: Acute colitis was induced by giving 2% DSS orally in drinking water for 8 d. Twenty-six male rats were randomized into oxymatrine-treated group (group A, 10rats), DSS control (group B, 10 rats) and normal control (group C, 6 rats). The rats in group A were injected from d 1 to 11 and drank 2% DSS solution from d 4 to 11.The rats in group B were treated with 0.9% saline in an equal volume as group A and drank 2% DSS solution from d 4 to 11. The rats in group C were treated with 0.9% saline as group B from d 1 to 11 and drank water normally. Diarrhea and bloody stool as well as colonic histology were observed. The levels of serum tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were determined by ELISA, and nuclear factor-κB (NF-κB)activity and the expression of inter-cellular adhesion molecule-1 (ICAM-1) in colonic mucosa were detected by immunohistochernistry method.RESULTS: Compared with DSS control group, the inflammatory symptoms and histological damages of colonic mucosa in oxymatrine-treated group were significantly improved, the serum levels of TNF-α, IL-6, and the expression of NF-κB, ICAM-1 in colonic mucosa were significantly reduced.CONCLUSION: The fact that oxymatrine can reduce the serum levels of TNF-α, IL-6, and the expression of NF-κB and ICAM-1 in colonic mucosa in DSS-induced colitis of rats indicates that oxymatrine may ameliorate the colonic inflammation and thus alleviate diarrhea and bloody stool.

  7. Dextran sulfate sodium-induced colitis-associated neoplasia: a promising model for the development of chemopreventive interventions

    Institute of Scientific and Technical Information of China (English)

    Margie Lee CLAPPER; Harry Stanley COOPER; Wen-Chi Lee CHANG

    2007-01-01

    Individuals diagnosed with ulcerative colitis face a significantly increased risk of developing colorectal dysplasia and cancer during their lifetime. To date, little attention has been given to the development of a chemopreventive intervention for this high-risk population. The mouse model of dextran sulfate sodium (DSS) -induced colitis represents an excellent preclinical system in which to both charac-terize the molecular events required for tumor formation in the presence of inflam-marion and assess the ability of select agents to inhibit this process. Cyclic admin-istration of DSS in drinking water results in the establishment of chronic colitis and the development of colorectal dysplasias and cancers with pathological fea-tures that resemble those of human colitis-associated neoplasia. The incidence and multiplicity of lesions observed varies depending on the mouse strain used (ie, Swiss Webster, C57BL/6J, CBA, ICR) and the dose (0.7%-5.0%) and schedule (1-15 cycles with or without a subsequent recovery period) of DSS. The incidence of neoplasia can be increased and its progression to invasive cancer accelerated significantly by administering DSS in combination with a known colon carcinogen(azoxymethane (AOM), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)) or iron. More recent induction of colitis-associated neoplasia in genetically defined mouse strains has provided new insight into the role of specific genes (ie, adenomatous polyposis coli (Apc),p53, inducible nitric oxide synthase (iNOS), Msh2) in the development of colitis-associated neoplasias. Emerging data from chemopreventive intervention studies document the efficacy of several agents in inhibiting DSS-induced neoplasia and provide great promise that colitis-associated colorectal neoplasia is a pre-ventable disease.

  8. A Central Role for Induced Regulatory T Cells in Tolerance Induction in Experimental Colitis1

    OpenAIRE

    Haribhai, Dipica; Lin, Wen; Edwards, Brandon; Ziegelbauer, Jennifer; Salzman, Nita H.; Carlson, Marc R.; Li, Shun-Hwa; Simpson, Pippa M.; Chatila, Talal A; Williams, Calvin B.

    2009-01-01

    In addition to thymus-derived or natural T regulatory (nTreg) cells, a second subset of induced T regulatory (iTreg) cells arises de novo from conventional CD4+ T cells in the periphery. The function of iTreg cells in tolerance was examined in a CD45RBhighCD4+ T cell transfer model of colitis. In situ-generated iTreg cells were similar to nTreg cells in their capacity to suppress T cell proliferation in vitro and their absence in vivo accelerated bowel disease. Treatment with nTreg cells reso...

  9. Expression of interleukin 6 in brain and colon of rats with TNBS-induced colitis

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM:To characterise expression of interleukin 6(IL-6),a potent proinflammatory cytokine,in the occurrence and development of inflammatory bowel disease(IBD) and investigate its effect on neuroimmunomodulation and immune homeostasis regulation.METHODS:In this study,rats with colitis induced by trinitrobenzene sulfonic acid(TNBS) were sacrificed on days 3,7,14,21 and 28 after induction.In the controls,the TNBS was just replaced by equivalent amount of phosphate buffered solution(PBS,0.01 mol/L).IL-6 mRNA expr...

  10. Processed coffee alleviates DSS-induced colitis in mice

    OpenAIRE

    Fiebich, Bernd L.; Amaya G. Vinuesa; Gonzalo Sanchez-Duffhues; Juan A. Collado; Thorsten Rose; Jörn Menthe; Eduardo Muñoz

    2013-01-01

    ABSTRACTBackground: Coffee is one of the most widely consumed beverages in the world and it has been demonstrated that it has important therapeutic activities not only because of its caffeine content but also owing to the presence of other biologically active small molecules such as chlorogenic acid, trigonelline and cyclopentadiones. However, chlorogenic acid is degraded into catechol, pyrogallol and hydroxyhydroquinone, which are thought to induce irritation of the gastric mucosa. To reduce...

  11. Chemerin aggravates DSS-induced colitis by suppressing M2 macrophage polarization.

    Science.gov (United States)

    Lin, Yuli; Yang, Xuguang; Yue, Wenjie; Xu, Xiaofei; Li, Bingji; Zou, Linlin; He, Rui

    2014-07-01

    Chemerin is present in various inflammatory sites and is closely involved in tissue inflammation. Recent studies have demonstrated that chemerin treatment can cause either anti-inflammatory or pro-inflammatory effects according to the disease model being investigated. Elevated circulating chemerin was recently found in patients with inflammatory bowel disease (IBD); however, the role of chemerin in intestinal inflammation remains unknown. In this study, we demonstrated that the administration of exogenous chemerin (aa17-156) aggravated the severity of dextran sulfate sodium (DSS)-induced colitis, which was characterized by higher clinical scores, extensive mucosal damage and significantly increased local and systemic production of pro-inflammatory cytokines, including IL-6, TNF-α and interferon (IFN-γ). Interestingly, chemerin did not appear to influence the magnitudes of inflammatory infiltrates in the colons, but did result in significantly decreased colonic expression of M2 macrophage-associated genes, including Arginase 1 (Arg-1), Ym1, FIZZ1 and IL-10, following DSS exposure, suggesting an impaired M2 macrophage skewing in vivo. Furthermore, an in vitro experiment showed that the addition of chemerin directly suppressed M2 macrophage-associated gene expression and STAT6 phosphorylation in IL-4-stimulated macrophages. Significantly elevated chemerin levels were found in colons from DSS-exposed mice and from ulcerative colitis (UC) patients and appeared to positively correlate with disease severity. Moreover, the in vivo administration of neutralizing anti-chemerin antibody significantly improved intestinal inflammation following DSS exposure. Taken together, our findings reveal a pro-inflammatory role for chemerin in DSS-induced colitis and the ability of chemerin to suppress the anti-inflammatory M2 macrophage response. Our study also suggests that upregulated chemerin in inflamed colons may contribute to the pathogenesis of IBD.

  12. Therapeutic and prophylactic thalidomide in TNBS-induced colitis: Synergistic effects on TNF-α, IL-12 and VEGF production

    Institute of Scientific and Technical Information of China (English)

    Ana Teresa Carvalho; Cláudio Tortori; Ilana Dines; Jane Carvalho; Eduardo Rocha; Celeste Elia; Heitor Souza; Antonio Jose Carneiro; Morgana Castelo-Branco; Kalil Madi; Alberto Schanaider; Flavia Silva; Fernando Antonio Pereira Jú'nior; Márcia G Pereira

    2007-01-01

    AIM: To evaluated the therapeutic and prophylactic effect of thalidomide on 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-induced colitis. Thalidomide has been reported to downregulate the expression of tumor necrosis factor α (TNF-α), IL-12, and vascular endothelial growth factor (VEGF), hallmarks of intestinal inflammation in Crohn's disease (CD).METHODS: Male Wistar rats were divided in five groups of ten animals each. Four groups received a rectal infusion of TNBS in ethanol. The first group was sacrificed 7 d after colitis induction. The second and third groups received either thalidomide or placebo by gavage and were sacrificed at 14 d. The fourth group received thalidomide 6 h before TNBS administration, and was sacrificed 7 d after induction. The fifth group acted as the control group and colitis was not induced. Histological inflammatory scores of the colon were performed and lamina propria CD4+ T cells, macrophages, and VEGF+ cells were detected by immunohistochemistry. TNF-α and IL-12 were quantified in the supernatant of organ cultures by ELISA.RESULTS: Significant reduction in the inflammatory score and in the percentage of VEGF+ cells was observed in the group treated with thalidomide compared with animals not treated with thalidomide. Both TNF-α and IL-12 levels were significantly reduced among TNBS induced colitis animals treated with thalidomide compared with animals that did not receive thalidomide.TNF-α levels were also significantly reduced among the animals receiving thalidomide prophylaxis compared with untreated animals with TNBS-induced colitis. Intestinal levels of TNF-α and IL-12 were significantly correlated with the inflammatory score and the number of VEGF+ cells.CONCLUSION: Thalidomide significantly attenuates TNBS-induced colitis by inhibiting the intestinal production of TNF-α, IL-12, and VEGF. This effect may support the use of thalidomide as an alternate approach in selected patients with CD.

  13. Loss of n-6 fatty acid induced pediatric obesity protects against acute murine colitis

    Science.gov (United States)

    Dietary influences may affect microbiome composition and host immune responses, thereby modulating propensity toward inflammatory bowel diseases: Crohn disease and ulcerative colitis. Dietary n-6 fatty acids have been associated with ulcetative colitis in prospective studies. However, the critical d...

  14. β7-Integrin exacerbates experimental DSS-induced colitis in mice by directing inflammatory monocytes into the colon.

    Science.gov (United States)

    Schippers, A; Muschaweck, M; Clahsen, T; Tautorat, S; Grieb, L; Tenbrock, K; Gaßler, N; Wagner, N

    2016-03-01

    Leukocyte recruitment is pivotal for the initiation and perpetuation of inflammatory bowel disease (IBD) and controlled by the specificity and interactions of chemokines and adhesion molecules. Interactions of the adhesion molecules α4β7-integrin and mucosal addressin cell-adhesion molecule-1 (MAdCAM-1) promote the accumulation of pathogenic T-cell populations in the inflamed intestine. We aimed to elucidate the significance of β7-integrin expression on innate immune cells for the pathogenesis of IBD. We demonstrate that β7-integrin deficiency protects recombination-activating gene-2 (RAG-2)-deficient mice from dextran sodium sulfate (DSS)-induced colitis and coincides with decreased numbers of colonic effector monocytes. We also show that β7-integrin is expressed on most CD11b(+)CD64(low)Ly6C(+) bone marrow progenitors and contributes to colonic recruitment of these proinflammatory monocytes. Importantly, adoptive transfer of CD115(+) wild-type (WT) monocytes partially restored the susceptibility of RAG-2/β7-integrin double-deficient mice to DSS-induced colitis, thereby demonstrating the functional importance of β7-integrin-expressing monocytes for the development of DSS colitis. We also reveal that genetic ablation of MAdCAM-1 ameliorates experimental colitis in RAG-2-deficient mice as well. In summary, we demonstrate a previously unknown role of α4β7-integrin-MAdCAM-1 interactions as drivers of colitis by directing inflammatory monocytes into the colon.

  15. Tanshinone IIA Protects against Dextran Sulfate Sodium- (DSS-) Induced Colitis in Mice by Modulation of Neutrophil Infiltration and Activation.

    Science.gov (United States)

    Liu, Xiaowei; He, Haiyue; Huang, Tingting; Lei, Zhen; Liu, Fuquan; An, Guangyu; Wen, Tao

    2016-01-01

    Neutrophils play a critical role in the initiation and maintenance of intestinal inflammation. However, conventional neutrophil-targeted therapies can impair normal host defense. Tanshinone IIA has been recently revealed to act directly on neutrophils. Hence, we aimed at investigating whether Tanshinone IIA can protect against experimental colitis through modulation of neutrophils. We induced colitis in C57BL/6 mice by giving 3% dextran sulfate sodium (DSS) orally, and meanwhile, we treated mice daily with Tanshinone IIA intraperitoneally. The severity of colitis was evaluated by calculating disease activity index (DAI) and histological parameters. Neutrophil infiltration and activation in the colons of mice were measured. Moreover, whether Tanshinone IIA has direct effects on neutrophil migration and activation was determined in vitro. Our data showed that Tanshinone IIA significantly ameliorated the severity of DSS-induced colitis in mice, evidenced by the reduced DAI and improved colonic inflammation. In addition, Tanshinone IIA decreased neutrophil infiltration of intestinal mucosa and activation and reduced colonic inflammatory cytokines in DSS-treated mice. Furthermore, Tanshinone IIA was demonstrated to significantly suppress neutrophil migration and activation. These results provide compelling evidence that Tanshinone IIA has a therapeutic potential for alleviating inflammatory colitis in mice, which is possibly mediated by the immunomodulation of neutrophils.

  16. Impact of dextran sulphate sodium-induced colitis on the intestinal transport of the colon carcinogen PhIP.

    Science.gov (United States)

    Nicken, Petra; von Keutz, Anne; Willenberg, Ina; Ostermann, Annika I; Schebb, Nils Helge; Giovannini, Samoa; Kershaw, Olivia; Breves, Gerhard; Steinberg, Pablo

    2016-05-01

    Colorectal cancer is one of the most frequent cancers in Western countries. Chronic intestinal diseases such as Crohn's disease and ulcerative colitis, in which the intestinal barrier is massively disturbed, significantly raise the risk of developing a colorectal tumour. 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a genotoxic heterocyclic aromatic amine that is formed after strongly heating fish and meat. In this study, the hypothesis that PhIP uptake in the gut is increased during chronic colitis was tested. Chronic colitis was induced by oral administration of dextran sulphate sodium (DSS) to Fischer 344 rats. The transport of PhIP in eight different rat intestinal segments was examined in Ussing chambers. The tissues were incubated with 10 µM PhIP for 90 min, and the concentration of PhIP was determined in the mucosal and serosal compartments of the Ussing chambers as well as in the clamped tissues by LC-MS. Although chronic colitis was clearly induced in the rats, no differences in the intestinal transport of PhIP were observed between control and DSS-treated animals. The hypothesis that in the course of chronic colitis more PhIP is taken up by the intestinal epithelium, thereby increasing the risk of developing colorectal cancer, could not be confirmed in the present report. PMID:26070365

  17. Lactobacillus casei prevents the development of dextran sulphate sodium-induced colitis in Toll-like receptor 4 mutant mice.

    Science.gov (United States)

    Chung, Y W; Choi, J H; Oh, T-Y; Eun, C S; Han, D S

    2008-01-01

    Probiotics, defined as live or attenuated bacteria or bacterial products, confer a significant health benefit to the host. Recently, they have been shown to be useful in the treatment of chronic inflammatory bowel disease and infectious colitis. In this study, we investigated the effect of probiotics on the development of experimental colitis using Toll-like receptor 4 (TLR-4) mutant (lps-/lps-) mice. TLR-4(lps-/lps-) and wild-type (WT) mice were given 2.5% dextran sulphate sodium (DSS) in drinking water to induce colitis with or without Lactobacillus casei pretreatment. Clinical and histological activity of DSS-colitis was attenuated markedly both in TLR-4(lps-/lps-) and WT mice pretreated with L. casei. Interestingly, histological activity was less severe in TLR-4(lps-/lps-) mice than in WT mice. The levels of myeloperoxidase activity and interleukin (IL)-12p40 were attenuated in pretreated TLR-4(lps-/lps-) mice after DSS administration. By contrast, transforming growth factor (TGF)-beta and IL-10 mRNA and protein expressions were increased markedly in pretreated TLR-4(lps-/lps-) mice. The current results suggest that L. casei has a preventive effect in the development of acute DSS-induced colitis and its action depends largely upon TLR-4 status. L. casei modulates the expression of inflammatory cytokines and down-regulates neutrophilic infiltration in the case of incomplete TLR-4 complex signalling. PMID:18005362

  18. Changes of CD8+ T cells in dextran sulfate sodium-induced colitis mice pretreated with oral immune regulation

    Institute of Scientific and Technical Information of China (English)

    YE Yue-fang; JIN Xi; CHEN Shao-hua; YUE Min; LI You-ming

    2012-01-01

    Background It has been reported that CD8+ regulatory cells could be induced upon oral tolerance.The purpose of this study was to investigate the changes of CD8α+ T cells in dextran sulfate sodium (DSS)-induced colitis mice pretreated by oral immune regulation.Methods The effects of five low oral doses of colitis-extracted proteins (CEP) on colitis were evaluated by clinical manifestation and histological lesions.The percentages of CD8α+ T ceils gating on CD3+ T cells were evaluated in the gut-associated lymphoid tissues (GALT) and the spleens by flow cytometry.Differences between the two groups were compared by Student's t test or Mann-Whitney U test.Results Compared to bovine serum albumin (BSA)-fed control mice,administration of CEP resulted in marked alleviation of colitis.The proportion of CD8α+ T cells,not only in intraepithelial lymphocytes (IELs) and lamina propria lymphocytes (LPLs) of the large intestine (LI) but also in spleen from CEP-fed colitis mice,was significantly higher than that from BSA-fed colitis mice (LI-IELs:(71.5±5.4)% vs.(60.1±4.3)%,P <0.01; LI-LPLs:(60.7±5.2)% vs.(51.9±4.7)%,P<0.01; spleen:(24.1±3.6)% vs.(20.3±4.1)%,P <0.05; n=8).Mucosal repair in repair-period mice five days after termination of DSS treatment was also accompanied by an increase of CD8α+ T cells in large intestinal mucosal lymphocytes (LI-IELs:(72.1±3.7)% vs.(61.5±4.5)%,P <0.01; LI-LPLs:(62.1±5.7)% vs.(52.7±3.6)%,P <0.01; n=8).The proportion of CD3+ T cells increased in Peyer's patches (PPs) and decreased in mesenteric lymph nodes (MLNs) from colitis mice compared to untreated mice,whereas the change pattern of CD3+T cells in PPs and MLNs from CEP-fed colitis mice was just on the contrary.Conclusion Improvement of DSS-induced colitis resulted from oral immune regulation is associated with an increase in CD8α+ T cells in spleen and large intestinal mucosa.

  19. Interferon-γ induces expression of MHC class II on intestinal epithelial cells and protects mice from colitis.

    Directory of Open Access Journals (Sweden)

    Christoph Thelemann

    Full Text Available Immune responses against intestinal microbiota contribute to the pathogenesis of inflammatory bowel diseases (IBD and involve CD4(+ T cells, which are activated by major histocompatibility complex class II (MHCII molecules on antigen-presenting cells (APCs. However, it is largely unexplored how inflammation-induced MHCII expression by intestinal epithelial cells (IEC affects CD4(+ T cell-mediated immunity or tolerance induction in vivo. Here, we investigated how epithelial MHCII expression is induced and how a deficiency in inducible epithelial MHCII expression alters susceptibility to colitis and the outcome of colon-specific immune responses. Colitis was induced in mice that lacked inducible expression of MHCII molecules on all nonhematopoietic cells, or specifically on IECs, by continuous infection with Helicobacter hepaticus and administration of interleukin (IL-10 receptor-blocking antibodies (anti-IL10R mAb. To assess the role of interferon (IFN-γ in inducing epithelial MHCII expression, the T cell adoptive transfer model of colitis was used. Abrogation of MHCII expression by nonhematopoietic cells or IECs induces colitis associated with increased colonic frequencies of innate immune cells and expression of proinflammatory cytokines. CD4(+ T-helper type (Th1 cells - but not group 3 innate lymphoid cells (ILCs or Th17 cells - are elevated, resulting in an unfavourably altered ratio between CD4(+ T cells and forkhead box P3 (FoxP3(+ regulatory T (Treg cells. IFN-γ produced mainly by CD4(+ T cells is required to upregulate MHCII expression by IECs. These results suggest that, in addition to its proinflammatory roles, IFN-γ exerts a critical anti-inflammatory function in the intestine which protects against colitis by inducing MHCII expression on IECs. This may explain the failure of anti-IFN-γ treatment to induce remission in IBD patients, despite the association of elevated IFN-γ and IBD.

  20. Safety and efficacy of Profermin(R) to induce remission in ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Aleksander Krag; Hans Israelsen; Bjφrn von Ryberg; Klaus K Andersen; Flemming Bendtsen

    2012-01-01

    AIM:To test the efficacy and safety of Profermin(R) in inducing remission in patients with active ulcerative colitis (UC).METHODS:The study included 39 patients with mild to moderate UC defined as a Simple Clinical Colitis Activity Index (SCCAI) > 4 and < 12 (median:7.5),who were treated open-label with Profermin(R) twice daily for 24 wk.Daily SCCAI was reported observer blinded via the Internet.RESULTS:In an intention to treat (ITT) analysis,the mean reduction in SCCAI score was 56.5%.Of the 39 patients,24 (62%) reached the primary endpoint,which was proportion of patients with ≮ 50% reduction in SCCAI.Our secondary endpoint,the proportion of patients in remission defined as SCCAI ≤ 2.5,was in ITT analysis reached in 18 of the 39 patients (46%).In a repeated-measure regression analysis,the estimated mean reduction in score was 5.0 points (95% CI:4.1-5.9,P < 0.001) and the estimated mean time taken to obtain half the reduction in score was 28 d (95% CI:26-30).There were no serious adverse events (AEs) or withdrawals due to AEs.Profermin(R)was generally well tolerated.CONCLUSION:Profermin(R) is safe and may be effective in inducing remission of active UC.

  1. Curative effects of sodium fusidate on the development of dinitrobenzenesulfonic acid-induced colitis in rats

    DEFF Research Database (Denmark)

    Di Marco, Roberto; Mangano, Katia; Quattrocchi, Cinzia;

    2003-01-01

    Fusidic acid and sodium fusidate (fusidin) are antibiotics with low toxicity and powerful immunomodulatory activities in vitro and in vivo. In this study we have evaluated the effect of fusidin on the development of dinitrobenzenesulfonic acid (DNB)-induced colitis in rats that serves as a precli......Fusidic acid and sodium fusidate (fusidin) are antibiotics with low toxicity and powerful immunomodulatory activities in vitro and in vivo. In this study we have evaluated the effect of fusidin on the development of dinitrobenzenesulfonic acid (DNB)-induced colitis in rats that serves...... as a preclinical model of human inflammatory bowel disease (IBD). The data show that when administered orally at the dose of 80 (but not 40) mg/kg body wt under a "therapeutic" regimen soon after DNB application, fusidin significantly ameliorates clinical, histological, and seroimmunological signs of disease......-gamma compared with untreated controls. The present findings concur with the beneficial actions of fusidin in a pilot study conducted in patients with Crohn's disease and warrant controlled studies in humans with IBD....

  2. Enhanced mucosal re-epithelialization induced by short chain fatty acids in experimental colitis

    Directory of Open Access Journals (Sweden)

    Aguilar-Nascimento J.E.

    1999-01-01

    Full Text Available The short chain fatty acids (SCFA are the best nutrients for the colonocytes. Glucose is poorly used as a fuel but may be transformed into SCFA by colonic bacteria. The aim of this study was to investigate the effect of SCFA or glucose on experimental colitis. Colitis was induced in 30 Wistar rats by colonic instillation of 4% acetic acid. Five days later they were randomized to receive twice a day colonic lavage containing saline (controls, N = 10, 10% hypertonic glucose (N = 10 or SCFA (N = 10 until day 8 when they were killed. At autopsy, the colon was removed and weighed and the mucosa was evaluated macro- and microscopically and stripped out for DNA assay. Data are reported as mean ± SD or median [range] as appropriate. All animals lost weight but there was no difference between groups. Colon weight was significantly lower in the SCFA group (3.8 ± 0.5 g than in the control (5.3 ± 2.1 g and glucose (5.2 ± 1.3 g groups (P<0.05. Macroscopically, the severity of inflammation was less in SCFA (grade 2 [1-5] than in control (grade 9 [4-10] and glucose-treated (grade 9 [2-10] animals (P<0.01. Microscopically, ulceration of the mucosa was more severe in the glucose and control groups than in the SCFA group. The DNA content of the mucosa of SCFA-treated animals (8.2 [5.0-20.2] mg/g of tissue was higher than in glucose-treated (5.1 [4.2-8.5] mg/g of tissue; P<0.01 and control (6.2 [4.5-8.9] mg/g of tissue; P<0.05 animals. We conclude that SCFA may enhance mucosal re-epithelialization in experimental colitis, whereas hypertonic glucose is of no benefit.

  3. Cytosolic phospholipase A2 α has a crucial role in the pathogenesis of DSS-induced colitis in mice.

    Science.gov (United States)

    Rosengarten, Marina; Hadad, Nurit; Solomonov, Yulia; Lamprecht, Sergio; Levy, Rachel

    2016-02-01

    Colitis, an inflammation of the colon, is a well-characterized massive tissue injury. Cytosolic phospholipase A2 α (cPLA2 α) upregulation plays an important role in the development of several inflammatory diseases. The aim of the present study was to define the role of cPLA2 α upregulation in the development of colitis. We used a mouse model of dextran sulfate sodium induced colitis. Immunoblotting analysis showed that cPLA2 α and NF-κB were upregulated and activated in the colon from day 2 of colitis induction. This molecular event preceded the development of the disease, as determined by Disease Activity Index score, body weight, colon length, and the expression of colonic inflammatory markers, including neutrophil infiltration detected by myeloperoxidase and by NIMP-R14, ICAM-1, COX-2, iNOS upregulation and LTB4 and TNF-α secretion. Prevention of cPLA2 α upregulation and activity in the colon by i.v. administration of specific antisense oligonucleotides against cPLA2 α 1 day prior and every day of exposure to dextran sulfate sodium significantly impeded the development of the disease and prevented NF-κB activation, neutrophils infiltration into the colonic mucosa, and expression of proinflammatory proteins in the colon. Our results demonstrate a critical role of cPLA2 α upregulation in inflammation and development of murine colitis.

  4. Alpinetin attenuates inflammatory responses by suppressing TLR4 and NLRP3 signaling pathways in DSS-induced acute colitis.

    Science.gov (United States)

    He, Xuexiu; Wei, Zhengkai; Wang, Jingjing; Kou, Jinhua; Liu, Weijian; Fu, Yunhe; Yang, Zhengtao

    2016-06-20

    Alpinetin, a composition of Alpinia katsumadai Hayata, has been reported to have a number of biological properties, such as antibacterial, antitumor and other important therapeutic activities. However, the effect of alpinetin on inflammatory bowel disease (IBD) has not yet been reported. The purpose of this study was to investigate the anti-inflammatory effect and mechanism of alpinetin on dextran sulfate sodium (DSS)-induced colitis in mice. In vivo, DSS-induced mice colitis model was established by giving mice drinking water containing 5% (w/v) DSS for 7 days. Alpinetin (25, 50 and 100 mg/kg) were administered once a day by intraperitoneal injection 3 days before DSS treatment. In vitro, phorbol myristate acetate (PMA)-differentiated monocytic THP-1 macrophages were treated with alpinetin and stimulated by lipopolysaccharide (LPS). The results showed that alpinetin significantly attenuated diarrhea, colonic shortening, histological injury, myeloperoxidase (MPO) activity and the expressions of tumor necrosis factor (TNF-α) and interleukin (IL-1β) production in mice. In vitro, alpinetin markedly inhibited LPS-induced TNF-α and IL-1β production, as well as Toll-like receptor 4 (TLR4) mediated nuclear transcription factor-kappaB (NF-κB) and NOD-like receptor protein 3 (NLRP3) inflammasome activation. In conclusion, this study demonstrated that alpinetin had protective effects on DSS-induced colitis and may be a promising therapeutic reagent for colitis treatment.

  5. IL-33 Aggravates DSS-Induced Acute Colitis in Mouse Colon Lamina Propria by Enhancing Th2 Cell Responses.

    Science.gov (United States)

    Zhu, Junfeng; Yang, Fangli; Sang, Lixuan; Zhai, Jingbo; Zhang, Xiaoqing; Yue, Dan; Li, Shengjun; Li, Yan; Lu, Changlong; Sun, Xun

    2015-01-01

    Interleukin- (IL-) 33, a member of the IL-1 cytokine family, is an important modulator of the immune system associated with several immune-mediated diseases. IL-33 was expressed in high level on epithelial cells of intestinal tract. It suggested that IL-33 plays a potential role in inflammatory bowel diseases (IBD). We investigated the role of interleukin- (IL-) 33 in dextran sulphate sodium- (DSS-) induced acute colitis in mice using recombinant mouse IL-33 protein (rIL-33). We found that DSS-induced acute colitis was aggravated by rIL-33 treatment. rIL-33-treated DSS mice showed markedly reduced levels of interferon- (IFN-)γ and IL-17A in their colon lamina propria lymphocytes (LPL), but the levels of Th2 cytokines, such as IL-5 and IL-13, in these cells were significantly increased, compared to DSS mice treated with PBS. Our results suggested that IL-33 stimulated CD4(+)T cells and caused the cell to adopt a Th2-type response but at the same time suppressed Th17 and Th1 cell responses. Therefore, IL-33 may be involved in pathogenesis of DSS-induced acute colitis by promoting Th2 cell response in intestinal mucosa of mice. Modulation of IL-33/ST2 signaling by monoclonal antibody (mAb) could be a novel biological therapy in DSS-induced acute colitis.

  6. Increased visceral sensitivity to capsaicin after DSS-induced colitis in mice : spinal cord c-Fos expression and behavior

    NARCIS (Netherlands)

    Eijkelkamp, Niels; Kavelaars, Annemieke; Elsenbruch, Sigrid; Schedlowski, Manfred; Holtmann, Gerald; Heijnen, Cobi J.

    2007-01-01

    Increased visceral sensitivity to capsaicin after DSS-induced colitis in mice: spinal cord c-Fos expression and behavior. Am J Physiol Gastrointest Liver Physiol 293: G749-G757, 2007. First published July 26, 2007; doi:10.1152/ajpgi.00114.2007.During acute and chronic inflammation visceral pain perc

  7. Genetic deletion of IL-25 (IL-17E) confers resistance to dextran sulfate sodium-induced colitis in mice

    Science.gov (United States)

    IL-25 is emerging as a key regulator of inflammation in the intestinal mucosa because of its ability to promote Th2 while suppressing Th1 and Th17 cytokine responses. We investigated the contribution of endogenous IL-25 to DSS-induced colitis in mice. Mice were exposed to DSS in drinking water ad li...

  8. Immunological mechanisms involved in probiotic-mediated protection against Citrobacter rodentium-induced colitis.

    Science.gov (United States)

    Jiang, Y; Yang, G; Meng, F; Yang, W; Hu, J; Ye, L; Shi, C; Wang, C

    2016-06-01

    Inflammatory bowel disease is a group of chronic, incurable inflammatory disorders of the gastrointestinal tract that cause severe diarrhoea, intestinal inflammation, pain, fatigue and weight loss. In this study, we first developed a model of Citrobacter rodentium-induced colitis and then evaluated the protective effects of selected probiotics on inflammation. The results showed that administration of a combination of probiotics including Lactobacillus rhamnosus ATCC 53103, Lactobacillus acidophilus ATCC 4356 and Lactobacillus plantarum A significantly increased the production of CD11c(+) dendritic cells in the spleen (3.62% vs phosphate buffered saline (PBS)-treated control, P<0.01) and mesenteric lymph nodes (MLNs). In addition, the presence of probiotics significantly up-regulated the development of CD4(+)/CD25(+)/Foxp3(+) regulatory T cells in MLNs by approximately 2.07% compared to the effect observed in the PBS-treated control (P<0.01) and down-regulated the expression of inflammatory cytokines, including interleukin-17, tumour necrosis factor-α and interferon-γ, by 0.11, 0.11 and 0.15%, respectively, compared to the effect observed in the PBS-treated control (P<0.01).These effects conferred protection against colitis, as shown by histopathological analyses.

  9. Immunological mechanisms involved in probiotic-mediated protection against Citrobacter rodentium-induced colitis.

    Science.gov (United States)

    Jiang, Y; Yang, G; Meng, F; Yang, W; Hu, J; Ye, L; Shi, C; Wang, C

    2016-06-01

    Inflammatory bowel disease is a group of chronic, incurable inflammatory disorders of the gastrointestinal tract that cause severe diarrhoea, intestinal inflammation, pain, fatigue and weight loss. In this study, we first developed a model of Citrobacter rodentium-induced colitis and then evaluated the protective effects of selected probiotics on inflammation. The results showed that administration of a combination of probiotics including Lactobacillus rhamnosus ATCC 53103, Lactobacillus acidophilus ATCC 4356 and Lactobacillus plantarum A significantly increased the production of CD11c(+) dendritic cells in the spleen (3.62% vs phosphate buffered saline (PBS)-treated control, Pprobiotics significantly up-regulated the development of CD4(+)/CD25(+)/Foxp3(+) regulatory T cells in MLNs by approximately 2.07% compared to the effect observed in the PBS-treated control (P<0.01) and down-regulated the expression of inflammatory cytokines, including interleukin-17, tumour necrosis factor-α and interferon-γ, by 0.11, 0.11 and 0.15%, respectively, compared to the effect observed in the PBS-treated control (P<0.01).These effects conferred protection against colitis, as shown by histopathological analyses. PMID:26925601

  10. Protective effect of the methanolic extract of malva parviflora l. leaves on acetic acid-induced ulcerative colitis in rats

    Directory of Open Access Journals (Sweden)

    Aisha Dugani

    2016-01-01

    Full Text Available Background/Aims: Inflammatory bowel disease (IBD is a general term describing chronic, idiopathic relapsing, inflammatory conditions of the gastrointestinal tract of unknown etiology. Previous studies have indicated that Malva parviflora leaf extract possesses anti-inflammatory, antioxidant, and antiulcerogenic activity. activity. This work aimed to investigatee the anti-inflammatory effect of the methanolic (MEMP and aqueous (AEMP extracts of M. parviflora leaves on acetic acid-induced colitis in rats. Materials and Methods: 42 male Wistar albino rats were divided into seven groups (n = 6. Group I: Normal saline control group with no colitis; Group II: Acetic acid colitis group; Group III: 100 mg/kg/5 d MEMP; Group IV: 200 mg/kg/5 d.MEMP; Group V: 100 mg/kg/5 d AEMP; Group VI: 200 mg/kg/5 d AEMP; Group VII: Prednisolone group (2 mg/kg/5 d. Treatments were followed by induction of colitis using intrarectal instillation of 2 mL of 4% acetic acid. Colon damage was evaluated macroscopically (spleen weight/body weight, colon weight/length ratio and the histological changes were also recorded. Results: The results of this study showed that acetic acid caused severe inflammation of the colon and a significant increase in spleen weight/body weight, and an increase in colon weight/length ratio compared with normal control group. Pretreatment with MEMP and AEMP for 5 days followed by induction of colitis resulted in a significant attenuation of spleen weight and colon weight/length ratio compared with acetic acid control group. Methanolic extract provided better anticolitic effect than aqueous extract; the effect was prominent at the dose of 200 mg/kg. Histopathological findings confirmed the protective effect of the MEMP. Conclusion: In conclusion, MEMP could ameliorate mucosal damage in experimentally induced colitis when given orally.

  11. IL-10/microRNA-155/SHIP-1 signaling pathway is crucial for commensal bacteria induced spontaneous colitis.

    Science.gov (United States)

    Li, Yi; Tian, Yun; Zhu, Weiming; Gong, Jianfeng; Guo, Zhen; Guo, Feilong; Gu, Lili; Li, Jieshou

    2016-09-15

    Interleukin 10 (IL-10) microRNA-155 (miR-155)/Src homology 2 domain-containing inositol 5-phosphatase 1 (SHIP-1) signaling pathway plays an important role in maintaining immune homeostasis. We aimed to determine and characterize the changes induced by commensal bacteria on the IL-10/miR-155/SHIP-1 signaling pathway, as well as the potential therapeutic effects of anti-miR-155 on colitis in IL-10 deficient (IL-10(-)/(-)) mice. Age- and sex-matched C57BL/6 IL-10(-)/(-) and wild type mice were transferred from a germ-free environment to a specific pathogen free condition. Part of IL-10(-)/(-) mice were then treated with anti-miR-155. IL-10/miR-155/SHIP-1 signaling pathway was evaluated and the therapeutic effects of anti-miR-155 treatment on colitis in IL-10(-)/(-) mice was assessed. The expression and the relationship of IL-10, miR-155, and SHIP-1 were also measured in patients with active Crohn's colitis. IL-10/miR-155/SHIP-1 signaling pathway was activated in IL-10(-)/(-) mice transferring from a germ-free environment to a specific pathogen free condition. Anti-miR-155 treatment significantly ameliorated the severity of colitis in IL-10(-)/(-) mice. Additionally, administration of anti-miR-155 was associated with a restoration of SHIP-1 signaling pathway. The relationship of IL-10, miR-155, and SHIP-1 was confirmed in human study using samples from patients with active Crohn's colitis. IL-10/miR-155/SHIP-1 pathways play a critical role in commensal bacteria induced colitis and miR-155 may be a potential therapeutic target for human inflammatory bowel disease. PMID:27395764

  12. Propionate Ameliorates Dextran Sodium Sulfate-Induced Colitis by Improving Intestinal Barrier Function and Reducing Inflammation and Oxidative Stress.

    Science.gov (United States)

    Tong, Ling-Chang; Wang, Yue; Wang, Zhi-Bin; Liu, Wei-Ye; Sun, Sheng; Li, Ling; Su, Ding-Feng; Zhang, Li-Chao

    2016-01-01

    Propionate is a short chain fatty acid that is abundant as butyrate in the gut and blood. However, propionate has not been studied as extensively as butyrate in the treatment of colitis. The present study was to investigate the effects of sodium propionate on intestinal barrier function, inflammation and oxidative stress in dextran sulfate sodium (DSS)-induced colitis mice. Animals in DSS group received drinking water from 1 to 6 days and DSS [3% (w/v) dissolved in double distilled water] instead of drinking water from 7 to 14 days. Animals in DSS+propionate (DSS+Prop) group were given 1% sodium propionate for 14 consecutive days and supplemented with 3% DSS solution on day 7-14. Intestinal barrier function, proinflammatory factors, oxidative stress, and signal transducer and activator of transcription 3 (STAT3) signaling pathway in the colon were determined. It was found that sodium propionate ameliorated body weight loss, colon-length shortening and colonic damage in colitis mice. Sodium propionate significantly inhibited the increase of FITC-dextran in serum and the decrease of zonula occludens-1 (ZO-1), occludin, and E-cadherin expression in the colonic tissue. It also inhibited the expression of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) mRNA and phosphorylation of STAT3 in colitis mice markedly, reduced the myeloperoxidase (MPO) level, and increased the superoxide dismutase and catalase level in colon and serum compared with DSS group. Sodium propionate inhibited macrophages with CD68 marker infiltration into the colonic mucosa of colitis mice. These results suggest that oral administration of sodium propionate could ameliorate DSS-induced colitis mainly by improving intestinal barrier function and reducing inflammation and oxidative stress via the STAT3 signaling pathway. PMID:27574508

  13. UNC5B receptor deletion exacerbates DSS-induced colitis in mice by increasing epithelial cell apoptosis.

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    Ranganathan, Punithavathi; Jayakumar, Calpurnia; Li, Dean Y; Ramesh, Ganesan

    2014-07-01

    The netrin-1 administration or overexpression is known to protect colon from acute colitis. However, the receptor that mediates netrin-1 protective activities in the colon during colitis remains unknown. We tested the hypothesis that UNC5B receptor is a critical mediator of protective function of netrin-1 in dextran sodium sulfate (DSS)-induced colitis using mice with partial deletion of UNC5B receptor. DSS colitis was performed in mice with partial genetic UNC5B deficiency (UNC5B(+/-) mice) or wild-type mice to examine the role of endogenous UNC5B. These studies were supported by in vitro models of DSS-induced apoptosis in human colon epithelial cells. WT mice developed colitis in response to DSS feeding as indicated by reduction in bw, reduction in colon length and increase in colon weight. These changes were exacerbated in heterozygous UNC5B knockout mice treated with DSS. Periodic Acid-Schiff stained section shows damages in colon epithelium and mononuclear cell infiltration in WT mice, which was further increased in UNC5B heterozygous knockout mice. This was associated with large increase in inflammatory mediators such as cytokine and chemokine expression and extensive apoptosis of epithelial cells in heterozygous knockout mice as compared to WT mice. Overexpression of UNC5B human colon epithelial cells suppressed DSS-induced apoptosis and caspase-3 activity. Moreover, DSS induced large amount of netrin-1 and shRNA mediated knockdown of netrin-1 induction exacerbated DSS-induced epithelial cell apoptosis. Our results suggest that UNC5B is a critical mediator of cell survival in response to stress in colon.

  14. Inhibition of Aloperine on Dextran Sulphate Sodium-induced Chronic Colitis in C57BL/6 Mice

    Institute of Scientific and Technical Information of China (English)

    SONG Li-jun; ZHAO Wen-chang; DENG Hong-zhu

    2012-01-01

    Objective To investigate the effects of aloperine (ALO) on a model of dextran sulphate sodium (DSS)-induced chronic colitis in C57BL/6 mice.Methods Repeated colitis was induced by administration of four cycles of 4% DSS.The severity of colitis was assessed on the basis of clinical signs,ratio of colon weight and colon length,and histological grading scores.Moreover,secretory immunoglobulin A (S-IgA) and plasma haptoglobin (HP) were analyzed by enzyme-linked immunosorbent assay,and the changes of mRNA expression of ICAM-1and MIF gene in colorectal tissue were detected by quantitative reverse transcriptase real-time polymerase chain reaction using SYBR Green Ⅰ.Results ALO administration significantly attenuated the colon damage,caused substantial reductions of the rise in HP,and maintained the level of cecum S-IgA.ALO inhibited the ICAM-1mRNA expression and had no effect on MIF mRNA expression.Conclusion The effect of ALO on DSS-induced chronic colitis in mice is investigated for the first time,which suggests that ALO could be an attractive therapeutic candidate in the treatment of inflammatory bowel disease.

  15. Perilla frutescens extract ameliorates DSS-induced colitis by suppressing proinflammatory cytokines and inducing anti-inflammatory cytokines.

    Science.gov (United States)

    Urushima, Hayato; Nishimura, Junichi; Mizushima, Tsunekazu; Hayashi, Noriyuki; Maeda, Kazuhisa; Ito, Toshinori

    2015-01-01

    Anti-inflammatory effects have been reported in Perilla frutescens leaf extract (PE), which is a plant of the genus belonging to the Lamiaceae family. We examined the effect of PE on dextran sulfate sodium (DSS)-induced colitis. Preliminarily, PE was safely administered for 7 wk without any adverse effects. In the preventive protocol, mice were fed 1.5% DSS solution dissolved in distilled water (control group) or 0.54% PE solution (PE group) ad libitum for 7 days. In the therapeutic protocol, distilled water or 0.54% PE solution was given for 10 days just after administration of 1.5% DSS for 5 days. PE intake significantly improved body weight loss. The serum cytokine profile demonstrated that TNF-α, IL-17A, and IL-10 were significantly lower in the PE group than in the control group. In the therapeutic protocol, mice in the PE group showed significantly higher body weight and lower histological colitis scores compared with mice in the control group on day 15. The serum cytokine profile demonstrated that TGF-β was significantly higher in the PE group than in the control group. In distal colon mRNA expression, TNF-α, and IL-17A were significantly downregulated. In vitro analyses of biologically active ingredients, such as luteolin, apigenin, and rosmarinic acid, in PE were performed. Luteolin suppressed production of proinflammatory cytokines, such as TNF-α, IL-1β, IL-6, and IL-17A. Apigenin also suppressed secretion of IL-17A and increased the anti-inflammatory cytokine IL-10. Rosmarinic acid increased the regulatory T cell population. We conclude that PE might be useful in treatment and prevention of DSS-induced colitis.

  16. Perilla frutescens extract ameliorates DSS-induced colitis by suppressing proinflammatory cytokines and inducing anti-inflammatory cytokines.

    Science.gov (United States)

    Urushima, Hayato; Nishimura, Junichi; Mizushima, Tsunekazu; Hayashi, Noriyuki; Maeda, Kazuhisa; Ito, Toshinori

    2015-01-01

    Anti-inflammatory effects have been reported in Perilla frutescens leaf extract (PE), which is a plant of the genus belonging to the Lamiaceae family. We examined the effect of PE on dextran sulfate sodium (DSS)-induced colitis. Preliminarily, PE was safely administered for 7 wk without any adverse effects. In the preventive protocol, mice were fed 1.5% DSS solution dissolved in distilled water (control group) or 0.54% PE solution (PE group) ad libitum for 7 days. In the therapeutic protocol, distilled water or 0.54% PE solution was given for 10 days just after administration of 1.5% DSS for 5 days. PE intake significantly improved body weight loss. The serum cytokine profile demonstrated that TNF-α, IL-17A, and IL-10 were significantly lower in the PE group than in the control group. In the therapeutic protocol, mice in the PE group showed significantly higher body weight and lower histological colitis scores compared with mice in the control group on day 15. The serum cytokine profile demonstrated that TGF-β was significantly higher in the PE group than in the control group. In distal colon mRNA expression, TNF-α, and IL-17A were significantly downregulated. In vitro analyses of biologically active ingredients, such as luteolin, apigenin, and rosmarinic acid, in PE were performed. Luteolin suppressed production of proinflammatory cytokines, such as TNF-α, IL-1β, IL-6, and IL-17A. Apigenin also suppressed secretion of IL-17A and increased the anti-inflammatory cytokine IL-10. Rosmarinic acid increased the regulatory T cell population. We conclude that PE might be useful in treatment and prevention of DSS-induced colitis. PMID:25359539

  17. Protective role of G-CSF in dextran sulfate sodium-induced acute colitis through generating gut-homing macrophages.

    Science.gov (United States)

    Meshkibaf, Shahab; Martins, Andrew J; Henry, Garth T; Kim, Sung Ouk

    2016-02-01

    Granulocyte colony-stimulating factor (G-CSF) is a pleiotropic cytokine best known for its role in promoting the generation and function of neutrophils. G-CSF is also found to be involved in macrophage generation and immune regulation; however, its in vivo role in immune homeostasis is largely unknown. Here, we examined the role of G-CSF in dextran sulfate sodium (DSS)-induced acute colitis using G-CSF receptor-deficient (G-CSFR(-/-)) mice. Mice were administered with 1.5% DSS in drinking water for 5days, and the severity of colitis was measured for the next 5days. GCSFR(-/-) mice were more susceptible to DSS-induced colitis than G-CSFR(+/+) or G-CSFR(-/+) mice. G-CSFR(-/-) mice harbored less F4/80(+) macrophages, but a similar number of neutrophils, in the intestine. In vitro, bone marrow-derived macrophages prepared in the presence of both G-CSF and macrophage colony-stimulating factor (M-CSF) (G-BMDM) expressed higher levels of regulatory macrophage markers such as programmed death ligand 2 (PDL2), CD71 and CD206, but not in arginase I, transforming growth factor (TGF)-β, Ym1 (chitinase-like 3) and FIZZ1 (found in inflammatory zone 1), and lower levels of inducible nitric oxide synthase (iNOS), CD80 and CD86 than bone marrow-derived macrophages prepared in the presence of M-CSF alone (BMDM), in response to interleukin (IL)-4/IL-13 and lipopolysaccharide (LPS)/interferon (IFN)-γ, respectively. Adoptive transfer of G-BMDM, but not BMDM, protected G-CSFR(-/-) mice from DSS-induced colitis, and suppressed expression of tumor necrosis factor (TNF)-α, IL-1β and iNOS in the intestine. These results suggest that G-CSF plays an important role in preventing colitis, likely through populating immune regulatory macrophages in the intestine.

  18. Very long O-antigen chains enhance fitness during Salmonella-induced colitis by increasing bile resistance.

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    Robert W Crawford

    2012-09-01

    Full Text Available Intestinal inflammation changes the luminal habitat for microbes through mechanisms that have not been fully resolved. We noticed that the FepE regulator of very long O-antigen chain assembly in the enteric pathogen Salmonella enterica serotype Typhimurium (S. Typhimurium conferred a luminal fitness advantage in the mouse colitis model. However, a fepE mutant was not defective for survival in tissue, resistance to complement or resistance to polymyxin B. We performed metabolite profiling to identify changes in the luminal habitat that accompany S. Typhimurium-induced colitis. This analysis suggested that S. Typhimurium-induced colitis increased the luminal concentrations of total bile acids. A mutation in fepE significantly reduced the minimal inhibitory concentration (MIC of S. Typhimurium for bile acids in vitro. Oral administration of the bile acid sequestrant cholestyramine resin lowered the concentrations of total bile acids in colon contents during S. Typhimurium infection and significantly reduced the luminal fitness advantage conferred by the fepE gene in the mouse colitis model. Collectively, these data suggested that very long O-antigen chains function in bile acid resistance of S. Typhimurium, a property conferring a fitness advantage during luminal growth in the inflamed intestine.

  19. Huangqin-Tang Ameliorates TNBS-Induced Colitis by Regulating Effector and Regulatory CD4+ T Cells

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    Ying Zou

    2015-01-01

    Full Text Available Huangqin-Tang decoction (HQT is a classic traditional Chinese herbal formulation that is widely used to ameliorate the symptoms of gastrointestinal disorders, including inflammatory bowel disease (IBD. This study was designed to investigate the therapeutic potential and immunological regulatory activity of HQT in experimental colitis in rats. Using an animal model of colitis by intrarectally administering 2,4,6-trinitrobenzenesulfonic acid (TNBS, we found that administration of HQT significantly inhibited the severity of TNBS-induced colitis in a dose-dependent manner. In addition, treatment with HQT produced better results than that with mesalazine, as shown by improvedweight loss bleeding and diarrhoea scores, colon length, and intestinal inflammation. As for potential immunological regulation of HQT action, the percentages of Th1 and Th17 cells were reduced, but those Th2 and Treg cells were enhanced in LPMCs after HQT treatment. Additionally, HQT lowered the levels of Th1/Th17-associated cytokines but increased production of Th2/Treg-associated cytokines in the colon and MLNs. Furthermore, we observed a remarkable suppression of the Th1/Th17-associated transcription factors T-bet and ROR-γt. However, expression levels of the Th2/Treg-associated transcription factors GATA-3 and Foxp3 were enhanced during treatment with HQT. Our results suggest that HQT has the therapeutic potential to ameliorate TNBS-induced colitis symptoms. This protective effect is possibly mediated by its effects on CD4+ T cells subsets.

  20. Interleukin-6 induces S100A9 expression in colonic epithelial cells through STAT3 activation in experimental ulcerative colitis.

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    Min Jeoung Lee

    Full Text Available BACKGROUND: Intestinal epithelium is essential for maintaining normal intestinal homeostasis; its breakdown leads to chronic inflammatory pathologies, such as inflammatory bowel diseases (IBDs. Although high concentrations of S100A9 protein and interleukin-6 (IL-6 are found in patients with IBD, the expression mechanism of S100A9 in colonic epithelial cells (CECs remains elusive. We investigated the role of IL-6 in S100A9 expression in CECs using a colitis model. METHODS: IL-6 and S100A9 expression, signal transducer and activator of transcription 3 (STAT3 phosphorylation, and infiltration of immune cells were analyzed in mice with dextran sulfate sodium (DSS-induced colitis. The effects of soluble gp130-Fc protein (sgp130Fc and S100A9 small interfering (si RNA (si-S100A9 on DSS-induced colitis were evaluated. The molecular mechanism of S100A9 expression was investigated in an IL-6-treated Caco-2 cell line using chromatin immunoprecipitation assays. RESULTS: IL-6 concentrations increased significantly in the colon tissues of DSS-treated mice. sgp130Fc or si-S100A9 administration to DSS-treated mice reduced granulocyte infiltration in CECs and induced the down-regulation of S100A9 and colitis disease activity. Treatment with STAT3 inhibitors upon IL-6 stimulation in the Caco-2 cell line demonstrated that IL-6 mediated S100A9 expression through STAT3 activation. Moreover, we found that phospho-STAT3 binds directly to the S100A9 promoter. S100A9 may recruit immune cells into inflamed colon tissues. CONCLUSIONS: Elevated S100A9 expression in CECs mediated by an IL-6/STAT3 signaling cascade may play an important role in the development of colitis.

  1. Prevention of tri-nitrobenzene of sulfonic acid-induced colitis in chicken by using extract of Aloe vera

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    Motamed Elsayed Mahmoud

    Full Text Available Aim: Aloe vera, species of succulent plant in the genus Aloe, has multiple clinical activities and used routinely to accelerate wound healing. The present study was designed to investigate the anti-inflammatory effect of Aloe vera extracts (AVE in vitro and in vivo. Materials and Methods: The effect of crude AVE on inducible nitric oxide production by LPS/IFNg-stimulated cultured macrophages was evaluated. The therapeutic effect of administering crude Aloe vera extracts (100 mg/kg b.w. on the development of tri-nitrobenzene of sulfonic acid (TNBS-induced colitis (40 mg/kg b. w. in chicken was also investigated. Chicken is a valuable model for this purpose because it showed preference to bitter taste of Aloe vera. Diverse clinical pictures of the colitis including weight loss, diarrhea and histopathological changes were evaluated. Results: Nitrite production by LPS/IFNg-stimulated macrophages was maximally reduced by adding of AVE (100 μg/ml. This result suggests a direct inhibitory effect of AVE on the inflammatory cells. Chicks treated orally with AVE showed improvement of the histological signs with no inflammatory cell infiltrates and reduction of myeloperoxidase (MPO activities when compared with colitis control group. AVE pretreatment ameliorated significantly the clinical and histopathological severity of the TNBS-induced colitis; decreased body weight loss and diarrhea and increased survival. Conclusion: It was concluded that oral administration of AVE represents a valuable therapeutic approach for the treatment of colitis in chicken. [Vet. World 2012; 5(8.000: 469-476

  2. Autophagy deficiency in myeloid cells increases susceptibility to obesity-induced diabetes and experimental colitis.

    Science.gov (United States)

    Lee, Hae-Youn; Kim, Jinyoung; Quan, Wenying; Lee, June-Chul; Kim, Min-Soo; Kim, Seok-Hyung; Bae, Jin-Woo; Hur, Kyu Yeon; Lee, Myung-Shik

    2016-08-01

    Autophagy, which is critical for the proper turnover of organelles such as endoplasmic reticulum and mitochondria, affects diverse aspects of metabolism, and its dysregulation has been incriminated in various metabolic disorders. However, the role of autophagy of myeloid cells in adipose tissue inflammation and type 2 diabetes has not been addressed. We produced mice with myeloid cell-specific deletion of Atg7 (autophagy-related 7), an essential autophagy gene (Atg7 conditional knockout [cKO] mice). While Atg7 cKO mice were metabolically indistinguishable from control mice, they developed diabetes when bred to ob/w mice (Atg7 cKO-ob/ob mice), accompanied by increases in the crown-like structure, inflammatory cytokine expression and inflammasome activation in adipose tissue. Mφs (macrophages) from Atg7 cKO mice showed significantly higher interleukin 1 β release and inflammasome activation in response to a palmitic acid plus lipopolysaccharide combination. Moreover, a decrease in the NAD(+):NADH ratio and increase in intracellular ROS content after treatment with palmitic acid in combination with lipopolysaccharide were more pronounced in Mφs from Atg7 cKO mice, suggesting that mitochondrial dysfunction in autophagy-deficient Mφs leads to an increase in lipid-induced inflammasome and metabolic deterioration in Atg7 cKO-ob/ob mice. Atg7 cKO mice were more susceptible to experimental colitis, accompanied by increased colonic cytokine expression, T helper 1 skewing and systemic bacterial invasion. These results suggest that autophagy of Mφs is important for the control of inflammasome activation in response to metabolic or extrinsic stress, and autophagy deficiency in Mφs may contribute to the progression of metabolic syndrome associated with lipid injury and colitis. PMID:27337687

  3. Healing Effect of PistaciaAtlantica Fruit Oil Extract in Acetic Acid-Induced Colitis in Rats

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    Nader Tanideh

    2014-11-01

    Full Text Available Background: Considering the anti-oxidant properties of Pistaciaatlanticaand lack of data regarding its efficacy in the treatment of ulcerative colitis, this study aims at investigating the effect of the Pistaciaatlantica fruit extract in treating experimentally induced colitis in a rat model. Methods:Seventy male Sprague-Dawley rats (weighing 220±20 g were used. All rats fasted 24 hours before the experimental procedure. The rats were randomly divided into 7 groups, each containing 10 induced colitis with 2ml acetic acid (3%. Group 1 (Asacol, group 2 (base gel and group 7 (without treatment were assigned as control groups. Group 3 (300 mg/ml and group 4 (600 mg/ml received Pistaciaatlantica fruit orally. Group 5 (10% gel and group 6 (20% gel received Pistaciaatlantica in the form of gel as enema. Macroscopic, histopathological examination and MDA measurement were carried out. Results:All groups revealed significant macroscopic healing in comparison with group 7 (P<0.001. Regarding microscopic findings in the treatment groups compared with group 7, the latter group differed significantly with groups 1, 2, 4 and 6 (P<0.001. There was a significant statistical difference in MDA scores of the seven treatment groups (F(5,54=76.61, P<0.001. Post-hoc comparisons indicated that the mean±SD score of Asacol treated group (1.57±0.045 was not significantly different from groups 4 (1.62±0.024 and 6 (1.58±0.028. Conclusion: Our study showed that a high dose of Pistaciaatlantica fruit oil extract, administered orally and rectally can improve colitis physiologically and pathologically in a rat model, and may be efficient for ulcerative colitis.

  4. A study of the effects of Cydonia oblonga Miller (Quince) on TNBS-induced ulcerative colitis in rats.

    Science.gov (United States)

    Minaiyan, M; Ghannadi, A; Etemad, M; Mahzouni, P

    2012-04-01

    Cydonia oblonga Miller (Quince) from Rosaceae family is a fruit tree cultivated in many countries mainly in Iran. This study was carried out to investigate the effect of quince juice (QJ) and quince hydroalcoholic extract (QHE) on ulcerative colitis (UC) induced by TNBS (trinitrobenzene sulfonic acid) in rats. Rats were grouped (n=6) and fasted for 36 h before colitis induction. TNBS was instilled into the colon with a hydroalcoholic carrier and then treatments were made for 5 days starting 6 h after colitis induction with different doses of QJ (200, 400, 800 mg/kg), QHE (200, 500 & 800 mg/kg) orally, QJ (400 mg/kg) and QHE (200 and 500 mg/kg) intraperitoneally. The colon tissue was removed and tissue damages were scored after macroscopic and histopathologic assessments. Albeit the examined doses of QJ and QHE were apparently effective to reduce the extent of UC lesions, only the greatest doses (500 and 800 mg/kg) resulted in significant alleviation. Weight/Length ratio as an illustrative of tissue inflammation and extravasation was also diminished with quince treatments while the results correlated with macroscopic and histopathologic evaluations. These data suggest that QJ and QHE were effective to diminish inflammation and ulcer indices in this murine model of acute colitis. Although QHE with different doses was effective in induced colitis, the dose and/or route of administration dependency was not confirmed. So quince fractions could be considered as a suitable anticolitic alternative, however further studies are needed to support this hypothesis for clinical setting. PMID:23181087

  5. Effect of acute and chronic DSS induced colitis on plasma eicosanoid and oxylipin levels in the rat.

    Science.gov (United States)

    Willenberg, Ina; Ostermann, Annika I; Giovannini, Samoa; Kershaw, Olivia; von Keutz, Anne; Steinberg, Pablo; Schebb, Nils Helge

    2015-07-01

    Eicosanoids and oxylipins are potent lipid mediators involved in the regulation of inflammation. In order to evaluate their role and suitability as biomarkers in colitis, we analyzed their systemic levels in the acute and chronic phase of dextran sulfate sodium (DSS) induced colitis. Male Fischer 344 rats were treated in three cycles with 4% DSS in the drinking water (4 days followed by 10 days recovery) and blood was drawn 3 days prior to the first DSS treatment and on days 4, 11, 32 and 39. Histopathological evaluation of the colon tissue after 42 days showed that the animals developed a mild to severe chronic colitis. Consistently, prostaglandin levels were massively (twofold) elevated in the colonic tissue. LC-MS based targeted metabolomics was used to determine plasma oxylipin levels at the different time points. In the acute phase of inflammation directly after DSS treatment, epoxy-fatty acid (FA), dihydroxy-FA and hydroxy-FA plasma concentrations were uniformly elevated. With each treatment cycle the increase in these oxylipin levels was more pronounced. Our data suggest that in the acute phase of colitis release of polyunsaturated FAs from membranes in the inflamed tissue is reflected by a uniform increase of oylipins formed in different branches of the arachidonic acid cascade. However, during the recovery phases the systemic oxylipin pattern is not or only moderately altered and does not allow to evaluate the onset of chronic inflammation in the colon.

  6. Anti-inflammatory effect of Prunus armeniaca L. (Apricot) extracts ameliorates TNBS-induced ulcerative colitis in rats.

    Science.gov (United States)

    Minaiyan, M; Ghannadi, A; Asadi, M; Etemad, M; Mahzouni, P

    2014-01-01

    Prunus armeniaca L. (Apricot) is a tree cultivated in different parts of the world. Apricot kernel as a good dietary supplement has shown antioxidant, anti-inflammatory and other pharmacologic properties which suggest that it may be functional as an anticolitis agent. In this study we evaluated the effects of apricot kernel extract and oil on ulcerative colitis in rats. Rats were fasted for 36 h before the experiment. Colitis was induced by intra-rectal instillation of 50 mg/kg trinitrobenzene sulfonic acid in male Wistar rats. Treatments were started 6 h after colitis induction and continued every 24 h for 5 days. Apricot kernel extract (100, 200, 400 mg/kg p.o. and 100, 400 mg/kg i.p.) and apricot kernel extract/oil (100, 200, 400 mg/kg p.o.) were used as experimental treatments and prednisolone (4 mg/kg p.o. or i.p.) was used as reference drug. On the day 6, colon tissue was removed and macroscopic and pathologic parameters were evaluated. Ulcer index and total colitis index as representative of macroscopic and histologic parameters respectively showed ameliorating effects in experimental groups especially those treated by intraperitoneal administration route. Results also demonstrated that oil fraction was not able to potentiate the effects of extract. These data suggest that apricot kernel extracts (with or without oil) can be introduced for further mechanistic and clinical studies as a complementary medicine for inflammatory bowel disorders. PMID:25657793

  7. Critical appraisal of the current practice in murine TNBS-induced colitis

    NARCIS (Netherlands)

    A.A.T. Velde; M.I. Verstege; D.W. Hommes

    2006-01-01

    There is no standard practice in the induction of colitis by 2,4,6-trinitrobenzene sulfonic acid. In this review the current practice in 2,4,6-trinitrobenzene sulfonic acid colitis is studied using 20 recently published articles. We compare the different protocols, discuss the mechanism of disease a

  8. Ameliorative effects of bombesin and neurotensin on trinitrobenzene sulphonic acid-induced colitis, oxidative damage and apoptosis in rats

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    AIM: To investigate the effects of bombesin (BBS) and neurotensin (NTS) on apoptosis and colitis in an ulcerative colitis model. METHODS: In this study, a total of 50 rats were divided equally into 5 groups. In the control group, no colitis induction or drug administration was performed. Colitis was induced in all other groups. Following the induction of colitis, BBS, NTS or both were applied to three groups of rats. The remaining group (colitis group) received no treatment. On the 11th d after induction of colitis and drug treatment, blood samples were collected for TNF-α and IL-6 level studies. Malondialdehyde (MDA), carbonyl, myeloperoxidase (MPO) and caspase-3 activities, as well as histopathological findings, evaluated in colonic tissues. RESULTS: According to the macroscopic and microscopic findings, the study groups treated with BBS,NTS and BBS+NTS showed significantly lower damage and inflammation compared with the colitis group (macroscopic score,2.1±0.87,3.7±0.94 and 2.1±0.87 vs 7.3 ± 0.94; microscopic score,2.0 ±0.66,3.3±0.82 and 1.8±0.63 vs 5.2±0.78,P<0.01=.TNF-αand IL-6 levels were increased significantly in all groups compared with the control group. These increases were significantly smaller in the BBS,NTS and BBS+NTS groups compared with the colitis group (TNF-α levels,169.69±53.56,245.86±64.85 and 175.54 4±42.19vs 556.44±49.82; IL-6 levels,443.30±53.99,612.80±70.39 and 396.80±78.43 vs 1505.90±222.23,P<0.05=.The colonic MPO and MDA levels were significantly lower in control, BBS, NTS and BBS+NTS groups than in the colitis group (MPO levels,24.36±8.10,40.51±8.67 and 25.83±6.43 vs 161.47±38.24; MDA levels,4.70±1.41,6.55±1.12 and 4.51±0.54 vs15.60±1.88,P<0.05=.Carbonyl content and caspase-3 levels were higher in the colitis and NTS groups than in control, BBS and BBS+NTS groups (carbonyl levels,553.99±59.58and 336.26±35.72 vs 209.76±30.92,219.76±25.77and 220.34 36.95; caspase-3 levels,451.70±68.27and 216.20

  9. Protective Effect of Calculus Bovis Sativus on Dextran Sulphate Sodium-Induced Ulcerative Colitis in Mice

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    Xiping Li

    2015-01-01

    Full Text Available Calculus Bovis Sativus (CBS is a commonly used traditional Chinese medicine, which has been reported to exhibit antispasmodic, fever-reducing, anti-inflammatory, and gallbladder-repairing effects. The present study aims to investigate the protective effect of CBS on dextran sulphate sodium- (DSS- induced ulcerative colitis (UC in mice. C57BL/6 male mice were exposed to 5% DSS in drinking water. CBS was given orally at 50 and 150 mg/kg once per day for 7 days. Body weight, disease activity index (DAI, colon length, colonic myeloperoxidase (MPO activity, superoxide dismutase (SOD activity, and malondialdehyde (MDA and nitric oxide (NO levels were measured. Administration of CBS significantly reserved these changes, decreased the MPO activity and MDA and NO level, and increased the SOD activity in the colon tissue. Histological observation suggested that CBS alleviated edema, mucosal damage, and inflammatory cells infiltration induced by DSS in the colon. Moreover, CBS significantly downregulated the mRNA expression of tumor necrosis factor-α (TNF-α, interleukin- (IL- 1β and IL-6 in the colon tissue. Our data suggested that CBS exerted protective effect on DSS-induced UC partially through the antioxidant and anti-inflammatory activities.

  10. Protective Effect of Calculus Bovis Sativus on Dextran Sulphate Sodium-Induced Ulcerative Colitis in Mice.

    Science.gov (United States)

    Li, Xiping; Xu, Yanjiao; Zhang, Chengliang; Deng, Li; Chang, Mujun; Yu, Zaoqin; Liu, Dong

    2015-01-01

    Calculus Bovis Sativus (CBS) is a commonly used traditional Chinese medicine, which has been reported to exhibit antispasmodic, fever-reducing, anti-inflammatory, and gallbladder-repairing effects. The present study aims to investigate the protective effect of CBS on dextran sulphate sodium- (DSS-) induced ulcerative colitis (UC) in mice. C57BL/6 male mice were exposed to 5% DSS in drinking water. CBS was given orally at 50 and 150 mg/kg once per day for 7 days. Body weight, disease activity index (DAI), colon length, colonic myeloperoxidase (MPO) activity, superoxide dismutase (SOD) activity, and malondialdehyde (MDA) and nitric oxide (NO) levels were measured. Administration of CBS significantly reserved these changes, decreased the MPO activity and MDA and NO level, and increased the SOD activity in the colon tissue. Histological observation suggested that CBS alleviated edema, mucosal damage, and inflammatory cells infiltration induced by DSS in the colon. Moreover, CBS significantly downregulated the mRNA expression of tumor necrosis factor-α (TNF-α), interleukin- (IL-) 1β and IL-6 in the colon tissue. Our data suggested that CBS exerted protective effect on DSS-induced UC partially through the antioxidant and anti-inflammatory activities. PMID:26579201

  11. Anti-inflammatory effect of Moringa oleifera Lam. seeds on acetic acid-induced acute colitis in rats

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    Mohsen Minaiyan

    2014-02-01

    Full Text Available Objective: Anti-inflammatory, immuno-modulatory, and antioxidant properties of Moringa oleifera Lam. suggest that it might have beneficial effects on colitis. The present study was performed to investigate the anticolitis effect of Moringa oleifera seeds hydro-alcoholic extract (MSHE and its chloroform fraction (MCF on acetic acid-induced colitis in rats. Materials and Methods: Both MSHE and MCF with three increasing doses (50, 100, and 200 mg/kg were administered orally to separate groups of male Wistar rats, 2 h before ulcer induction (using acetic acid 4% and continued for 5 days. Prednisolone (4 mg/kg and normal saline (1 ml/kg were used in reference and control groups, respectively. All rats were sacrificed 24 h after the last dose (at day 6 and tissue injuries were assessed macroscopically and pathologically. Results: Extracts with three doses mentioned before were effective to reduce weight of distal colon (8 cm as a marker for inflammation and tissue edema. Three doses of MSHE and two greater doses of MCF (100 and 200 mg/kg were effective to reduce ulcer severity, area, and index as well as mucosal inflammation severity and extent, crypt damage, invasion involvement, total colitis index, and MPO activity compared with controls. MCF (50 mg/kg was not significantly effective in reducing evaluated parameters of colitis compared with controls. Conclusion: It is concluded that MSHE and MCF were both effective to treat experimental colitis and this might be attributed to their similar major components, biophenols and flavonoids. Since the efficacy was evident even in low doses of MSHE, presence of active constituents with high potency in seeds is persuasive.

  12. Cerebral venous thrombosis and heparin-induced thrombocytopenia in an 18-year old male with severe ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Gudrun Scheving Thorsteinsson; Maria Magnussson; Lena M Hallberg; Nils Gunnar Wahlgren; Fredrik Lindgren; Petter Malmborg; Thomas H Casswall

    2008-01-01

    The risk of thromboembolism is increased in inflammatory bowel disease and its symptoms may be overlooked. Furthermore, its treatment can be complex and is not without complications. We describe a case of an adolescent boy who developed a cerebral sinus venous thrombosis during a relapse of his ulcerative colitis and who, while on treatment with heparin,developed heparin-induced thrombocytopenia (HIT).The treatment was then switched to fondaparinux, a synthetic and selective inhibitor of activated factor x.

  13. Comparative Study of Berberis vulgaris Fruit Extract and Berberine Chloride Effects on Acetic Acid-Induced Colitis in Rats

    OpenAIRE

    Minaiyan, Mohsen; Ghannadi, Alireza; Mahzouni, Parvin; Jaffari-Shirazi, Elham

    2011-01-01

    Antioxidant and immunomodulatory effects of anthocyanins are abundant in berberry fruits suggesting that they may have beneficial effects on inflammatory bowel diseases (IBD). The present study was carried out to investigate the anti-colitic effect of Berberis vulgaris fruit extract (BFE) compared to berberine chloride (BEC) and corticosteroids using an animal model of acetic acid induced experimental colitis. BFE with three different doses (375, 750, and 1500 mg/Kg) was administered orally o...

  14. Does radiation prevent 5-fluorouracil-induced colitis in the early phase of radiochemotherapy? A case report and literature review

    International Nuclear Information System (INIS)

    Case Report: A 43-year-old man with T3 N2 M0 adenocarcinoma of the lower rectum was admitted for preoperative radiochemotherapy (RCT). Daily fractions of 1.8 Gy (planned total dose: 50.4 Gy) and concomitant chemotherapy consisting of 5-fluorouracil (5-FU), leucovorin, and mitomycin C (MMC) were administered. On day 10, the patient developed abdominal pain and massive diarrhea. Computed tomography, endoscopy, histopathologic and serologic tests revealed severe colitis confined to the upper abdomen and most probably related to 5-FU. Unexpectedly, the bowel inflammation was restricted to areas not irradiated. 4 months later, during the course of disease, relapse with pulmonary metastases occurred. A palliative chemotherapy with 5-FU, oxaliplatin, and leucovorin was started. Again, the patient suffered from severe diarrhea and dose reduction was necessary. Discussion: It was speculated that in the early phase of RCT the well-known anti-inflammatory nature of low-dose radiation prevented exacerbation of colitis. To the authors' knowledge, this observation has not been published before. With respect to the current literature and the clinical findings it is discussed that both increased leukocyte/endothelial cell adhesion and altered release of reactive oxygen species or inducible nitric oxide synthase (iNOS) may play a role in 5-FU-induced colitis. Conclusion: This observation led to the hypothesis that the anti-inflammatory effect of low-dose irradiation may attenuate 5-FU-induced colitis in the very early phase of RCT. It appears worthwhile to separate side effects of RCT into radiation- and chemotherapy-induced effects, which requires a detailed diagnostic work-up. This differentiation has an impact on planning individual therapy: the authors did not saw conclusive evidence of an increased radiosensitivity but chemosensitivity in their patient and therefore continued radiotherapy. This assumption was confirmed when the patient received palliative 5-FU

  15. Does radiation prevent 5-fluorouracil-induced colitis in the early phase of radiochemotherapy? A case report and literature review

    Energy Technology Data Exchange (ETDEWEB)

    Rischke, H.C.; Momm, F.; Henke, M.; Frommhold, H. [University Hospital Freiburg (Germany). Dept. of Radiotherapy; Wiech, T. [University Hospital Freiburg (Germany). Dept. of General Pathology and Pathologic Anatomy

    2007-08-15

    Case Report: A 43-year-old man with T3 N2 M0 adenocarcinoma of the lower rectum was admitted for preoperative radiochemotherapy (RCT). Daily fractions of 1.8 Gy (planned total dose: 50.4 Gy) and concomitant chemotherapy consisting of 5-fluorouracil (5-FU), leucovorin, and mitomycin C (MMC) were administered. On day 10, the patient developed abdominal pain and massive diarrhea. Computed tomography, endoscopy, histopathologic and serologic tests revealed severe colitis confined to the upper abdomen and most probably related to 5-FU. Unexpectedly, the bowel inflammation was restricted to areas not irradiated. 4 months later, during the course of disease, relapse with pulmonary metastases occurred. A palliative chemotherapy with 5-FU, oxaliplatin, and leucovorin was started. Again, the patient suffered from severe diarrhea and dose reduction was necessary. Discussion: It was speculated that in the early phase of RCT the well-known anti-inflammatory nature of low-dose radiation prevented exacerbation of colitis. To the authors' knowledge, this observation has not been published before. With respect to the current literature and the clinical findings it is discussed that both increased leukocyte/endothelial cell adhesion and altered release of reactive oxygen species or inducible nitric oxide synthase (iNOS) may play a role in 5-FU-induced colitis. Conclusion: This observation led to the hypothesis that the anti-inflammatory effect of low-dose irradiation may attenuate 5-FU-induced colitis in the very early phase of RCT. It appears worthwhile to separate side effects of RCT into radiation- and chemotherapy-induced effects, which requires a detailed diagnostic work-up. This differentiation has an impact on planning individual therapy: the authors did not saw conclusive evidence of an increased radiosensitivity but chemosensitivity in their patient and therefore continued radiotherapy. This assumption was confirmed when the patient received palliative 5-FU

  16. Effects of natural raw meal (NRM) on high-fat diet and dextran sulfate sodium (DSS)-induced ulcerative colitis in C57BL/6J mice

    OpenAIRE

    Shin, Sung-Ho; Song, Jia-Le; Park, Myoung-Gyu; Park, Mi-Hyun; Hwang, Sung-Joo; Park, Kun-Young

    2015-01-01

    BACKGROUND/OBJECTIVES Colitis is a serious health problem, and chronic obesity is associated with the progression of colitis. The aim of this study was to determine the effects of natural raw meal (NRM) on high-fat diet (HFD, 45%) and dextran sulfate sodium (DSS, 2% w/v)-induced colitis in C57BL/6J mice. MATERIALS/METHODS Body weight, colon length, and colon weight-to-length ratio, were measured directly. Serum levels of obesity-related biomarkers, triglyceride (TG), total cholesterol (TC), l...

  17. Norisoboldine ameliorates DSS-induced ulcerative colitis in mice through induction of regulatory T cells in colons.

    Science.gov (United States)

    Lv, Qi; Qiao, Si-miao; Xia, Ying; Shi, Can; Xia, Yu-feng; Chou, Gui-xin; Wang, Zheng-tao; Dai, Yue; Wei, Zhi-feng

    2015-12-01

    Norisoboldine (NOR), the main active constituent of Radix Linderae, was previously demonstrated to ameliorate collagen-induced arthritis in rats through regulating the imbalance of T cells in intestines, which implied its therapeutic potential in inflammatory bowel disease. Here, we investigated the effect of NOR on ulcerative colitis (UC) induced by dextran sulfate sodium (DSS) in mice. Results showed that NOR (20, 40mg/kg) markedly reduced the symptoms of colitis, the levels of IL-1β and TNF-α, and the activation of ERK, p38 MAPK and NF-κB-p65. NOR only slightly decreased the levels of IFN-γ and IL-17A in mouse colons, but it dramatically increased the level of IL-10 at both protein and mRNA grades. Consistently, NOR increased the number of CD4(+)CD25(+)Foxp3(+) Treg cells more obviously than it decreased that of CD4(+)IL-17(+) Th17 cells in mesenteric lymph nodes (MLNs) and colonic lamina proprias (LPs) of colitis mice, and promoted the expression of Foxp3 mRNA in colon tissues. It could facilitate the in vitro differentiation of Treg cells from naive T cells and promote the phosphorylations of Smad2/3 in colon tissues of colitis mice. On the other hand, NOR did not affect the expressions of homing receptors CCR9 and α4β7 in SPs, and homing ligands CCL25 and Madcam-1 in MLNs and colonic LPs, suggesting that the increase of Treg cells in colons by NOR was not due to gut homing. In conclusion, NOR can ameliorate DSS-induced UC in mice, and the mechanisms involve reduction of pro-inflammatory cytokines and selective induction of Treg cells in colons.

  18. Inhibitory Effect of Recombinant IL-25 on the Development of Dextran Sulfate Sodium Induced Experimental Colitis in Mice

    Institute of Scientific and Technical Information of China (English)

    S.S. Salum Mchenga; Danan Wang; Cheng Li; Fengping Shan; Changlong Lu

    2008-01-01

    The role of interleukin 25 (IL-25) in a number of human diseases still has not been extensively studied, here we attempt to evaluate the role of recombinant IL-25 (rIL-25) in the development of dextran sulfate sodium (DSS)induced experimental colitis. Acute colitis was induced in female C57BL/6 mice by oral administration of 2.5% DSS in drinking water ad libitum. At the same time as the start of DSS exposure, mice were injected intraperitoneally with 0.4 μg of rIL-25 or PBS. Then disease activity index (DAI), histological changes and survival rate were observed. The levels of IL-17, IL-23, and TGF-β1 in colon tissues were determined by ELISA, and the production of IL-17 by CD4+/CD8+ T cells was detected by intracellular flow cytometry. In contrast to the DSS treated mice, DSS + rIL-25 treated mice displayed a lower DAI, limited histological changes and prolonged survival. The levels of IL-23 and TGF-β1 were significantly elevated in the DSS + rIL-25 treated mice compared to the DSS treated mice. There was no significant difference in the production of IL-17 in colon tissues and CD4+/CD8+ T cells between the DSS + rIL-25 treated mice and DSS treated mice. Our findings suggest the role of IL-25 in inhibiting development and progression of acute colitis in DSS-induced mouse colitis model. Cellular & Molecular Immunology. 2008;5(6):425-431.

  19. Heme Oxygenase-1 Ameliorates Dextran Sulfate Sodium-induced Acute Murine Colitis by Regulating Th17/Treg Cell Balance*

    Science.gov (United States)

    Zhang, Liya; Zhang, Yanjie; Zhong, Wenwei; Di, Caixia; Lin, Xiaoliang; Xia, Zhenwei

    2014-01-01

    Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is a group of autoimmune diseases characterized by nonspecific inflammation in the gastrointestinal tract. Recent investigations suggest that activation of Th17 cells and/or deficiency of regulatory T cells (Treg) is involved in the pathogenesis of IBD. Heme oxygenase (HO)-1 is a protein with a wide range of anti-inflammatory and immune regulatory function, which exerts significantly protective roles in various T cell-mediated diseases. In this study, we aim to explore the immunological regulation of HO-1 in the dextran sulfate sodium-induced model of experimental murine colitis. BALB/c mice were administered 4% dextran sulfate sodium orally; some mice were intraperitoneally pretreated with HO-1 inducer hemin or HO-1 inhibitor stannum protoporphyrin IX. The results show that hemin enhances the colonic expression of HO-1 and significantly ameliorates the symptoms of colitis with improved histological changes, accompanied by a decreased proportion of Th17 cells and increased number of Tregs in mesenteric lymph node and spleen. Moreover, induction of HO-1 down-regulates retinoic acid-related orphan receptor γt expression and IL-17A levels, while promoting Treg-related forkhead box p3 (Foxp3) expression and IL-10 levels in colon. Further study in vitro revealed that up-regulated HO-1 switched the naive T cells to Tregs when cultured under a Th17-inducing environment, which involved in IL-6R blockade. Therefore, HO-1 may exhibit anti-inflammatory activity in the murine model of acute experimental colitis via regulating the balance between Th17 and Treg cells, thus providing a possible novel therapeutic target in IBD. PMID:25112868

  20. COMPARATIVE EFFICACY OF DIFFERENT REFERENCE DRUGS ON TRINITROBENZENESULFONIC ACID-INDUCED ULCERATIVE COLITIS IN THE RAT MODEL

    Directory of Open Access Journals (Sweden)

    P.S.Venkatesan

    2013-06-01

    Full Text Available Crohn’s disease and Ulcerative colitis were chronic inflammatory disorders of the bowel categorized as inflammatory bowel diseases. Trinitrobenzene sulfonic acid (TNBS-induced colitis was one of the most common methods for studying inflammatory bowel disease in animal models. Several factors may, however, affect its reproducibility, rate of animal mortality, and macroscopic and histopathological outcomes.The current study was undertaken with the objective to validate the main contributing factors to this method and compare the effects of different reference drugs upon better amelioration of trinitrobenzenesulfonic acid (TNBS induced colitis. With the above objectives, ulcerative colitis was induced by intrarectal administration of TNBS in male Wistar rats at a dose rate of 20 mg in 0.5 mL of ethanol per animal for all groups except the negative control group, which received 0.5 mL of normal saline. Different reference drugs like dexamethasone (1 mg/kg, intraperitoneally (i.p. and 2 mg/kg, orally (p.o., hydrocortisone acetate (20 mg/kg, i.p.; 20 mg/kg, enema and sulfasalazine 500mg/kg ,p.o.were administered daily once from Day 3 to 9 except the negative and positive controls which received normal saline at the rate of 10 mL/kg body weight. All the animals were sacrificed on Day 10; the colons were excised and the colon morphology and net weight of the colon segment were graded and measured, respectively. The intestinal damage had improved significantly in the experiment groups that received different reference drugs which is comparable with sulfasalazine treated group. The experimental observations, gross pathology of intestinal lesions and statistical analysis reveals no significant difference among the different reference drugs treated groups.

  1. No Protection against DSS-induced Colitis by Short-term Pretreatment with Seal or Fish Oils in Rats

    Directory of Open Access Journals (Sweden)

    Gülen Arslan

    2007-01-01

    Full Text Available Background: Omega-3 (n-3 polyunsaturated fatty acids (PUFAs have modulating effects in several chronic inflammatory conditions. The aim of the present study was to test whether prior short-term dietary supplementation with n-3 (fish or seal oil or n-6 (soy oil PUFA rich oils would protect the development of dextran sulfate sodium (DSS-induced colitis in rats.Methods: Forty-eight male Wistar rats were divided into 6 groups: no intervention, sham, DSS, seal oil + DSS, fi sh oil +DSS and soy oil + DSS. Following 7 days of acclimatisation, 1 mL oil (seal, fish or soy or distilled water (sham was administered by gavage day 8 to 14. Colitis was induced by 5% DSS in drinking water from day 15 to 21. Rats were sacrificed on day 23. Histological colitis (crypt and inflammation scores, faecal granulocyte marker protein (GMP and quantitative fatty acid composition in red blood cells were measured.Results: Pretreatment with fish or seal oils did not significantly influence DSS induced inflammation. In fact, all the oils tended to exacerbate the inflammation. Soy oil increased the mean crypt score (P < 0.04, but not the inflammation score or GMP. The ratio of n-6 to n-3 fatty acids (FAs was 11 to 1 and 10 to 1 in standard diet and in red blood cells of control rats, respectively. Following administration of DSS, the ratio fell in all treatment groups (P < 0.001. The lowest ratios were seen in the groups receiving DSS + fi sh or seal oils (around 6 to 1.Conclusion: Short-term pretreatment with fish or seal oils did not protect against subsequent induction of colitis by DSS in this rat model. Whether the high ratio of n-6 to n-3 FAs in the standard diet concealed effects of n-3 FA supplementation should be further investigated.

  2. Bilirubin prevents acute DSS-induced colitis by inhibiting leukocyte infiltration and suppressing upregulation of inducible nitric oxide synthase.

    Science.gov (United States)

    Zucker, Stephen D; Vogel, Megan E; Kindel, Tammy L; Smith, Darcey L H; Idelman, Gila; Avissar, Uri; Kakarlapudi, Ganesh; Masnovi, Michelle E

    2015-11-15

    Bilirubin is thought to exert anti-inflammatory effects by inhibiting vascular cell adhesion molecule-1 (VCAM-1)-dependent leukocyte migration and by suppressing the expression of inducible nitric oxide synthase (iNOS). As VCAM-1 and iNOS are important mediators of tissue injury in the dextran sodium sulfate (DSS) murine model of inflammatory colitis, we examined whether bilirubin prevents colonic injury in DSS-treated mice. Male C57BL/6 mice were administered 2.5% DSS in the drinking water for 7 days, while simultaneously receiving intraperitoneal injections of bilirubin (30 mg/kg) or potassium phosphate vehicle. Disease activity was monitored, peripheral blood counts and serum nitrate levels were determined, and intestinal specimens were analyzed for histological injury, leukocyte infiltration, and iNOS expression. The effect of bilirubin on IL-5 production by HSB-2 cells and on Jurkat cell transendothelial migration also was determined. DSS-treated mice that simultaneously received bilirubin lost less body weight, had lower serum nitrate levels, and exhibited reduced disease severity than vehicle-treated animals. Concordantly, histopathological analyses revealed that bilirubin-treated mice manifested significantly less colonic injury, including reduced infiltration of eosinophils, lymphocytes, and monocytes, and diminished iNOS expression. Bilirubin administration also was associated with decreased eosinophil and monocyte infiltration into the small intestine, with a corresponding increase in peripheral blood eosinophilia. Bilirubin prevented Jurkat migration but did not alter IL-5 production. In conclusion, bilirubin prevents DSS-induced colitis by inhibiting the migration of leukocytes across the vascular endothelium and by suppressing iNOS expression.

  3. Inducible chemical defences in animals

    OpenAIRE

    Heyttyey, Attila; Tóth, Zoltán; Buskirk, Josh

    2014-01-01

    Phenotypic plasticity is extremely widespread in the behaviour, morphology and life-history of animals. However, inducible changes in the production of defensive chemicals are described mostly in plants and surprisingly little is known about similar plasticity in chemical defences of animals. Inducible chemical defences may be common in animals because many are known to produce toxins, the synthesis of toxins is likely to be costly, and there are a few known cases of animals adjusting their t...

  4. Accelerated dysbiosis of gut microbiota during aggravation of DSS-induced colitis by a butyrate-producing bacterium.

    Science.gov (United States)

    Zhang, Qianpeng; Wu, Yanqiu; Wang, Jing; Wu, Guojun; Long, Wenmin; Xue, Zhengsheng; Wang, Linghua; Zhang, Xiaojun; Pang, Xiaoyan; Zhao, Yufeng; Zhao, Liping; Zhang, Chenhong

    2016-06-06

    Butyrate-producing bacteria (BPB) are potential probiotic candidates for inflammatory bowel diseases as they are often depleted in the diseased gut microbiota. However, here we found that augmentation of a human-derived butyrate-producing strain, Anaerostipes hadrus BPB5, significantly aggravated colitis in dextran sulphate sodium (DSS)-treated mice while exerted no detrimental effect in healthy mice. We explored how the interaction between BPB5 and gut microbiota may contribute to this differential impact on the hosts. Butyrate production and severity of colitis were assessed in both healthy and DSS-treated mice, and gut microbiota structural changes were analysed using high-throughput sequencing. BPB5-inoculated healthy mice showed no signs of colitis, but increased butyrate content in the gut. In DSS-treated mice, BPB5 augmentation did not increase butyrate content, but induced significantly more severe disease activity index and much higher mortality. BPB5 didn't induce significant changes of gut microbiota in healthy hosts, but expedited the structural shifts 3 days earlier toward the disease phase in BPB5-augmented than DSS-treated animals. The differential response of gut microbiota in healthy and DSS-treated mice to the same potentially beneficial bacterium with drastically different health consequences suggest that animals with dysbiotic gut microbiota should also be employed for the safety assessment of probiotic candidates.

  5. Targeted colonic claudin-2 expression renders resistance to epithelial injury, induces immune suppression, and protects from colitis.

    Science.gov (United States)

    Ahmad, R; Chaturvedi, R; Olivares-Villagómez, D; Habib, T; Asim, M; Shivesh, P; Polk, D B; Wilson, K T; Washington, M K; Van Kaer, L; Dhawan, P; Singh, A B

    2014-11-01

    Expression of claudin-2, a tight junction protein, is highly upregulated during inflammatory bowel disease (IBD) and, due to its association with epithelial permeability, has been postulated to promote inflammation. Notably, claudin-2 has also been implicated in the regulation of intestinal epithelial proliferation. However, precise role of claudin-2 in regulating colonic homeostasis remains unclear. Here, we demonstrate, using Villin-Claudin-2 transgenic mice, that increased colonic claudin-2 expression augments mucosal permeability as well as colon and crypt length. Most notably, despite leaky colon, Cl-2TG mice were significantly protected against experimental colitis. Importantly, claudin-2 expression increased colonocyte proliferation and provided protection against colitis-induced colonocyte death in a PI-3Kinase/Bcl-2-dependent manner. However, Cl-2TG mice also demonstrated marked suppression of colitis-induced increases in immune activation and associated signaling, suggesting immune tolerance. Accordingly, colons from naive Cl-2TG mice harbored significantly increased numbers of regulatory (CD4(+)Foxp3(+)) T cells than WT littermates. Furthermore, macrophages isolated from Cl-2TG mouse colon exhibited immune anergy. Importantly, these immunosuppressive changes were associated with increased synthesis of the immunoregulatory cytokine TGF-β by colonic epithelial cells in Cl-2TG mice compared with WT littermates. Taken together, our findings reveal a critical albeit complex role of claudin-2 in intestinal homeostasis by regulating epithelial permeability, inflammation and proliferation and suggest novel therapeutic opportunities. PMID:24670427

  6. Accelerated dysbiosis of gut microbiota during aggravation of DSS-induced colitis by a butyrate-producing bacterium.

    Science.gov (United States)

    Zhang, Qianpeng; Wu, Yanqiu; Wang, Jing; Wu, Guojun; Long, Wenmin; Xue, Zhengsheng; Wang, Linghua; Zhang, Xiaojun; Pang, Xiaoyan; Zhao, Yufeng; Zhao, Liping; Zhang, Chenhong

    2016-01-01

    Butyrate-producing bacteria (BPB) are potential probiotic candidates for inflammatory bowel diseases as they are often depleted in the diseased gut microbiota. However, here we found that augmentation of a human-derived butyrate-producing strain, Anaerostipes hadrus BPB5, significantly aggravated colitis in dextran sulphate sodium (DSS)-treated mice while exerted no detrimental effect in healthy mice. We explored how the interaction between BPB5 and gut microbiota may contribute to this differential impact on the hosts. Butyrate production and severity of colitis were assessed in both healthy and DSS-treated mice, and gut microbiota structural changes were analysed using high-throughput sequencing. BPB5-inoculated healthy mice showed no signs of colitis, but increased butyrate content in the gut. In DSS-treated mice, BPB5 augmentation did not increase butyrate content, but induced significantly more severe disease activity index and much higher mortality. BPB5 didn't induce significant changes of gut microbiota in healthy hosts, but expedited the structural shifts 3 days earlier toward the disease phase in BPB5-augmented than DSS-treated animals. The differential response of gut microbiota in healthy and DSS-treated mice to the same potentially beneficial bacterium with drastically different health consequences suggest that animals with dysbiotic gut microbiota should also be employed for the safety assessment of probiotic candidates. PMID:27264309

  7. The prophylactic effect of 5-aminosalicylic acid and salazosulphapyridine on degraded-carrageenan-induced colitis in guinea pigs

    DEFF Research Database (Denmark)

    Poulsen, Steen Seier

    1984-01-01

    Experimental colitis was induced in guinea pigs by administration of 5% degraded carrageenan for 5 days. The prophylactic effect of a slow-release preparation of 5-aminosalicylic acid (5-ASA; 13 mg/100 g/day) was compared with approximately equimolar amounts of salazosulphapyridine (SASP; 26 mg/100...... g/day) and placebo. Treatment was started 2 days before initiation of carrageenan administration. The drugs were administered through a chronic gastric fistula. At the end of the study concentrations of 5-ASA and acetylated 5-ASA (Ac-5-ASA) in cecal contents and in plasma were determined...... difference between the human ulcerative colitis and the carrageenan model may account for the lack of prophylactic effect of the slow-release 5-ASA in this experiment....

  8. Ibuprofen Inhibits Colitis-Induced Overexpression of TumorRelated Rac1b

    Directory of Open Access Journals (Sweden)

    Paulo Matos

    2013-01-01

    Full Text Available The serrated pathway to colorectal tumor formation involves oncogenic mutations in the BRAF gene, which are sufficient for initiation of hyperplastic growth but not for tumor progression. A previous analysis of colorectal tumors revealed that overexpression of splice variant Rac1b occurs in around 80% of tumors with mutant BRAF and both events proved to cooperate in tumor cell survival. Here, we provide evidence for increased expression of Rac1b in patients with inflamed human colonic mucosa as well as following experimentally induced colitis in mice. The increase of Rac1b in the mouse model was specifically prevented by the nonsteroidal anti-inflammatory drug ibuprofen, which also inhibited Rac1b expression in cultured HT29 colorectal tumor cells through a cyclooxygenase inhibition–independent mechanism. Accordingly, the presence of ibuprofen led to a reduction of HT29 cell survival in vitro and inhibited Rac1b-dependent tumor growth of HT29 xenografts. Together, our results suggest that stromal cues, namely, inflammation, can trigger changes in Rac1b expression in the colon and identify ibuprofen as a highly specific and efficient inhibitor of Rac1b overexpression in colorectal tumors. Our data suggest that the use of ibuprofen may be beneficial in the treatment of patients with serrated colorectal tumors or with inflammatory colon syndromes.

  9. Effect of Glucans from Caripia montagnei Mushroom on TNBS-Induced Colitis

    Directory of Open Access Journals (Sweden)

    Marilia da S. Nascimento Santos

    2014-02-01

    Full Text Available In this study, we evaluated the effect of different doses of polysaccharides extracted from Caripia montagnei mushroom at different intervals of treatment on colonic injury in the model of colitis induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS. The FT-IR analysis and NMR showed that the polysaccharides from this species of mushroom are composed of α- and β-glucans. The colonic damage was evaluated by macroscopic, histological, biochemical and immunologic analyses. The results showed the reduction of colonic lesions in all groups treated with the glucans. Such glucans significantly reduced the levels of IL-6 (50 and 75 mg/kg, p < 0.05, a major inflammatory cytokine. Biochemical analyses showed that the glucans from C. montagnei acted on reducing levels of alkaline phosphatase (75 mg/kg, p < 0.01 and myeloperoxidase (p < 0.001, a result confirmed by the reduction of cellular infiltration observed microscopically. The increase of catalase activity possibly indicates a protective effect of these glucans on colonic tissue, confirming their anti-inflammatory potential.

  10. Healing acceleration of acetic acid-induced colitis by marigold (Calendula officinalis in male rats

    Directory of Open Access Journals (Sweden)

    Nader Tanideh

    2016-01-01

    Full Text Available Background/Aim: Ulcerative colitis (UC is a type of chronic inflammatory bowel disease with unknown etiology. Several therapeutic strategies such as consumption of medicinal plants have been used for its treatment. The aim of this study was to evaluate healing effects of Calendula officinalis hydroalcoholic extract in experimentally induced UC in rat. Materials and Methods: Ninety-six rats, weighing 200 ± 20 g, were randomly divided into eight equal groups. UC induced by 3% acetic acid and oral doses of C. officinalis extract, 1500 and 3000 mg/kg, and enema (gel 10% and 20% were given. Two groups as positive controls were given asacol (enema and oral mesalamine. Negative control groups were given normal saline and base gel. On days 3 and 7, intestinal histopathology and weight changes, plus oxidative stress indices including malondialdehyde (MDA level and myeloperoxidase (MPO activity were assayed. Results: A significant increase in the body weight of rats was seen in the group given C. officinalis extract 3000 mg/kg orally, oral mesalamine, and 20% intracolonic gel form of marigold extract compared with negative control and base gel groups during the experimental period. Acute inflammation and granular atrophy after UC induction were resolved completely completely by both 20% intracolonic gel and 3000 mg/kg orally. An increase in MPO activity and a decrease in MDA level in response to oral and intracolonic gel form of C. officinalis were observed 3 and and 7 days after treatment (P < 0.05. Conclusion: Our results indicate that oral and enema forms of hydroalcoholic extract of C. officinalis can be offered as are potential therapeutic agents for UC induced in rats.

  11. Preventive effect of a pectic polysaccharide of the common cranberry Vaccinium oxycoccos L. on acetic acid-induced colitis in mice

    Institute of Scientific and Technical Information of China (English)

    Sergey V Popov; Pavel A Markov; Ida R Nikitina; Sergey Petrishev; Vasily Smirnov; Yury S Ovodov

    2006-01-01

    AIM: To study isolation and chemical characterization of pectin derived from the common cranberry Vaccinium oxycoccos L. (oxycoccusan OP) and the testing of its preventive effect on experimental colitis.METHODS: Mice were administrated orally with OP two days prior to a rectal injection of 5% acetic acid and examined for colonic damage 24 h later. Colonic inflammation was characterized by macroscopical injury and enhanced levels of myeloperoxidase activity measured spectrophotometrically with o-phenylene diamine as the substrate. The mucus contents of the colon were determined by the Alcian blue dye binding method. Vascular permeability was estimated using 4%Evans blue passage after i.p. injection of 0.05 mol/L acetic acid.RESULTS: In the mice treated with OP, colonic macroscopic scores (1.1 ± 0.4 vs 2.7, P < 0.01) and the total square area of damage (10 ± 2 vs 21 ± 7, P < 0.01)were significantly reduced when compared with the vehicle-treated colitis group. OP was shown to decrease the tissue myeloperoxidase activity in colons (42 ± 11 vs 112 ± 40, P < 0.01) and enhance the amount of mucus of colitis mice (0.9 ± 0.1 vs 0.4 ± 0.1, P < 0.01). The level of colonic malondialdehyde was noted to decrease in OP-pretreated mice (3.6 ± 0.7 vs 5.1 ± 0.8, P < 0.01).OP was found to decrease the inflammatory status of mice as was determined by reduction of vascular permeability (161 ± 34 vs 241 ± 21, P < 0.01). Adhesion of peritoneal neutrophils and macrophages was also shown to decrease after administration of OP (141 ± 50vs 235 ± 37, P < 0.05).CONCLUSION: Thus, a preventive effect of pectin from the common cranberry, namely oxycoccusan OP,on acetic acid-induced colitis in mice was detected.A reduction of neutrophil infiltration and antioxidant action may be implicated in the protective effect of oxycoccusan.

  12. Eosinophilic colitis

    Institute of Scientific and Technical Information of China (English)

    Nnenna Okpara; Bassam Aswad; Gyorgy Baffy

    2009-01-01

    Eosinophilic colitis (EC) is a rare form of primary eosinophilic gastrointestinal disease with a bimodal peak of prevalence in neonates and young adults. EC remains a little understood condition in contrast to the increasingly recognized eosinophilic esophagitis. Clinical presentation of EC is highly variable according to mucosal, transmural, or serosal predominance of inflammation. EC has a broad differential diagnosis because colon tissue eosinophilia often occurs in parasitic infection, drug-induced allergic reactions,inflammatory bowel disease, and various connective tissue disorders, which require thorough searching for secondary causes that may be specifically treated with antibiotics or dietary and drug elimination.Like eosinophilic gastrointestinal disease involving other segments of the gastrointestinal tract, EC responds very well to steroids that may be spared by using antihistamines, leukotriene inhibitors and biologics.

  13. MAG-EPA reduces severity of DSS-induced colitis in rats.

    Science.gov (United States)

    Morin, Caroline; Blier, Pierre U; Fortin, Samuel

    2016-05-15

    Ulcerative colitis (UC) is a chronic disease characterized by diffuse inflammation of the intestinal mucosa of the large bowel. Omega-3 (ω3) fatty acid supplementation has been associated with a decreased production of inflammatory cytokines involved in UC pathogenesis. The aim of this study was to determine the preventive and therapeutic potential of eicosapentaenoic acid monoglyceride (MAG-EPA) in an in vivo rats model of UC induced by dextran sulfate sodium (DSS). DSS rats were untreated or treated per os with MAG-EPA. Morphological, histological, and biochemical analyses were performed following MAG-EPA administrations. Morphological and histological analyses revealed that MAG-EPA pretreatment (12 days pre-DSS) and treatment (6 days post-DSS) exhibited strong activity in reducing severity of disease in DSS rats. Following MAG-EPA administrations, tissue levels of the proinflammatory cytokines TNF-α, IL-1β, and IL-6 were markedly lower compared with rats treated only with DSS. MAG-EPA per os administration decrease neutrophil infiltration in colon tissues, as depicted by myelohyperoxidase activity. Results also revealed a reduced activation of NF-κB pathways correlated with a decreased expression of COX-2 in colon homogenates derived from MAG-EPA-pretreated and treated rats. Tension measurements performed on colon tissues revealed that contractile responses to methacholine and relaxing effect induced by sodium nitroprusside were largely increased following MAG-EPA treatment. The combined treatment of MAG-EPA and vitamin E displayed an antagonistic effect on anti-inflammatory properties of MAG-EPA in DSS rats.

  14. CD34 is required for infiltration of eosinophils into the colon and pathology associated with DSS-induced ulcerative colitis.

    Science.gov (United States)

    Maltby, Steven; Wohlfarth, Carolin; Gold, Matthew; Zbytnuik, Lori; Hughes, Michael R; McNagny, Kelly M

    2010-09-01

    Eosinophil migration into the gut and the release of granular mediators plays a critical role in the pathogenesis of inflammatory bowel diseases, including ulcerative colitis. We recently demonstrated that eosinophil migration into the lung requires cell surface expression of the sialomucin CD34 on mast cells and eosinophils in an asthma model. Based on these findings, we investigated a similar role for CD34 in the migration of eosinophils and other inflammatory cells into the colon as well as explored the effects of CD34 ablation on disease development in a dextran sulfate sodium-induced model of ulcerative colitis. Our findings demonstrate decreased disease severity in dextran sulfate sodium-treated Cd34(-/-) mice, as assessed by weight loss, diarrhea, bleeding, colon shortening and tissue pathology, compared with wild-type controls. CD34 was predominantly expressed on eosinophils within inflamed colon tissues, and Cd34(-/-) animals exhibited drastically reduced colon eosinophil infiltration. Using chimeric animals, we demonstrated that decreased disease pathology resulted from loss of CD34 from bone marrow-derived cells and that eosinophilia in Cd34(-/-)IL5(Tg) animals was sufficient to overcome protection from disease. In addition, we demonstrated a decrease in peripheral blood eosinophil numbers following dextran sulfate sodium treatment. These findings demonstrate that CD34 was expressed on colon-infiltrating eosinophils and played a role in eosinophil migration. Further, our findings suggest CD34 is required for efficient eosinophil migration, but not proliferation or expansion, in the development of ulcerative colitis.

  15. Tomato lycopene extract prevents lipopolysaccharide-induced NF-kappaB signaling but worsens dextran sulfate sodium-induced colitis in NF-kappaBEGFP mice.

    Directory of Open Access Journals (Sweden)

    Young-Eun Joo

    Full Text Available BACKGROUND: The impact of tomato lycopene extract (TLE on intestinal inflammation is currently unknown. We investigated the effect of TLE on lipopolysaccharide (LPS-induced innate signaling and experimental colitis. METHODOLOGY/PRINCIPAL FINDINGS: Mice were fed a diet containing 0.5 and 2% TLE or isoflavone free control (AIN-76. The therapeutic efficacy of TLE diet was assessed using dextran sulfate sodium (DSS exposed mice and IL-10(-/-;NF-kappaB(EGFP mice, representing an acute and spontaneous chronic colitis model respectively. A mini-endoscope was used to determine the extent of macroscopic mucosal lesions. Murine splenocytes and intestinal epithelial cells were used to determine the in vitro impact of TLE on LPS-induced NF-kappaB signaling. In vitro, TLE blocked LPS-induced IkappaBalpha degradation, RelA translocation, NF-kappaB transcriptional activity and MIP-2 mRNA accumulation in IEC-18 cells. Moreover, LPS-induced IL-12p40 gene expression was dose-dependently inhibited in TLE-treated splenocytes. Interestingly, DSS-induced acute colitis worsened in TLE-fed NF-kappaB(EGFP mice compared to control diet as measured by weight loss, colonoscopic analysis and histological scores. In contrast, TLE-fed IL-10(-/-;NF-kappaB(EGFP mice displayed decreased colonic EGFP expression compared to control diet. IL-6, TNFalpha, and MCP-1 mRNA expression were increased in the colon of TLE-fed, DSS-exposed NF-kappaB(EGFP mice compared to the control diet. Additionally, caspase-3 activation and TUNEL positive cells were enhanced in TLE diet-fed, DSS-exposed mice as compared to DSS control mice. CONCLUSIONS/ SIGNIFICANCE: These results indicate that TLE prevents LPS-induced proinflammatory gene expression by blocking of NF-kappaB signaling, but aggravates DSS-induced colitis by enhancing epithelial cell apoptosis.

  16. Effects of Carum carvi L. (Caraway) extract and essential oil on TNBS-induced colitis in rats.

    Science.gov (United States)

    Keshavarz, A; Minaiyan, M; Ghannadi, A; Mahzouni, P

    2013-01-01

    Carum carvi L. (Apiaceae family) or caraway is a common household plant grown around the world including Iran. Caraway fruits are used as flavoring agent in foods and beverages, and have various traditional uses in ethnomedicine. Anti-inflammatory, spasmolytic, antimicrobial, antioxidant, carminative and immunomodulatory properties of caraway suggest that it might exert beneficial effects on inflammatory bowel disease (IBD). Therefore, this study was carried out to investigate the effects of caraway hydroalcoholic extract (CHE) and its essential oil (CEO) in an immunological model of colitis in rats induced by trinitrobenzene sulfonic acid (TNBS). Different doses of CHE (100, 200, 400 mg/kg) and CEO (100, 200, 400 μl/kg) were administered orally (p.o.) and also doses of CHE (100, 400 mg/kg) and CEO (100, 400 μl/kg) were given intraperitoneally (i.p.) to the separate groups of male Wistar rats (n=6). Administration of the doses started 6 h after induction of colitis and continued daily for 5 consecutive days. Wet colon weight/length ratio was measured and tissue damage scores as well as indices of colitis were evaluated both macroscopically and histopathologically. CHE and CEO at all doses tested were effective in reducing colon tissue lesions and colitis indices and the efficacy was nearly the same when different doses of plant fractions were administered p.o. or i.p. Administration of prednisolone (p.o., 4 mg/kg), Asacol® (mesalazine microgranules, p.o., 100 mg/kg) and hydrocortisone acetate (i.p., 20 mg/kg) as references were effective in reducing colon tissue injures as well. These data suggest that caraway fractions are both effective and possess anti-colitic activity irrespective of the dose and route of administration. PMID:24459470

  17. Matrix metalloproteinase 9-induced increase in intestinal epithelial tight junction permeability contributes to the severity of experimental DSS colitis.

    Science.gov (United States)

    Nighot, Prashant; Al-Sadi, Rana; Rawat, Manmeet; Guo, Shuhong; Watterson, D Martin; Ma, Thomas

    2015-12-15

    Recent studies have implicated a pathogenic role for matrix metalloproteinases 9 (MMP-9) in inflammatory bowel disease. Although loss of epithelial barrier function has been shown to be a key pathogenic factor for the development of intestinal inflammation, the role of MMP-9 in intestinal barrier function remains unclear. The aim of this study was to investigate the role of MMP-9 in intestinal barrier function and intestinal inflammation. Wild-type (WT) and MMP-9(-/-) mice were subjected to experimental dextran sodium sulfate (DSS) colitis by administration of 3% DSS in drinking water for 7 days. The mouse colonic permeability was measured in vivo by recycling perfusion of the entire colon using fluorescently labeled dextran. The DSS-induced increase in the colonic permeability was accompanied by an increase in intestinal epithelial cell MMP-9 expression in WT mice. The DSS-induced increase in intestinal permeability and the severity of DSS colitis was found to be attenuated in MMP-9(-/-) mice. The colonic protein expression of myosin light chain kinase (MLCK) and phospho-MLC was found to be significantly increased after DSS administration in WT mice but not in MMP-9(-/-) mice. The DSS-induced increase in colonic permeability and colonic inflammation was attenuated in MLCK(-/-) mice and MLCK inhibitor ML-7-treated WT mice. The DSS-induced increase in colonic surface epithelial cell MLCK mRNA was abolished in MMP-9(-/-) mice. Lastly, increased MMP-9 protein expression was detected within the colonic surface epithelial cells in ulcerative colitis cases. These data suggest a role of MMP-9 in modulation of colonic epithelial permeability and inflammation via MLCK.

  18. Plant flavonol isorhamnetin attenuates chemically induced inflammatory bowel disease via a PXR-dependent pathway

    OpenAIRE

    Dou, Wei; Zhang, Jingjing; Li, Hao; Kortagere, Sandhya; Sun, Katherine; Ding, Lili; Ren, Gaiyan; WANG Zhengtao; Mani, Sridhar

    2014-01-01

    Isorhamnetin is an O-methylated flavonol present in fruit and vegetables. We recently reported the identification of isorhamnetin as an activator of the human pregnane X receptor (PXR), a known target for abrogating inflammation in inflammatory bowel disease (IBD). The current study investigated the role of isorhamnetin as a putative mouse PXR activator in ameliorating chemically induced IBD. Using two different models (Ulcerative colitis-like and Crohn’s disease-like) of experimental IBD in ...

  19. Crohn's disease but not chronic ulcerative colitis induces the expression of PAI-1 in enteric neurons

    DEFF Research Database (Denmark)

    Laerum, O.D.; Illemann, M.; Skarstein, A.;

    2008-01-01

    by immunohistochemical techniques. RESULTS: PAI-1 was found in a subset of neurons primarily located in the submucosal plexus of the small and large intestine in 24 of 28 cases (86%) with Crohn's disease, but in none of 17 cases with chronic ulcerative colitis and other severe inflammatory conditions in the intestinal......OBJECTIVES: Chronic inflammation of the intestinal wall is the common characteristic of Crohn's disease and ulcerative colitis; disorders, which in some cases can be difficult to distinguish. The inflammation also affects the local neuronal plexuses of the enteric nervous system. It is known....... CONCLUSIONS: PAI-1-positive neurons in inflammatory bowel disease are linked to chronic inflammation in Crohn's disease, implying PAI-1 as a potential parameter for the differential diagnosis between Crohn's disease and ulcerative colitis. The findings also suggest that PAI-1 in neurons is related to pain...

  20. A Unique Case of Mycophenolate Induced Colitis after 10 Years of Use.

    Science.gov (United States)

    Goyal, Abhinav; Salahuddin, Moiz; Govil, Yogesh

    2016-01-01

    A 31-year-old female with a history of lupus nephritis on Hydroxychloroquine, Prednisone, and Mycophenolate Mofetil (MMF) for 10 years presented to the hospital for ankle swelling. On day four, she started to have severe, nonbloody, watery diarrhea with abdominal distension and tenderness. Stool PCR was negative for C. difficile. CT abdomen/pelvis showed gaseous distension of the colon without any obstruction. Flexible sigmoidoscopy revealed a normal looking mucosa. Histopathology showed crypt atrophy and increased crypt apoptosis, consistent with MMF colitis. The diarrhea resolved three days after stopping MMF. Although generally well tolerated, diarrhea is a common side effect of MMF. Most cases occur in the first six months of starting MMF. This case is unique because it describes MMF colitis in lupus after more than 10 years. Thus, MMF colitis should be considered as a differential in patients taking it, regardless of the duration of use. PMID:27668102

  1. Insights from advances in research of chemically induced experimental models of human inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Inflammatory bowel disease (IBD), the most important being Crohn's disease and ulcerative colitis, results from chronic dysregulation of the mucosal immune system in the gastrointestinal tract. Although the pathogenesis of IBD remains unclear, it is widely accepted that genetic, environmental, and immunological factors are involved. Recent studies suggest that intestinal epithelial defenses are important to prevent inflammation by protecting against microbial pathogens and oxidative stresses. To investigate the etiology of IBD, animal models of experimental colitis have been developed and are frequently used to evaluate new anti-inflammatory treatments for IBD. Several models of experimental colitis that demonstrate various pathophysiological aspects of the human disease have been described. In this manuscript, we review the characteristic features of IBD through a discussion of the various chemically induced experimental models of colitis (e.g. dextran sodium sulfate-, 2,4,6-trinitrobenzene sulfonic acid-, oxazolone-, acetic acid-, and indomethacin-induced models). We also summarize some regulatory and pathogenic factors demonstrated by these models that can, hopefully, be exploited to develop future therapeutic strategies against IBD.

  2. Stoma-Closure-Induced Fulminant Pseudomembranous Colitis Recovered by Adjunctive Intracolic Vancomycin with Postural Change

    Directory of Open Access Journals (Sweden)

    Yozo Suzuki

    2010-05-01

    Full Text Available A 67-year-old man with a history of low anterior resection and diverting loop transverse colostomy for rectal carcinoma developed fulminant pseudomembranous colitis after stoma closure. Oral administration of vancomycin at 0.5 g every 6 h and colonoscopy with intracolic vancomycin administration was unsuccessful, but continuation of intracolic vancomycin with postural change resulted in dramatic recovery. Postural change may extend the efficacy of intracolic vancomycin, and intracolic vancomycin should be considered as an option between conventional therapy and surgical intervention for pseudomembranous colitis.

  3. Psychological stress promotes neutrophil infiltration in colon tissue through adrenergic signaling in DSS-induced colitis model.

    Science.gov (United States)

    Deng, Que; Chen, Hongyu; Liu, Yanjun; Xiao, Fengjun; Guo, Liang; Liu, Dan; Cheng, Xiang; Zhao, Min; Wang, Xiaomeng; Xie, Shuai; Qi, Siyong; Yin, Zhaoyang; Gao, Jiangping; Chen, Xintian; Wang, Jiangong; Guo, Ning; Ma, Yuanfang; Shi, Ming

    2016-10-01

    Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory condition. Psychological stress has been postulated to affect the clinical symptoms and recurrence of IBD. The exact molecular mechanisms are not fully understood. In the present study, we demonstrate that psychological stress promotes neutrophil infiltration into colon tissues in dextran sulfate sodium (DSS)-induced colitis model. The psychological stress resulted in abnormal expression of the proinflammatory cytokines (IL-1β, IL-6, IL-17A, and IL-22) and neutrophil chemokines (CXCL1 and CXCL2) and overactivation of the STAT3 inflammatory signaling pathway. Under chronic unpredictable stress, the adrenergic nervous system was markedly activated, as the expression of tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis, in bone marrow and colonic epithelium was enhanced, especially in the myenteric ganglia. The β-AR agonist isoproterenol mimicked the effects of psychological stress on neutrophilia, neutrophil infiltration, and colonic damage in DSS-induced colitis. The β1-AR/β2-AR inhibitor propranolol reduced the numbers of the neutrophils in the circulation, suppressed neutrophil infiltration into colonic tissues, and attenuated the colonic tissue damage promoted by chronic stress. Propranolol also abolished stress-induced upregulation of proinflammatory cytokines and neutrophil chemokines. Our data reveal a close linkage between the β1-AR/β2-AR activation and neutrophil trafficking and also suggest the critical roles of adrenergic nervous system in exacerbation of inflammation and damage of colonic tissues in experimental colitis. The current study provides a new insight into the mechanisms underlying the association of psychological stress with excessive inflammatory response and pathophysiological consequences in IBD. The findings also suggest a potential application of neuroprotective agents to prevent relapsing immune activation in the treatment of IBD.

  4. Preventive and therapeutic effects of NF-kappaB inhibitor curcumin in rats colitis induced by trinitrobenzene sulfonic acid

    Institute of Scientific and Technical Information of China (English)

    Yan-Ting Jian; Guo-Feng Mai; Ji-De Wang; Ya-Li Zhang; Rong-Cheng Luo; Yong-Xin Fang

    2005-01-01

    AIM: To ascertain the molecule mechanism of nuclear factor-κB (NF-κB) inhibitor curcumin preventive and therapeutic effects in rats' colitis induced by trinitrobenzene sulfonic acid (TNBS).METHODS: Sixty rats with TNBS-induced colitis weretreated with 2.0% curcumin in the diet. Thirty positive control rats were treated with 0.5% sulfasalazine (SASP).Thirty negative control rats and thirty model rats were treated with general diet. Changes of body weight together with histological scores were evaluated. Survival rates were also evaluated. Cell nuclear NF-κB activity in colonic mucosa was evaluated by using electrophoretic mobility shift assay. Cytoplasmic IκB protein in colonic mucosa was detected by using Western Blot analysis.Cytokine messenger expression in colonic tissue was assessed by using semiquantitative reverse-transcription polymerase chain reaction.RESULTS: Treatment with curcumin could prevent and treat both wasting and histopathologic signs of rats with TNBS-induced intestinal inflammation. In accordance with these findings, NF-κB activation in colonic mucosa was suppressed in the curcumin-treated groups. Degradations of cytoplasmic IκB protein in colonic mucosa were blocked by curcumin treatment. Proinfiammatory cytokine messenger RNA expression in colonic mucosa was also suppressed.CONCLUSION: This study shows that NF-κB inhibitor curcumin could prevent and improve experimental colitis in murine model with inflammatory bowel disease (IBD).The findings suggest that NF-κB inhibitor curcumin could be a potential target for the patients with IBD.

  5. Possible Role of Mast Cells and Neuropeptides in the Recovery Process of Dextran Sulfate Sodium-induced Colitis in Rats

    Institute of Scientific and Technical Information of China (English)

    Ping Zhao; Lei Dong; Jin-yan Luo; Hai-tao Guan; Hui Ma; Xue-qin Wang

    2013-01-01

    Objective To clarify the role of mast cells and neuropeptides substance P (SP),somatostatin (SS),and vasoactive intestinal peptide (VIP) in dextran sulfate sodium (DSS)-induced colitis in rats. Methods Experimental colitis was induced in Sprague-Dawley rats (180-200 g,n=20) by oral in-gestion of 4% (w/v) DSS in drinking water for 7 days. Control rats (n=5) drank water and were sacrificed on day 0. Mast cell number,histamine levels in whole blood and tissue,tissue levels of SP,SS and,VIP in the dis-tal colon of the rats were measured on day 8,day 13,and day 18 of experimentation. Results Oral administration of 4% DSS solution for 7 days resulted in surface epithelial loss and crypt loss in the distal colon. Mast cell count increased on day 8 (1.75±1.09/mm vs. 0.38±0.24/mm,P<0.05) and day 13 (1.55±1.01/mm vs. 0.38±0.24/mm,P<0.05) after DSS treatment. Whole blood his-tamine levels were increased on day 8 (266.93±35.62 ng/mL vs. 76.87±32.28 ng/mL,P<0.01) and gradu-ally decreased by day 13 and day 18 after DSS treatment. Histamine levels in the distal colon were decreased on day 8 (1.77±0.65 ng/mg vs. 3.06±0.87 ng/mg,P<0.05) and recovered to control levels by day 13 after DSS treatment. SP level in the distal colon gradually increased and were raised significantly by day 13 (8777.14±3056.14 pg/mL vs. 4739.66±3299.81 pg/mL,P<0.05) after DSS treatment. SS and VIP levels in the distal colon were not changed. Conclusions Mast cell degranulation followed by histamine release may play an important role in the pathogenesis of colitis induced by DSS. SP may be a significant substance in the progression of inflamma-tion and the recovery process of DSS-induced colitis.

  6. TNF-α-induced down-regulation of CDX2 suppresses MEP1A expression in colitis

    DEFF Research Database (Denmark)

    Coskun, Mehmet; Olsen, Anders Krüger; Holm, Thomas Lindebo;

    2012-01-01

    High levels of pro-inflammatory cytokines are linked to inflammatory bowel disease (IBD). The transcription factor Caudal-related homeobox transcription factor 2 (CDX2) plays a crucial role in differentiation of intestinal epithelium and regulates IBD-susceptibility genes, including meprin 1A (ME......A). The aim was to investigate the expression of CDX2 and MEP1A in colitis; to assess if they are regulated by tumor necrosis factor-α (TNF-α), and finally to reveal if CDX2 is involved in a TNF-α-induced down-regulation of MEP1A....

  7. Naringin ameliorates acetic acid induced colitis through modulation of endogenous oxido-nitrosative balance and DNA damage in rats

    OpenAIRE

    Kumar, Venkatashivam Shiva; Rajmane, Anuchandra Ramchandra; Adil, Mohammad; Kandhare, Amit Dattatraya; Ghosh, Pinaki; Bodhankar, Subhash Laxman

    2013-01-01

    The aim of this study was to evaluate the effect of naringin on experimentally induced inflammatory bowel disease in rats. Naringin (20, 40 and 80 mg/kg) was given orally for 7 days to Wistar rats before induction of colitis by intrarectal instillation of 2 mL of 4% (v/v) acetic acid solution. The degree of colonic mucosal damage was analyzed by examining mucosal damage, ulcer area, ulcer index and stool consistency. Intrarectal administration of 4% acetic acid resulted in significant modulat...

  8. Ulcerative colitis - discharge

    Science.gov (United States)

    Inflammatory bowel disease - ulcerative colitis - discharge; Ulcerative proctitis - discharge; Colitis - discharge ... were in the hospital because you have ulcerative colitis. This is a swelling of the inner lining ...

  9. Extraintestinal Helminth Infection Limits Pathology and Proinflammatory Cytokine Expression during DSS-Induced Ulcerative Colitis: A Role for Alternatively Activated Macrophages and Prostaglandins.

    Science.gov (United States)

    Ledesma-Soto, Yadira; Callejas, Blanca E; Terrazas, César A; Reyes, Jose L; Espinoza-Jiménez, Arlett; González, Marisol I; León-Cabrera, Sonia; Morales, Rosario; Olguín, Jonadab E; Saavedra, Rafael; Oghumu, Steve; Satoskar, Abhay R; Terrazas, Luis I

    2015-01-01

    Chronic inflammation of the intestinal mucosa is characteristic of inflammatory bowel diseases such as ulcerative colitis and Crohn's disease. Helminth parasites have developed immunomodulatory strategies that may impact the outcome of several inflammatory diseases. Therefore, we investigated whether Taenia crassiceps infection is able to decrease the inflammatory effects of dextran sulfate sodium- (DSS-) induced ulcerative colitis in BALB/c and C57BL/6 mice. Preinfection significantly reduced the manifestations of DSS-induced colitis, as weight loss and shortened colon length, and decreased the disease activity index independently of the genetic background of the mice. Taenia infection decreased systemic levels of proinflammatory cytokines while increasing levels of IL-4 and IL-10, and the inflammatory infiltrate into the colon was also markedly reduced. RT-PCR assays from colon showed that T. crassiceps-infected mice displayed increased expression of Arginase-1 but decreased expression of iNOS compared to DSS-treated uninfected mice. The percentages of T regulatory cells were not increased. The adoptive transfer of alternatively activated macrophages (AAMФs) from infected mice into mice with DSS-induced colitis reduced the severity of colon inflammation. Administration of indomethacin abrogated the anticolitic effect of Taenia. Thus, T. crassiceps infection limits the pathology of ulcerative colitis by suppressing inflammatory responses mechanistically associated with AAMФs and prostaglandins.

  10. Effects of sinomenine on the expression of microRNA-155 in 2,4,6-trinitrobenzenesulfonic acid-induced colitis in mice.

    Directory of Open Access Journals (Sweden)

    Qiao Yu

    Full Text Available BACKGROUND: Sinomenine, a pure alkaloid isolated in Chinese medicine from the root of Sinomenium acutum, has been demonstrated to have anti-inflammatory and immunosuppressive effects. MicroRNAs (miRNAs are gradually being recognized as critical mediators of disease pathogenesis via coordinated regulation of molecular effector pathways. METHODOLOGY/FINDINGS: After colitis was induced in mice by instillation of 5% (w/v 2,4,6-trinitrobenzenesulfonic acid (TNBS, sinomenine at a dose of 100 or 200 mg/kg was orally administered once daily for 7 days. We evaluated body weight, survival rate, diarrhea score, histological score and myeloperoxidase (MPO activity. The mRNA and protein expression levels of miR-155, c-Maf, TNF-α and IFN-γ were determined by quantitative RT-PCR and immunohistochemistry, respectively. Sinomenine (100 or 200 mg/kg-treated mice with TNBS-induced colitis were significantly improved in terms of body weight, survival rate, diarrhea score, histological score and MPO activity compared with untreated mice. Both dosages of sinomenine significantly decreased the mRNA and protein expression levels of c-Maf, TNF-α and IFN-γ, which elevated in TNBS-induced colitis. Furthermore, sinomenine at a dose of 200 mg/kg significantly decreased the level of miR-155 expression by 71% (p = 0.025 compared with untreated TNBS-induced colitis in mice. CONCLUSIONS/SIGNIFICANCE: Our study evaluated the effects and potential mechanisms of sinomenine in the anti-inflammatory response via miRNA-155 in mice with TNBS-induced colitis. Our findings suggest that sinomenine has anti-inflammatory effects on TNBS-induced colitis by down-regulating the levels of miR-155 and several related inflammatory cytokines.

  11. Melatonin reduces bacterial translocation and apoptosis in trinitrobenzene sulphonic acid-induced colitis of rats

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    AIM:To investigate the effects of exogenous melatonin on bacterial translocation and apoptosis in a rat ulcerative colitis model.METHODS:Rats were randomly assigned to three groups:group Ⅰ:control,group Ⅱ: experimental colitis,group Ⅲ:colitis plus melatonin treatment.On d 11 after colitis,plasma tumor necrosis factor-α,portal blood endotoxin levels,colon tissue myeloperoxidase and caspase-3 activity were measured.Bacterial translocation was quantified by blood,lymph node,liver and spleen culture.RESULTS:We observed a significantly reduced incidence of bacterial translocation to the liver,spleen,mesenteric lymph nodes,portal and systemic blood in animals treated with melatonin.Treatment with melatonin significantly decreased the caspase-3 activity in colonic tissues compared to that in trinitrobenzene sulphonic acid-treated rats (16.11 ± 2.46 vs 32.97 ± 3.91,P < 0.01).CONCLUSION:Melatonin has a protective effect on bacterial translocation and apoptosis.

  12. Black tea extract prevents lipopolysaccharide-induced NF-κB signaling and attenuates dextran sulfate sodium-induced experimental colitis

    Directory of Open Access Journals (Sweden)

    Cho Sung-Bum

    2011-10-01

    Full Text Available Abstract Background Black tea has been shown to elicit anti-oxidant, anti-carcinogenic, anti-inflammatory and anti-mutagenic properties. In this study, we investigated the impact of black tea extract (BTE on lipopolysaccharide (LPS-induced NF-κB signaling in bone marrow derived-macrophages (BMM and determined the therapeutic efficacy of this extract on colon inflammation. Methods The effect of BTE on LPS-induced NF-κB signaling and pro-inflammatory gene expression was evaluated by RT-PCR, Western blotting, immunofluorescence and electrophoretic mobility shift assay (EMSA. The in vivo efficacy of BTE was assessed in mice with 3% dextran sulfate sodium (DSS-induced colitis. The severity of colitis was measured by weight loss, colon length and histologic scores. Results LPS-induced IL-12p40, IL-23p19, IL-6 and IL-1β mRNA expressions were inhibited by BTE. LPS-induced IκBα phosphorylation/degradation and nuclear translocation of NF-κB/p65 were blocked by BTE. BTE treatment blocked LPS-induced DNA-binding activity of NF-κB. BTE-fed, DSS-exposed mice showed the less weight loss, longer colon length and lower histologic score compared to control diet-fed, DSS-exposed mice. DSS-induced IκBα phosphorylation/degradation and phosphorylation of NF-κB/p65 were blocked by BTE. An increase of cleaved caspase-3 and poly (ADP-ribose polymerase (PARP in DSS-exposed mice was blocked by BTE. Conclusions These results indicate that BTE attenuates colon inflammation through the blockage of NF-κB signaling and apoptosis in DSS-induced experimental colitis model.

  13. Microscopic colitis

    DEFF Research Database (Denmark)

    Münch, A; Aust, D; Bohr, Jakob;

    2012-01-01

    Microscopic colitis (MC) is an inflammatory bowel disease presenting with chronic, non-bloody watery diarrhoea and few or no endoscopic abnormalities. The histological examination reveals mainly two subtypes of MC, lymphocytic or collagenous colitis. Despite the fact that the incidence in MC has...... been rising over the last decades, research has been sparse and our knowledge about MC remains limited. Specialists in the field have initiated the European Microscopic Colitis Group (EMCG) with the primary goal to create awareness on MC. The EMCG is furthermore a forum with the intention to promote...

  14. The Algal Meroterpene 11-Hydroxy-1′-O-Methylamentadione Ameloriates Dextran Sulfate Sodium-Induced Colitis in Mice

    Science.gov (United States)

    Zbakh, Hanaa; Talero, Elena; Avila, Javier; Alcaide, Antonio; de los Reyes, Carolina; Zubía, Eva; Motilva, Virginia

    2016-01-01

    Inflammatory bowel disease (IBD) is a complex class of immune disorders. Unfortunately, a treatment for total remission has not yet been found, while the use of natural product-based therapies has emerged as a promising intervention. The present study was aimed to investigate the anti-inflammatory effects of the algal meroterpene 11-hydroxy-1′-O-methylamentadione (AMT-E) in a murine model of dextran sodium sulphate (DSS)-induced colitis. AMT-E was orally administered daily (1, 10, and 20 mg/kg animal) to DSS treated mice (3% w/v) for 7 days. AMT-E prevented body weight loss and colon shortening and effectively attenuated the extent of the colonic damage. Similarly, AMT-E increased mucus production and reduced myeloperoxidase activity (marker for anti-inflammatory activity). Moreover, the algal meroterpene decreased the tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-10 levels, and caused a significant reduction of the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Our results demonstrate the protective effects of AMT-E on experimental colitis, provide an insight of the underlying mechanisms of this compound, and suggest that this class of marine natural products might be an interesting candidate for further studies on the prevention/treatment of IBD. PMID:27527191

  15. Effects of a Combination of Thyme and Oregano Essential Oils on TNBS-Induced Colitis in Mice

    Directory of Open Access Journals (Sweden)

    Juraj Koppel

    2007-10-01

    Full Text Available We examined the anti-inflammatory effects of the combination of thyme and oregano essential oil dietary administered at three concentrations (0.4% thyme and 0.2% oregano oils; 0.2% thyme and 0.1% oregano oils; 0.1% thyme and 0.05% oregano oils on mice with TNBS-induced colitis. Treatment of colitic animals with the essential oils decreased the mRNA levels of pro-inflammatory cytokines IL-1β, IL-6, GM-CSF, and TNFα, especially after application of the medium dose. The medium dose of the essential oils significantly lowered the amount of IL-1β and IL-6 proteins too. Moreover, administration of the medium dose decreased the mortality rate, accelerated the body weight gain recovery, and reduced the macroscopic damage of the colonic tissue. Our results indicate that combined treatment with appropriate concentrations of thyme and oregano essential oils can reduce the production of proinflammatory cytokines, and thereby attenuate TNBS-induced colitis in mice.

  16. The Algal Meroterpene 11-Hydroxy-1'-O-Methylamentadione Ameloriates Dextran Sulfate Sodium-Induced Colitis in Mice.

    Science.gov (United States)

    Zbakh, Hanaa; Talero, Elena; Avila, Javier; Alcaide, Antonio; de Los Reyes, Carolina; Zubía, Eva; Motilva, Virginia

    2016-01-01

    Inflammatory bowel disease (IBD) is a complex class of immune disorders. Unfortunately, a treatment for total remission has not yet been found, while the use of natural product-based therapies has emerged as a promising intervention. The present study was aimed to investigate the anti-inflammatory effects of the algal meroterpene 11-hydroxy-1'-O-methylamentadione (AMT-E) in a murine model of dextran sodium sulphate (DSS)-induced colitis. AMT-E was orally administered daily (1, 10, and 20 mg/kg animal) to DSS treated mice (3% w/v) for 7 days. AMT-E prevented body weight loss and colon shortening and effectively attenuated the extent of the colonic damage. Similarly, AMT-E increased mucus production and reduced myeloperoxidase activity (marker for anti-inflammatory activity). Moreover, the algal meroterpene decreased the tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-10 levels, and caused a significant reduction of the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Our results demonstrate the protective effects of AMT-E on experimental colitis, provide an insight of the underlying mechanisms of this compound, and suggest that this class of marine natural products might be an interesting candidate for further studies on the prevention/treatment of IBD. PMID:27527191

  17. Effect of Matricaria aurea (Loefl. Shultz-Bip. Hydroalcoholic Extract on Acetic Acid-Induced Acute Colitis in Rats

    Directory of Open Access Journals (Sweden)

    Mohsen Minaiyan

    Full Text Available Objective(s Matricaria aurea is found abundant in Iran and has large similarities in constituents especially essential oils, flavones and flavonoides as well as traditional uses to the main species; Matricaria recutita L. Anti-inflammatory, antioxidant and spasmolytic properties of the main species suggest that this plant may have beneficial effects on inflammatory bowel diseases so the present study was carried out.Materials and MethodsHydroalcoholic extract of plant with doses of 200, 400, 800 mg/kg were administered orally (p.o. for 5 days and rectally (i.r. (400 and 800 mg/kg at 15 and 2 hr before ulcer induction. To induce colitis, 2 ml of acetic acid 4% was instilled intra-colonically to separate groups of male Wistar rats (n= 6. Normal saline (2 ml, prednisolone (4 mg/kg and hydrocortisone acetate (20 mg/kg enema were administered to control and reference groups respectively. The tissue injures were assessed macroscopically and histopathologically. ResultsGreater doses of extract (400 and 800 mg/kg reduced colon weight/length ratio (P< 0.01 and the highest test dose (800 mg/kg p.o. or i.r. was effective to decrease tissue damage parameters including ulcer severity, area and index (P< 0.01 as well as inflammation severity and extent, crypt damage and total colitis index (P< 0.01 significantly. ConclusionIt is concluded that Matricaria aurea extract was effective to protect against acute colitis in acetic acid model and this effect was more significant with the greater doses administered orally or rectally. Further studies are warranted to ascertain the mechanisms that are involved and the responsible active constituents.

  18. Serotonin-Exacerbated DSS-Induced Colitis Is Associated with Increase in MMP-3 and MMP-9 Expression in the Mouse Colon.

    Science.gov (United States)

    Chen, Menglu; Gao, Lei; Chen, Pan; Feng, Dandan; Jiang, Yalin; Chang, Yongchao; Jin, Jianjun; Chu, Fong-Fong; Gao, Qiang

    2016-01-01

    Background. 5-HT enhances dextran sulfate sodium- (DSS-) induced colitis and is involved in inflammatory bowel disease (IBD). Matrix metalloproteinases (MMPs) play roles in the process of intestinal inflammation. Aims. To examine whether 5-HT induces MMPs expression in mouse colon to enhance DSS-induced colitis. Materials and Methods. C57BL/6J (B6) mice were treated with either low-dose (1.0 mg/kg) or high-dose (2.0 mg/kg) 5-HT by enema, low-dose (1.0%) or high-dose (2.5%) DSS, or combined low-dose (1.0%) DSS and (1.0 mg/kg) 5-HT. Mouse colitis was analyzed. MMPs and tissue inhibitors of MMPs (TIMPs) mRNA were measured by real-time quantitative RT-PCR in mouse colon and in human Caco-2 cells and neutrophils. MMP-3 and MMP-9 protein levels were quantified from immunohistochemistry (IHC) images of mouse colons. Results. 5-HT exacerbated DSS-induced colitis, low-dose 5-HT induces both MMP-3 and MMP-9, and high-dose 5-HT only increased MMP-3 mRNA expression in mouse colon. Mouse colon MMP-3 and MMP-9 protein levels were also elevated by 5-HT treatment. The MMP-2, TIMP-1, and TIMP-2 mRNA levels were increased in the inflamed colon. 5-HT induced MMP-3 and MMP-9 mRNA expression in Caco-2 and human neutrophils, respectively, in vitro. Conclusion. 5-HT induced MMP-3 and MMP-9 expression in mouse colon; these elevated MMPs may contribute to DSS-induced colitis.

  19. [Collagenous colitis].

    Science.gov (United States)

    Lindström, C G

    1991-05-01

    Collagenous colitis is now regarded by an overwhelming majority of authors as a clinicopathological entity and has been taken up as a such in many text-books and diagnostic atlases (Morson & Dawson, 1990, Fenoglio-Preiser et al., 1989, Whitehead 1985, Whitehead 1989). A good, detailed review of cases of collagenous colitis published up to 1988 was performed by Perri et al. Collagenous colitis was also presented to a wider medical public through a clinicopathological conference case at Massachusetts General Hospital (Case 29-1988). Finally it may be added that collagenous colitis has been included in the new fourth edition of Robbins Pathologic Basis of Disease (Cotran, Kumar, Robbins, 1989), where the possibility of an autoimmune disease is stressed.

  20. Curcumin represses the activity of inhibitor-κB kinase in dextran sulfate sodium-induced colitis by S-nitrosylation.

    Science.gov (United States)

    Kao, Ning-Jo; Hu, Jia-Yuan; Wu, Chien-Sheng; Kong, Zwe-Ling

    2016-09-01

    In this study, we investigated the preventive effects of curcumin using dextran sulfate sodium (DSS)-induced colitis and the potential role of curcumin in regulation of anti-inflammation through S-nitrosylation. After curcumin treatment for 6days, the body weight and disease activity index of DSS-induced mice was alleviated and the colonic length was also rescued. Western blot presented that the protein expression of iNOS can be reduced by curcumin. Consistently, mRNA level of iNOS and pro-inflammatory cytokines, such as TNFα, IL-1β, and IL-6, was also repressed. Moreover, Curcumin reduced the amount of nitrite in DSS-induced colitis but not affected total S-nitrosylation level on proteins on day 6, indicating that curcumin inhibited NO oxidation. Furthermore, the protection of S-nitrosylation on IKKβ in DSS-induced colitis for 6days by curcumin caused the repression of IκB phosphorylation and NF-κB activation. In conclusion, this study verified that curcumin-mediated S-nitrosylation may be as an important regulator for anti-inflammation in DSS-induced colitis of mice. PMID:27233000

  1. Mesalamine induced symptom exacerbation of ulcerative colitis: Case report and brief discussion

    Institute of Scientific and Technical Information of China (English)

    Maneesh; Kumar; Gupta; Scott; Pollack; John; J; Hutchings

    2010-01-01

    This paper describes a rare case in which the oral ad-ministration of mesalamine resulted in the exacerbation of ulcerative colitis (UC) in a patient who was previously responsive to mesalamine and whose colitis had been in remission for eight years. Mesalamine and other 5-ami-nosalicylic acid compounds are the mainstay of treatment for UC; however up to 8% of patients are unable to take the medications due to intolerance or hypersensitivity reactions. Common drug reactions are fever, nausea, di-arrhea and abdominal pain; however, exacerbation of UC has rarely been reported. This study highlights the impor-tance of ruling out mesalamine as the causative agent in cases of UC exacerbations.

  2. Microscopic colitis

    Institute of Scientific and Technical Information of China (English)

    Gianluca Ianiro; Giovanni Cammarota; Luca Valerio; Brigida Eleonora Annicchiarico; Alessandro Milani; Massimo Siciliano; Antonio Gasbarrini

    2012-01-01

    Microscopic colitis may be defined as a clinical syndrome,of unknown etiology,consisting of chronic watery diarrhea,with no alterations in the large bowel at the endoscopic and radiologic evaluation.Therefore,a definitive diagnosis is only possible by histological analysis.The epidemiological impact of this disease has become increasingly clear in the last years,with most data coming from Western countries.Microscopic colitis includes two histological subtypes [collagenous colitis (CC) and lymphocytic colitis (LC)] with no differences in clinical presentation and management.Collagenous colitis is characterized by a thickening of the subepithelial collagen layer that is absent in LC.The main feature of LC is an increase of the density of intra-epitll lial lymphocytes in the surface epithelium.A number of pathogenetic theories have been proposed over the years,involving the role of luminal agents,autoimmunity,eosinophils,genetics (human leukocyte antigen),biliary acids,infections,alterations of pericryptal fibroblasts,and drug intake; drugs like ticlopidine,carbamazepine or ranitidine are especially associated with the development of LC,while CC is more frequently linked to cimetidine,non-steroidal antiinflammatory drugs and lansoprazole.Microscopic colitis typically presents as chronic or intermittent watery diarrhea,that may be accompanied by symptoms such as abdominal pain,weight loss and incontinence.Recent evidence has added new pharmacological options for the treatment of microscopic colitis:the role of steroidal therapy,especially oral budesonide,has gained relevance,as well as immunosuppressive agents such as azathioprine and 6-mercaptopurine.The use of anti-tumor necrosis factor-α agents,infliximab and adalimumab,constitutes a new,interesting tool for the treatment of microscopic colitis,but larger,adequately designed studies are needed to confirm existing data.

  3. Immunoglobulin leakiness in scid mice with CD4(+) T-cell-induced chronic colitis

    DEFF Research Database (Denmark)

    Brimnes, J; Reimann, J; Claesson, Mogens Helweg

    2000-01-01

    development. In the present work we have investigated the relationship between disease progression and patterns or levels of Ig isotypes in the feces of scid mice suffering from an ongoing colitis. The data clearly showed that the severity or progression of the disease did not influence the levels of IgA, Ig......G1, IgG2a, IgG2b, and IgG3, whereas the level of fecal IgM increased during the course of colitis. The presence of the serum protein alpha-1-antitrypsin in fecal extracts from diseased mice suggests that some of the fecal Ig has leaked through the inflamed epithelial membrane into the gut lumen....... Finally, Ig-containing cells were observed in mesenteric lymph nodes and in the spleen, suggesting that the fecal Ig is produced both systemically and locally in the gut wall. In conclusion, the present results demonstrate that the level of IgM increases as colitis progresses. Also, the five remaining...

  4. Activation of Cannabinoid Receptor 2 Ameliorates DSS-Induced Colitis through Inhibiting NLRP3 Inflammasome in Macrophages.

    Science.gov (United States)

    Ke, Ping; Shao, Bo-Zong; Xu, Zhe-Qi; Wei, Wei; Han, Bin-Ze; Chen, Xiong-Wen; Su, Ding-Feng; Liu, Chong

    2016-01-01

    Activation of cannabinoid receptor 2 (CB2R) ameliorates inflammation, but the underlying mechanism remains unclear. In the present study, we examined whether activation of CB2R could suppress the nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome. In peritoneal macrophages isolated from C57BL/6 mice, LPS/DSS challenge for 24 h increased the expression of the components of NLRP3 inflammasome NLRP3, Casp-1 p20/Casp-1 p45 ratio, proIL-1β and IL-1β and also enhanced autophagy (LC3-II/LC3-I ratio, Beclin-1 and SQSTM1). Pretreatment of peritoneal macrophages with HU 308, a selective CB2R agonist, attenuated LPS/DSS-induced NLRP3 inflammasome activation, but further enhanced autophagy. In comparison with wild-type (WT) control, peritoneal macrophages from CB2R knockout (KO) mice had more robust NLRP3 inflammasome activation and attenuated autophagy upon LPS/DSS challenge. Knockdown autophagy-related gene 5 (Atg5) with a siRNA in peritoneal macrophages attenuated the inhibitory effects of HU 308 on LPS/DSS-induced NLRP3 inflammasome activation in vitro. In vivo, HU308 treatment attenuated DSS-induced colitis mice associated with reduced colon inflammation and inhibited NLRP3 inflammasome activation in wild-type mice. In CB2R KO mice, DSS-induced inflammation and NLRP3 inflammasome activation were more pronounced than those in WT control. Finally, we demonstrated that AMPK-mTOR-P70S6K signaling pathway was involved in this CB2R-mediated process. We conclude that activation of CB2R ameliorates DSS-induced colitis through enhancing autophagy that may inhibit NLRP3 inflammasome activation in macrophages.

  5. Efficacy of thalidomide on trinitrobenzene sulfonate-induced colitis in young rats and its mechanism

    Institute of Scientific and Technical Information of China (English)

    Xu Jiahua; Zheng Cuifang; Huang Ying; Liang Yingjie

    2014-01-01

    Background Thalidomide could relieve clinical symptoms and intestinal mucosal lesions effectively in children with refractory inflammatory bowel disease (IBD) from the pre-clinical study.This study aimed to observe the therapeutic effect of thalidomide by the established animal model of IBD model of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in Sprague-Dawley (SD) rats and to investigate the possible mechanism of action.Methods A total of 82 SD rats of about 4-5 weeks were randomly divided into three groups:the control group (25 rats),TNBS-treated group (29 rats),and thalidomide treatment group (28 rats).Daily activities were recorded.At least eight rats from each group were killed on the 4th,7th,and 14th days.Morphological and histological changes in the colon were individually assessed.Serum was collected and the levels of TNF-α and interleukins (IL-1β and IL-10) were assayed by ELISA method.The expression of colonic mucosal nuclear factor (NF)-KB was assayed with the immunohistochemical method.Results (1) In the control group,diarrhea and rectal bleeding recovered rapidly and no death was recorded.In the TNBS-treated group,diarrhea and rectal bleeding persisted for a longer time.The mortality rate was 10.34% during the observation period.In the thalidomide treatment group,diarrhea and rectal bleeding persisted for a significantly shorter time than the TNBS-treated group (P <0.01).The rats of this group also exhibited faster weight gain on day 7 compared with the TNBS-treated group but still lower than that of the control group.The mortality rate of the thalidomide treatment group was 3.57%.(2) Macroscopic and microscopic scores of the thalidomide-treated group were significantly lower than those of the TNBS model group on the 14th day (P <0.01).These results suggested faster and better colonic recovery in the thalidomide-treated group.(3) NF-KB expression in the colonic mucosa of the control group was lower than in the others

  6. The ANXA1 released from intestinal epithelial cells alleviate DSS-induced colitis by improving NKG2A expression of Natural Killer cells.

    Science.gov (United States)

    Zou, Z; Zuo, D; Yang, J; Fan, H

    2016-09-01

    Inflammatory bowel disease (IBD) arises when intestinal immune homeostasis is broken, the maintenance of such homeostasis is principally controlled by cross talk between commensal bacteria, mucosal immune cells and intestinal epithelial cells (IECs). IECs can prevent the contact between luminal bacteria with immune cells through the formation of a physical barrier and the expression of antimicrobial peptides to maintain intestinal immune homeostasis. During Colitis the IECs can express increased ANXA1, which is important for regeneration of intestinal mucosa and function as a potent anti-inflammatory protein. Natural Killer (NK) cells can also suppress the progression of colitis. It is uncertain about the effect of the cross-talk between injured IECs and recruited NK cells during colitis. In this study, the expression of ANXA1 in IECS from DSS treated mice was increased, and more NK cells were recruited to intestinal mucosa. In addition, the expression of NKG2A was upregulated when co-cultured with NK cells. The results further proved that overexpression of NKG2A in NK cells was important for inhibiting the recruitment and activity of neutrophils to alleviate DSS-induced colitis. Here, we provide a new anti-inflammation mechanism about ANXA1 secreted from injured IECs, where ANXA1 can stimulate the expression of NKG2A in NK cells that affect the recruitment and activity of neutrophils necessary for pathology of colitis.

  7. Orally administered lactoperoxidase ameliorates dextran sulfate sodium-induced colitis in mice by up-regulating colonic interleukin-10 and maintaining peripheral regulatory T cells.

    Science.gov (United States)

    Shin, Kouichirou; Horigome, Ayako; Yamauchi, Koji; Yaeshima, Tomoko; Iwatsuki, Keiji

    2009-11-01

    We previously demonstrated orally administered bovine lactoperoxidase (LPO) ameliorated dextran sulfate sodium-induced colitis in mice. Here, we examine the mechanism of action of LPO. Three days after colitis induction, expression of interferon-gamma mRNA in colonic tissue was significantly decreased in mice administered LPO; while mRNA expression of interleukin (IL)-10 and regulatory T cell (Treg) marker, Foxp3, were significantly increased. The proportion of CD4+CD25+ Tregs in peripheral CD4+ T cells was also significantly elevated when LPO was administered. Nine days after colitis induction, the severity of colitis symptoms, including body weight loss and colon shortening, was reduced and expression of IL-10 mRNA was increased in mice administered LPO. The proportion of CD4+CD25+ Tregs in peripheral leukocytes was also significantly elevated when LPO was administered. These results suggest LPO ameliorates colitis by up-regulating colonic anti-inflammatory cytokines and maintaining peripheral regulatory T cells.

  8. Lactobacillus curvatus WiKim38 isolated from kimchi induces IL-10 production in dendritic cells and alleviates DSS-induced colitis in mice.

    Science.gov (United States)

    Jo, Sung-Gang; Noh, Eui-Jeong; Lee, Jun-Young; Kim, Green; Choi, Joo-Hee; Lee, Mo-Eun; Song, Jung-Hee; Chang, Ji-Yoon; Park, Jong-Hwan

    2016-07-01

    Probiotics such as lactobacilli and bifidobacteria have healthpromoting effects by immune modulation. In the present study, we examined the immunomodulatory properties of Lactobacillus curvatus WiKim38, which was newly isolated from baechu (Chinese cabbage) kimchi. The ability of L. curvatus WiKim38 to induce cytokine production in bone marrow-derived dendritic cells (BMDCs) was determined by enzyme-linked immunosorbent assay. To evaluate the molecular mechanisms underlying L. curvatus Wikim38-mediated IL-10 production, Western blot analyses and inhibitor assays were performed. Moreover, the in vivo anti-inflammatory effects of L. curvatus WiKim38 were examined in a dextran sodium sulfate (DSS)-induced colitis mouse model. L. curvatus WiKim38 induced significantly higher levels of IL-10 in BMDCs compared with that induced by LPS. NF-κB and ERK were activated by L. curvatus WiKim38, and an inhibitor assay revealed that these pathways were required for L. curvatus WiKim38-induced production of IL-10 in BMDCs. An in vivo experiment showed that oral administration of L. curvatus WiKim38 increased the survival rate of mice with DSS-induced colitis and improved clinical signs and histopathological severity in colon tissues. Taken together, these results indicate that L. curvatus Wikim38 may have health-promoting effects via immune modulation, and may thus be applicable for therapy of various inflammatory diseases.

  9. Lactobacillus curvatus WiKim38 isolated from kimchi induces IL-10 production in dendritic cells and alleviates DSS-induced colitis in mice.

    Science.gov (United States)

    Jo, Sung-Gang; Noh, Eui-Jeong; Lee, Jun-Young; Kim, Green; Choi, Joo-Hee; Lee, Mo-Eun; Song, Jung-Hee; Chang, Ji-Yoon; Park, Jong-Hwan

    2016-07-01

    Probiotics such as lactobacilli and bifidobacteria have healthpromoting effects by immune modulation. In the present study, we examined the immunomodulatory properties of Lactobacillus curvatus WiKim38, which was newly isolated from baechu (Chinese cabbage) kimchi. The ability of L. curvatus WiKim38 to induce cytokine production in bone marrow-derived dendritic cells (BMDCs) was determined by enzyme-linked immunosorbent assay. To evaluate the molecular mechanisms underlying L. curvatus Wikim38-mediated IL-10 production, Western blot analyses and inhibitor assays were performed. Moreover, the in vivo anti-inflammatory effects of L. curvatus WiKim38 were examined in a dextran sodium sulfate (DSS)-induced colitis mouse model. L. curvatus WiKim38 induced significantly higher levels of IL-10 in BMDCs compared with that induced by LPS. NF-κB and ERK were activated by L. curvatus WiKim38, and an inhibitor assay revealed that these pathways were required for L. curvatus WiKim38-induced production of IL-10 in BMDCs. An in vivo experiment showed that oral administration of L. curvatus WiKim38 increased the survival rate of mice with DSS-induced colitis and improved clinical signs and histopathological severity in colon tissues. Taken together, these results indicate that L. curvatus Wikim38 may have health-promoting effects via immune modulation, and may thus be applicable for therapy of various inflammatory diseases. PMID:27350616

  10. Flt3/Flt3L Participates in the Process of Regulating Dendritic Cells and Regulatory T Cells in DSS-Induced Colitis

    Directory of Open Access Journals (Sweden)

    Jing-Wei Mao

    2014-01-01

    Full Text Available The immunoregulation between dendritic cells (DCs and regulatory T cells (T-regs plays an important role in the pathogenesis of ulcerative colitis (UC. Recent research showed that Fms-like tyrosine kinase 3 (Flt3 and Flt3 ligand (Flt3L were involved in the process of DCs regulating T-regs. The DSS-induced colitis model is widely used because of its simplicity and many similarities with human UC. In this study, we observe the disease activity index (DAI and histological scoring, detect the amounts of DCs and T-regs and expression of Flt3/Flt3L, and investigate Flt3/Flt3L participating in the process of DCs regulating T-regs in DSS-induced colitis. Our findings suggest that the reduction of Flt3 and Flt3L expression may possibly induce colonic immunoregulatory imbalance between CD103+MHCII+DCs and CD4+CD25+FoxP3+T-regs in DSS-induced colitis. Flt3/Flt3L participates in the process of regulating DCS and T-regs in the pathogenesis of UC, at least, in the acute stage of this disease.

  11. Sarcodon aspratus Extract Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mouse Colon and Mesenteric Lymph Nodes.

    Science.gov (United States)

    Chung, Min-Yu; Hwang, Jin-Taek; Kim, Jin Hee; Shon, Dong-Hwa; Kim, Hyun-Ku

    2016-05-01

    Mushrooms have been previously investigated for their immune-modulating and anti-inflammatory properties. We examined whether the anti-inflammatory properties of Sarcodon aspratus ethanol extract (SAE) could elicit protective effects against dextran sulfate sodium (DSS)-induced colitis in vivo. Male C57/BL6 mice were randomly assigned to 1 of 4 treatment groups: control (CON; n = 8), DSS-treated (DSS; n = 9), DSS+SAE at 50 mg/kg BW (SAE50; n = 8), and DSS+SAE at 200 mg/kg BW groups (SAE200; n = 9). DSS treatment induced significant weight loss, which was significantly recovered by SAE200. Although SAE did not affect DSS-mediated reductions in colon length, it improved diarrhea and rectal bleeding induced by DSS. SAE at 200 mg/kg BW significantly attenuated IL-6 and enhanced IL-10 expression in mesenteric lymph nodes (MLN), and significantly reduced IL-6 levels in splenocytes. SAE200 also significantly attenuated DSS-induced increase in IL-6 and IL-1β, and reductions in IL-10 in colon tissue. High levels of SAE were also observed to significantly decrease inflammatory COX-2 expression that was upregulated by DSS in mice colon. These findings may have relevance for novel therapeutic strategies to mitigate inflammatory bowel disease-relevant inflammatory responses, via the direct and indirect anti-inflammatory activity of SAE. We also found that SAE harbors significant quantities of total fiber and β-glucan, suggesting a possible role for these components in protection against DSS-mediated colitis.

  12. Anti-inflammatory effect of Pistacia atlantica subsp. kurdica volatile oil and gum on acetic acid-induced acute colitis in rat

    Directory of Open Access Journals (Sweden)

    M. Minaiyan

    2015-04-01

    Full Text Available Background and objectives: Baneh tree or Pistacia atlantica subsp. kurdica is an endemic plant of Iran which belongs to Anacardiaceae family. It has various traditional uses including astringent and anti-diarrheal as well as improving some of the symptoms of gastrointestinal upsets. In this study we decided to investigate the effects of various fractions of baneh gum with different doses in an animal model of ulcerative colitis as one of the important chronic inflammatory bowel diseases of the gastrointestinal tract. Methods: The volatile oil and aqueous baneh gum suspensions were prepared and the constituents of the volatile oil were analyzed by GC/MS. They were used to treat colitis induced by acetic acid 4% in rats. Three doses of gum (100, 200 and 400 mg/kg were administered both orally (p.o. and intra-rectally (i.r. while volatile oil was administered p.o. with doses 100, 200 and 400 µl/kg for four constitutive days. Anti-inflammatory effects of the test compounds were compared with oral prednisolone and hydrocortisone enema. Wet colon weight/ length ratio and tissue damage scores and area as well as indices of colitis and tissue myeloperoxidase activity were evaluated for each specimen. Results: Alpha-pinene was the main constituent of baneh volatile oil (41.23%. We observed therapeutic effects in applied doses of oral gum as well as volatile oil to reduce all indices of colitis and myeloperoxidase activity. Unlike the oral form of gum, its rectal administration was not significantly effective to improve colitis. Conclusion: This research has proved the anti-inflammatory potential of oral gum of Pistacia atlantica subsp. kurdica and its volatile oil in an experimentally induced colitis.

  13. Gingko biloba extract (Ginaton) ameliorates dextran sulfate sodium (DSS)-induced acute experimental colitis in mice via reducing IL-6/STAT3 and IL-23/IL-17.

    Science.gov (United States)

    Sun, Yan; Lin, Lian-Jie; Lin, Yan; Sang, Li-Xuan; Jiang, Min; Zheng, Chang-Qing

    2015-01-01

    This study explored the underlying mechanism of Gingko biloba extract (Ginaton) on dextran sulfate sodium (DSS)-induced acute experimental colitis in mice. 40 male C57BL/6 mice were randomly divided into four groups: normal control group, Ginaton group, Ginaton treatment group, and DSS group. After 7 days administration, mice were sacrificed and colons were collected for H-E staining, immunohistochemistry, real-time PCR and Western blot. By observing clinical disease activity and histological damage, we assessed the effect of Ginaton on DSS-induced acute experimental colitis in mice and observed the effect of Ginaton on normal mice. We also explored the specific mechanism of Ginaton on DSS-induced acute experimental colitis in mice through examining the expression of inflammatory related mediators (gp130, STAT3, p-STAT3, ROR-γt) and cytokines (IL-6, IL-17, IL-23). Ginaton-treated DSS mice showed significant improvement over untreated DSS mice. Specifically, Ginaton improved clinical disease activity (DAI score, weight closs, colon shortening, and bloody stool) and histological damage, and reduced the expression of inflammatory-related mediators (p-STAT3, gp130, ROR-γt) and cytokines (IL-6, IL-17, IL-23). In addition, clinical disease activity, histological damage, the expression of inflammatory related mediators (STAT3, p-STAT3, gp130, ROR-t) and cytokines (IL-6, IL-17, IL-23) in mice of Ginaton group were similar to normal control group. In conclusion, Ginaton ameliorates DSS-induced acute experimental colitis in mice by reducing IL-17 production, which is at least partly involved in inhibiting IL-6/STAT3 signaling pathway and IL-23/IL-17 axis. Moreover, Ginaton itself does not cause inflammatory change in normal mice. These results support that Ginaton can be as a potential clinical treatment for ulcerative colitis (UC).

  14. Colitis ulcerosa

    DEFF Research Database (Denmark)

    Nielsen, Ole Haagen; Jess, Tine; Bjerrum, Jacob Tveiten;

    2013-01-01

    Ulcerative colitis (UC) is a prevalent inflammatory bowel disease of the colonic mucosa affecting approximately 20,000-25,000 Danes. Apart from subgroups with early onset, extensive and long-standing inflammation, or primary sclerosing cholangitis the risk of developing colorectal cancer is of th......Ulcerative colitis (UC) is a prevalent inflammatory bowel disease of the colonic mucosa affecting approximately 20,000-25,000 Danes. Apart from subgroups with early onset, extensive and long-standing inflammation, or primary sclerosing cholangitis the risk of developing colorectal cancer...

  15. Bifidobacterium infantis strains with and without a combination of Oligofructose and Inulin (OFI attenuate inflammation in DSS-induced colitis in rats

    Directory of Open Access Journals (Sweden)

    Ahrne Siv

    2006-10-01

    Full Text Available Abstract Background Pathogenesis of inflammatory bowel disease is thought to be through different factors and there is a relationship between the gut flora and the risk of its development. Probiotics can manipulate the microflora in chronic inflammation and may be effective in treating inflammation. Bifidobacterium are saccharolytic and their growth in the gut can be promoted by non-absorbable carbohydrates and its increase in the colon appears to be of benefit. Methods Oligofructose and inulin (OFI alone and the two B. infantis DSM 15158 and DSM 15159 with and without OFI, were fed to Sprague-Dawley rats for 7 days prior to colitis induction and administrations continued for another 7 days with the DSS. Colitis severity assessed using a Disease Activity Index. Samples were collected 7 days after colitis induction, for intestinal bacterial flora, bacterial translocation, short chain fatty acids (SCFAs, myeloperoxidase (MPO, cytokines (IL-1β, TNF-α, IL-10 and TGF-β and malondialdehyde (MDA. Results OFI alone or the B. infantis strains with and without OFI improved significantly the DAI and decreased colonic MPO activity. Colonic tissue IL-1β decreased significantly in all treated groups except B. infantis DSM 15158. MDA decreased significantly in B. infantis DSM 15159 with and without OFI compared to colitis control. Succinic acid increased significantly in OFI group with and without DSM 15159 compared to all groups. Sum values of propionic, succinic acid and butyric acid increased significantly in all groups compare to the colitis control. Bacterial translocation to mesenteric lymph nodes decreased significantly in all groups compared to colitis control. Translocation to the liver decreased significantly in all groups compare to the colitis control and OFI + B. infantis DSM 15158 groups. Conclusion Administrations of OFI and Bifidobacterium improve DSS-induced acute colitis and have an anti-inflammatory effect. Major differences in effect

  16. Berberine ameliorates chronic relapsing dextran sulfate sodium-induced colitis in C57BL/6 mice by suppressing Th17 responses.

    Science.gov (United States)

    Li, Yan-Hong; Xiao, Hai-Tao; Hu, Dong-Dong; Fatima, Sarwat; Lin, Cheng-Yuan; Mu, Huai-Xue; Lee, Nikki P; Bian, Zhao-Xiang

    2016-08-01

    Ulcerative colitis (UC) is an increasingly common condition particularly in developed countries. The lack of satisfactory treatment has fueled the search for alternative therapeutic strategies. In recent studies, berberine, a plant alkaloid with a long history of medicinal use in Chinese medicine, has shown beneficial effects against animal models of acute UC. However, UC usually presents as a chronic condition with frequent relapse in patients. How berberine will act on chronic UC remains unclear. In the present study, we adopted dextran sulfate sodium (DSS)-induced chronic relapsing colitis model to assess the ameliorating activity of berberine. Colitis was induced by two cycles of 2.0% DSS for five days followed by 14days of drinking water plus a third cycle consisting of DSS only for five days. The colitis mice were orally administered 20mg/kg berberine from day 13 onward for 30days and monitored daily. The body weight, stool consistency, and stool bleeding were recorded for determination of the disease activity index (DAI). At the end of treatment, animals were sacrificed and samples were collected and subjected to histological, RT-qPCR, Western blot, and LC-MS analyses. Lymphocytes were isolated from spleens and mesenteric lymph nodes (MLN) and cultured for flow cytometry analysis of IL-17 secretion from CD4(+) cells and the Th17 cell differentiation. Results showed that berberine significantly ameliorated the DAI, colon shortening, colon tissue injury, and reduction of colonic expression of tight junction (TJ) protein ZO-1 and occludin of colitis mice. Notably, berberine treatment pronouncedly reduced DSS-upregulated Th17-related cytokine (IL-17 and ROR-γt) mRNAs in the colon. Furthermore, the mRNA expression of IL-6 and IL-23, and the phosphorylation of STAT3 in colon tissues from DSS-treated mice were pronouncedly inhibited by berberine. Moreover, the up-regulation of IL-17 secretion from CD4(+) cells of spleens and MLNs caused by DSS were significantly

  17. Pyrrolidine Dithiocarbamate Inhibits NF-KappaB Activation and Upregulates the Expression of Gpx1, Gpx4, Occludin, and ZO-1 in DSS-Induced Colitis.

    Science.gov (United States)

    Yin, Jie; Wu, Miaomiao; Duan, Jielin; Liu, Gang; Cui, Zhijie; Zheng, Jie; Chen, Shuai; Ren, Wenkai; Deng, Jinping; Tan, Xiangwen; Al-Dhabi, Naif Abdullah; Duraipandiyan, Veeramuthu; Liao, Peng; Li, Tiejun; Yulong, Yin

    2015-12-01

    Inflammatory bowel disease (IBD) correlates with oxidative stress, inflammation, and alteration in several signal pathways, including nuclear transcription factor-kappaB (NF-κB). Pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-κB, has been widely demonstrated to exhibit an antioxidant and anti-inflammatory function. This study aimed to test the hypothesis that NF-κB inhibitor PDTC confers a beneficial role in a colitis model induced by dextran sodium sulfate (DSS) in mouse. The results showed that DSS decreased daily weight gain, induced colonic inflammation, suppressed the expression of antioxidant enzymes and tight junctions, and activated NF-κB and nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2/Keap1) signaling pathways. PDTC significantly upregulated (P DSS-induced colitis model. Meanwhile, PDTC reversed (P DSS treatment. In conclusion, PDTC could serve as an adjuvant therapy for the patient with IBD.

  18. Enterohemorrhagic Escherichia coli induce attaching and effacing lesions and hemorrhagic colitis in human and bovine intestinal xenograft models

    Directory of Open Access Journals (Sweden)

    Lilach Golan

    2011-01-01

    Enterohemorrhagic Escherichia coli (EHEC O157:H7 is an important cause of diarrhea, hemorrhagic colitis and hemolytic uremic syndrome in humans worldwide. The two major virulence determinants of EHEC are the Shiga toxins (Stx and the type III secretion system (T3SS, including the injected effectors. Lack of a good model system hinders the study of EHEC virulence. Here, we investigated whether bovine and human intestinal xenografts in SCID mice can be useful for studying EHEC and host tissue interactions. Fully developed, germ-free human and bovine small intestine and colon were established by subcutaneous transplantation of human and bovine fetal gut into SCID mice. Xenografts were allowed to develop for 3–4 months and thereafter were infected by direct intraluminal inoculation of Stx-negative derivatives of EHEC O157:H7, strain EDL933. The small intestine and colon xenografts closely mimicked the respective native tissues. Upon infection, EHEC induced formation of typical attaching and effacing lesions and tissue damage that resembled hemorrhagic colitis in colon xenografts. By contrast, xenografts infected with an EHEC mutant deficient in T3SS remained undamaged. Furthermore, EHEC did not attach to or damage the epithelium of small intestinal tissue, and these xenografts remained intact. EHEC damaged the colon in a T3SS-dependent manner, and this model is therefore useful for studying the molecular details of EHEC interactions with live human and bovine intestinal tissue. Furthermore, we demonstrate that Stx and gut microflora are not essential for EHEC virulence in the human gut.

  19. Iron supplementation increases disease activity and vitamin E ameliorates the effect in rats with dextran sulfate sodium-induced colitis.

    Science.gov (United States)

    Carrier, Julie; Aghdassi, Elaheh; Cullen, Jim; Allard, Johane P

    2002-10-01

    Inflammatory bowel disease is often associated with iron deficiency anemia and oral iron supplementation may be required. However, iron may increase oxidative stress through the Fenton reaction and thus exacerbate the disease. This study was designed to determine in rats with dextran sulfate sodium (DSS)-induced colitis whether oral iron supplementation increases intestinal inflammation and oxidative stress and whether the addition of an antioxidant, vitamin E, would reduce this detrimental effect. Four groups of rats that consumed 50 g/L DSS in drinking water were studied for 7 d and were fed: a control, nonpurified diet (iron, 270 mg, and dl-alpha-tocopherol acetate, 49 mg/kg); diet + iron (iron, 3000 mg/kg); diet + vitamin E (dl-alpha-tocopherol acetate, 2000 mg/kg) and the diet + both iron and vitamin E, each at the same concentrations as above. Body weight change, rectal bleeding, histological scores, plasma and colonic lipid peroxides (LPO), plasma 8-isoprostane, colonic glutathione peroxidase (GPx) and plasma vitamin E were measured. Iron supplementation increased disease activity as demonstrated by higher histological scores and heavier rectal bleeding. This was associated with an increase in colonic and plasma LPO and plasma 8-isoprostane as well as a decrease in colonic GPx. Vitamin E supplementation decreased colonic inflammation and rectal bleeding but did not affect oxidative stress, suggesting another mechanism for reducing inflammation. In conclusion, oral iron supplementation resulted in an increase in disease activity in this model of colitis. This detrimental effect on disease activity was reduced by vitamin E. Therefore, the addition of vitamin E to oral iron supplementation may be beneficial. PMID:12368409

  20. Herpes simplex induced necrotizing tonsillitis in an immunocompromised patient with ulcerative colitis.

    Science.gov (United States)

    Jansen, Laura; Vos, Xander G; Löwenberg, Mark

    2016-02-16

    We here present the case of a 22-year-old female of Suriname ethnicity with ulcerative colitis who received treatment with mercaptopurine and infliximab. She presented herself with a severe necrotizing tonsillitis due to herpes simplex virus type-1 (HSV-1). Combination therapy consisting of immunomodulators and anti-tumor necrosis factor (TNF) agents is increasingly being used. Anti-TNF therapy is associated with an increased risk of developing serious infections, and especially patients receiving combination treatment with thiopurines are at an increased risk. We here show that HSV infections can cause a severe tonsillitis in immunocompromised patients. Early recognition is essential when there is no improvement with initial antibiotic therapy within the first 24 to 72 h. HSV infections should be in the differential diagnosis of immunocompromised patients presenting with a necrotizing tonsillitis and can be confirmed by polymerase chain reaction. Early treatment with antiviral agents should be considered especially if antibiotic treatment fails in such patients. PMID:26881193

  1. Citrobacter rodentium-induced colitis: A robust model to study mucosal immune responses in the gut.

    Science.gov (United States)

    Koroleva, Ekaterina P; Halperin, Sydney; Gubernatorova, Ekaterina O; Macho-Fernandez, Elise; Spencer, Cody M; Tumanov, Alexei V

    2015-06-01

    Citrobacter rodentium is a natural mouse pathogen which reproducibly infects mice and causes intestinal disease. The C. rodentium model of infection is very useful for investigating host-pathogen immune interactions in the gut, and can also be used to understand the pathogenesis of several important human intestinal disorders, including Crohn's disease, ulcerative colitis, dysbiosis and colon tumorigenesis. Both innate and adaptive immune responses play a critical role in protection against C. rodentium. Here, we summarize the role of immune components in protection against C. rodentium and describe techniques for the analysis of innate and adaptive mucosal immune responses, including setting up the infection, analysis of colonic hyperplasia and bacterial dissemination, evaluation of antibody responses, and purification and analysis of intestinal epithelial and lymphoid cells.

  2. Mesalizine-Induced Acute Pancreatitis and Interstitial Pneumonitis in a Patient with Ulcerative Colitis.

    Science.gov (United States)

    Chung, Min Jae; Lee, Jae Hee; Moon, Kyung Rye

    2015-12-01

    Ulcerative colitis (UC) is a chronic idiopathic inflammatory bowel disease. Mesalizine for the first-line therapy of UC has adverse effects include pancreatitis, pneumonia and pericarditis. UC complicated by two coexisting conditions, however, is very rare. Moreover, drug-related pulmonary toxicity is particularly rare. An 11-year-old male patient was hospitalized for recurring upper abdominal pain after meals with vomiting, hematochezia and exertional dyspnea developing at 2 weeks of mesalizine therapy for UC. The serum level of lipase was elevated. Chest X-ray and thorax computed tomography showed interstitial pneumonitis. Mesalizine was discontinued and steroid therapy was initiated. Five days after admission, symptoms were resolved and mesalizine was resumed after a drop in amylase and lipase level. Symptoms returned the following day, however, accompanied by increased the serum levels of amylase and lipase. Mesalizine was discontinued again and recurring symptoms rapidly improved.

  3. Hyaluronic acid as a rescue therapy for trinitrobenzene sulfonic acid-induced colitis through Cox-2 and PGE2 in a Toll-like receptor 4-dependent way

    Institute of Scientific and Technical Information of China (English)

    Huan CHEN; Mahesh MAHASETH; Yah ZHANG

    2011-01-01

    We hypothesized whether systemic administration of high-molecular-weight hyaluronic acid (HMW HA) could rescue trinitrobenzene sulfonic acid (TNBS)-induced colitis through Toll-like receptor 4 (TLR4) signal.C3H/HeN mice and C3H/HeJ mice were used.Mice were divided into four groups:control,50% ethanol treatment group,TNBS treatment group,and TNBS plus HA treatment group.The weight changes,clinical scores,macroscopic scores,and histological scores were recorded.Cyclooxygenase 2 (Cox-2) and prostaglandin E2 (PGE2) expressions were measured both in colons and peritoneal macrophages from these mice.HA was a rescue therapy for the colitis induced by TNBS only in C3H/HeN mice.The clinical score,macroscopic score,and histological score were much lower in C3H/HeN mice receiving TNBS plus HA treatment.Cox-2 and PGE2 expressions only increased in C3H/HeN mice.These Cox-2 expressing cells were macrophages.HA can also promote the production of Cox-2 and PGE2 in peritoneal macrophages from C3H/HeN mice.Our data demonstrated that HMW HA can rescue TNBS-induced colitis through inducing Cox-2 and PGE2 expressions in a TLR4-dependent way.Macrophages may be the effector cells of HMW HA.

  4. CMV - gastroenteritis/colitis

    Science.gov (United States)

    Colitis - cytomegalovirus; Gastroenteritis - cytomegalovirus; Gastrointestinal CMV disease ... or after bone marrow or organ transplant Ulcerative colitis or Crohn disease Rarely, serious CMV infection involving ...

  5. Calcitriol analog ZK191784 ameliorates acute and chronic dextran sodium sulfate-induced colitis by modulation of intestinal dendritic cell numbers and phenotype

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To investigate the effects of ZK1916784, a low calcemic analog of calcitriol on intestinal inflammation.METHODS: Acute and chronic colitis was induced by dextran sodium sulfate (DSS) according to standard procedures. Mice were treated intraperitoneally with ZK1916784 or placebo and colonic inflammation was evaluated. Cytokine production by mesenterial lymph node (MLN) cells was measured by ELISA.Immunohistochemistry was performed to detect intestinal dendritic cells (DCs) within the colonic tissue,and the effect of the calcitriol analog on DCs was investigated.RESULTS: Treatment with ZK191784 resulted in significant amelioration of disease with a reduced histological score in acute and chronic intestinal inflammation. In animals with acute DSS colitis, down-regulation of colonic inflammation was associated with a dramatic reduction in the secretion of the proinflammatory cytokine interferon (IFN)-γ and a significant increase in intereleukin (IL)-10 by MLN cells.Similarly, in chronic colitis, IL-10 expression in colonic tissue increased 1.4-fold when mice were treated with ZK191784, whereas expression of the Th1-specific transcription factor T-beta decreased by 81.6%. Lower numbers of infiltrating activated CD11c+ DCs were found in the colon in ZK191784-treated mice with acute DSS colitis, and secretion of proinflammatory cytokines by primary mucosal DCs was inhibited in the presence of the calcitriol analog.CONCLUSION: The calcitriol analog ZK191784 demonstrated significant anti-inflammatory properties in experimental colitis that were at least partially mediated by the immunosuppressive effects of the derivate on mucosal DCs.

  6. Dietary vitamin D3 deficiency alters intestinal mucosal defense and increases susceptibility to Citrobacter rodentium-induced colitis.

    Science.gov (United States)

    Ryz, Natasha R; Lochner, Arion; Bhullar, Kirandeep; Ma, Caixia; Huang, Tina; Bhinder, Ganive; Bosman, Else; Wu, Xiujuan; Innis, Sheila M; Jacobson, Kevan; Vallance, Bruce A

    2015-11-01

    Vitamin D deficiency affects more that 1 billion people worldwide. Although thought to increase risk of bacterial infections, the importance of vitamin D on host defense against intestinal bacterial pathogens is currently unclear since injection of the active form of vitamin D, 1,25(OH)2D3, increased susceptibility to the enteric bacterial pathogen Citrobacter rodentium by suppressing key immune/inflammatory factors. To further characterize the role of vitamin D during bacteria-induced colitis, we fed weanling mice either vitamin D3-deficient or vitamin D3-sufficient diets for 5 wk and then challenged them with C. rodentium. Vitamin D3-deficient mice lost significantly more body weight, carried higher C. rodentium burdens, and developed worsened histological damage. Vitamin D3-deficient mice also suffered greater bacterial translocation to extra-intestinal tissues, including mesenteric lymph nodes, spleen, and liver. Intestinal tissues of infected vitamin D3-deficient mice displayed increased inflammatory cell infiltrates as well as significantly higher gene transcript levels of inflammatory mediators TNF-α, IL-1β, IL-6, TGF-β, IL-17A, and IL-17F as well as the antimicrobial peptide REG3γ. Notably, these exaggerated inflammatory responses accelerated the loss of commensal microbes and were associated with an impaired ability to detoxify bacterial lipopolysaccharide. Overall, these studies show that dietary-induced vitamin D deficiency exacerbates intestinal inflammatory responses to infection, also impairing host defense.

  7. Protective Effect of Dietary Lily Bulb on Dextran Sulfate Sodium-Induced Colitis in Rats Fed a High-Fat Diet.

    Science.gov (United States)

    Okazaki, Yukako; Chiji, Hideyuki; Kato, Norihisa

    2016-01-01

    Lily bulb is traditionally consumed in East Asia and contains high amounts of glucomannan. This study investigated the effect of dietary lily bulb on dextran sulfate sodium (DSS)-induced colitis in rats fed a high-fat (HF) diet. Male Sprague-Dawley rats were fed a diet containing 30% beef tallow with or without 7% steamed lily bulb powder for 17 d. Experimental colitis was induced by replacing drinking water with DSS during the last 7 d. The disease activity index (DAI) was significantly lower in the lily bulb+DSS group than in the DSS group on day 17. The fecal abundance of Bifidobacterium was significantly reduced in the DSS group compared with that in the control group, but it was recovered by lily bulb intake. Cecal butyrate, fecal mucins, and alkaline phosphatase (ALP) activity were significantly higher in the DSS group than in the control group. Dietary lily bulb potentiated the increase in cecal butyrate, fecal mucins, and the ALP activity caused by DSS treatment. These results indicate that lily bulb attenuates DSS-induced colitis by modulating colonic microflora, organic acids, mucins, and ALP activity in HF diet-fed rats. PMID:27465728

  8. The cell surface receptor Slamf6 modulates innate immune responses during Citrobacter rodentium-induced colitis.

    Science.gov (United States)

    van Driel, Boaz; Wang, Guoxing; Liao, Gongxian; Halibozek, Peter J; Keszei, Marton; O'Keeffe, Michael S; Bhan, Atul K; Wang, Ninghai; Terhorst, Cox

    2015-09-01

    The homophilic cell surface receptors CD150 (Slamf1) and CD352 (Slamf6) are known to modulate adaptive immune responses. Although the Th17 response was enhanced in Slamf6(-/-) C57BL/6 mice upon oral infection with Citrobacter rodentium, the pathologic consequences are indistinguishable from an infection of wild-type C57BL/6 mice. Using a reporter-based binding assay, we show that Slamf6 can engage structures on the outer cell membrane of several Gram(-) bacteria. Therefore, we examined whether Slamf6, like Slamf1, is also involved in innate responses to bacteria and regulates peripheral inflammation by assessing the outcome of C. rodentium infections in Rag(-/-) mice. Surprisingly, the pathology and immune responses in the lamina propria of C. rodentium-infected Slamf6(-/-) Rag(-/-) mice were markedly reduced as compared with those of Rag(-/-) mice. Infiltration of inflammatory phagocytes into the lamina propria was consistently lower in Slamf6(-/-) Rag(-/-) mice than in Rag(-/-) animals. Concomitant with the reduced systemic translocation of the bacteria was an enhanced production of IL-22, suggesting that Slamf6 suppresses a mucosal protective program. Furthermore, administering a mAb (330) that inhibits bacterial interactions with Slamf6 to Rag(-/-) mice ameliorated the infection compared with a control antibody. We conclude that Slamf6-mediated interactions of colonic innate immune cells with specific Gram(-) bacteria reduce mucosal protection and enhance inflammation, contributing to lethal colitis that is caused by C. rodentium infections in Rag(-/-) mice.

  9. Selenoprotein P influences colitis-induced tumorigenesis by mediating stemness and oxidative damage

    Science.gov (United States)

    Barrett, Caitlyn W.; Reddy, Vishruth K.; Short, Sarah P.; Motley, Amy K.; Lintel, Mary K.; Bradley, Amber M.; Freeman, Tanner; Vallance, Jefferson; Ning, Wei; Parang, Bobak; Poindexter, Shenika V.; Fingleton, Barbara; Chen, Xi; Washington, Mary K.; Wilson, Keith T.; Shroyer, Noah F.; Hill, Kristina E.; Burk, Raymond F.; Williams, Christopher S.

    2015-01-01

    Patients with inflammatory bowel disease are at increased risk for colon cancer due to augmented oxidative stress. These patients also have compromised antioxidant defenses as the result of nutritional deficiencies. The micronutrient selenium is essential for selenoprotein production and is transported from the liver to target tissues via selenoprotein P (SEPP1). Target tissues also produce SEPP1, which is thought to possess an endogenous antioxidant function. Here, we have shown that mice with Sepp1 haploinsufficiency or mutations that disrupt either the selenium transport or the enzymatic domain of SEPP1 exhibit increased colitis-associated carcinogenesis as the result of increased genomic instability and promotion of a protumorigenic microenvironment. Reduced SEPP1 function markedly increased M2-polarized macrophages, indicating a role for SEPP1 in macrophage polarization and immune function. Furthermore, compared with partial loss, complete loss of SEPP1 substantially reduced tumor burden, in part due to increased apoptosis. Using intestinal organoid cultures, we found that, compared with those from WT animals, Sepp1-null cultures display increased stem cell characteristics that are coupled with increased ROS production, DNA damage, proliferation, decreased cell survival, and modulation of WNT signaling in response to H2O2-mediated oxidative stress. Together, these data demonstrate that SEPP1 influences inflammatory tumorigenesis by affecting genomic stability, the inflammatory microenvironment, and epithelial stem cell functions. PMID:26053663

  10. Aquaporin-8 expression is reduced in ileum and induced in colon of patients with ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Alexandra Zahn; Christoph Moehle; Thomas Langmann; Robert Ehehalt; Frank Autschbach; Wolfgang Stremmel; Gerd Schmitz

    2007-01-01

    AIM: To study susceptibility genes which may play a potential role in the pathogenesis and etiology of inflammatory bowel disease (IBD).METHODS: To identify potential susceptibility genes we performed global gene expression profiling in patients with IBD and control specimens. For determination of an intrinsic gene expression profile in ulcerative colitis (UC) and Crohn's disease (CD) compared to normal subjects, mucosal biopsies of non-inflamed regions of the colon and the terminal ileum were subjected to DNA microarray analysis. Real-time RT-PCR and immunohistochemistry were used for verification of selected regulated candidate genes and a genetic analysis was performed.RESULTS: We could show that aquaporin-8 (AQP8) mRNA and protein levels were significantly increased in the colon of UC patients compared to controls. Genetic analysis of the six exons and the promoter region of AQP8, however, revealed no mutations or polymorphisms in IBD patients.CONCLUSION: Our results suggest that upregulation of AQP8 in the colon of UC patients represents a secondary phenomenon which may, due to altered water exchange of the distal intestinal mucosa, disturb the physiologic colonic mucus barrier and thus lead to chronic inflammation and ulceration.

  11. MALT1 inhibitors prevent the development of DSS-induced experimental colitis in mice via inhibiting NF-κB and NLRP3 inflammasome activation.

    Science.gov (United States)

    Liu, Wen; Guo, Wenjie; Hang, Nan; Yang, Yuanyuan; Wu, Xuefeng; Shen, Yan; Cao, Jingsong; Sun, Yang; Xu, Qiang

    2016-05-24

    Mucosa-associated-lymphoid-tissue lymphoma-translocation gene 1 (MALT1), a paracaspase and essential regulator for nuclear factor kB (NF-κB) activation, plays an important role in innate and adaptive immunity. Suppression of MALT1 protease activity with small molecule inhibitors showed promising efficacies in subtypes of B cell lymphoma and improvement in experimental autoimmune encephalomyelitis model. However, whether MALT1 inhibitors could ameliorate colitis remains unclear. In the present study, we examined the pharmacological effect of two specific MALT1 inhibitors MI-2 and mepazine on the dextran sulfate sodium (DSS)-induced experimental colitis in mice, followed by mechanistic analysis on NF-κB and NLRP3 inflammasome activation. Treatment with MI-2 and mepazine dose-dependently attenuated symptoms of colitis in mice, evidenced by reduction in the elevated disease activity index, the shortening of colon length as well as the histopathologic improvement. Moreover, protein and mRNA levels of DSS-induced proinflammatory cytokines in colon, including TNF, IL-1β, IL-6, IL-18, IL-17A and IFN-γ, were markedly suppressed by MALT1 inhibitors. The underlying mechanisms for the protective effect of MALT1 inhibitors in DSS-induced colitis may be attributed to its inhibition on NF-κB and NLRP3 inflammasome activation in macrophages. The in vitro study showed that MALT1 inhibitors decreased production of IL-1β/IL-18 in phorbol myristate acetate-differentiated THP-1 cells and bone marrow derived macrophage via suppressing the activation of NF-κB and NLRP3 inflammasome. Taken together, our results demonstrated that inhibition of the protease activity of MALT1 might be a viable strategy to treat inflammatory bowel disease and the NLRP3 inflammasome and NF-κB activation are critical components in MALT1 signaling cascades in this disease model.

  12. The impact of JNK inhibitor D-JNKI-1 in a murine model of chronic colitis induced by dextran sulfate sodium

    Directory of Open Access Journals (Sweden)

    Kersting S

    2013-05-01

    Full Text Available Sabine Kersting,1* Volker Behrendt,1* Jonas Kersting,1 Kirstin Reinecke,3 Christoph Hilgert,1 Ingo Stricker,2 Thomas Herdegen,3 Monika S Janot,1 Waldemar Uhl,1 Ansgar M Chromik1 1Department of General and Visceral Surgery, St Josef Hospital, Ruhr University of Bochum, Bochum, Germany; 2Department of Pathology, Ruhr University of Bochum, Bochum, Germany; 3Institute of Experimental and Clinical Pharmacology, University Hospital of Schleswig-Holstein, Kiel, Germany *The two authors Sabine Kersting and Volker Behrendt contributed equally to this work Purpose: The c-Jun N-terminal kinases (JNK are involved in the activation of T cells and the synthesis of proinflammatory cytokines. Several studies have established the relevance of the JNK pathway in inflammatory bowel diseases. The present study analyzed the therapeutic effect of D-JNKI-1, a specific JNK-inhibiting peptide, in a low-dose dextran sulfate sodium (DSS model of chronic colitis. Methods: DSS colitis was induced in female C57/BL6 mice by cyclic administration using different concentrations of DSS (1.0% and 1.5%. Mice in the intervention groups received subcutaneous administration of 1 µg/kg D-JNKI-1 on days 2, 12, and 22. They were monitored daily to assess the severity of colitis, body weight, stool consistency, and the occurrence of occult blood or gross rectal bleeding using evaluation of the disease activity index. The animals were sacrificed after 30 days, and the inflamed intestine was histologically evaluated using a crypt damage score. Immunohistochemical quantification of CD4+ and CD8+ cells was also carried out. Results: Administration of 1 µg/kg D-JNKI-1 resulted in a significant decrease in the disease activity index (P = 0.013 for 1.0% DSS; P = 0.007 for 1.5% DSS. As a mild form of colitis was induced, histological examination did not show any distinct damage to the mucosa and crypts. However, expression of CD4+ and CD8+ cells was reduced in mice treated with D-JNKI-1 (not

  13. DSS colitis promotes tumorigenesis and fibrogenesis in a choline-deficient high-fat diet-induced NASH mouse model.

    Science.gov (United States)

    Achiwa, Koichi; Ishigami, Masatoshi; Ishizu, Yoji; Kuzuya, Teiji; Honda, Takashi; Hayashi, Kazuhiko; Hirooka, Yoshiki; Katano, Yoshiaki; Goto, Hidemi

    2016-01-29

    Nonalcoholic steatohepatitis (NASH) patients progress to liver cirrhosis and even hepatocellular carcinoma (HCC). Several lines of evidence indicate that accumulation of lipopolysaccharide (LPS) and disruption of gut microbiota play contributory roles in HCC. Moreover, in a dextran sodium sulfate (DSS)-induced colitis model in mice, a high-fat diet increases portal LPS level and promotes hepatic inflammation and fibrosis. However, this diet-induced NASH model requires at least 50 weeks for carcinogenesis. In this study, we sought to determine whether increased intestinal permeability would aggravate liver inflammation and fibrosis and accelerate tumorigenesis in a diet-induced NASH model. Mice were fed a choline-deficient high-fat (CDHF) diet for 4 or 12 weeks. The DSS group was fed CDHF and intermittently received 1% DSS in the drinking water. Exposure to DSS promoted mucosal changes such as crypt loss and increased the number of inflammatory cells in the colon. In the DSS group, portal LPS levels were elevated at 4 weeks, and the proportions of Clostridium cluster XI in the fecal microbiota were elevated. In addition, levels of serum transaminase, number of lobular inflammatory cells, F4/80 staining-positive area, and levels of inflammatory cytokines were all elevated in the DSS group. Liver histology in the DSS group revealed severe fibrosis at 12 weeks. Liver tumors were detected in the DSS group at 12 weeks, but not in the other groups. Thus, DSS administration promoted liver tumors in a CDHF diet-induced NASH mouse over the short term, suggesting that the induction of intestinal inflammation and gut disruption of microbiota in NASH promote hepatic tumorigenesis.

  14. Diallyl Disulfide (DADS), a Constituent of Garlic, Inactivates NF-κB and Prevents Colitis-Induced Colorectal Cancer by Inhibiting GSK-3β.

    Science.gov (United States)

    Saud, Shakir M; Li, Weidong; Gray, Zane; Matter, Matthias S; Colburn, Nancy H; Young, Matthew R; Kim, Young S

    2016-07-01

    There is a strong belief that garlic has medicinal properties and may even reduce the risk of developing certain cancers including those of the gastrointestinal tract. The chemopreventive effects of garlic may be attributed to the anti-inflammatory properties of the sulfur-containing constituents of garlic, which includes diallyl disulfide (DADS). Here, we demonstrate that DADS prevented colorectal tumorigenesis in a mouse model of colitis-induced colorectal cancer. Supplementation with 85 ppm of DADS (60 mg daily human equivalent dose) in the diet of FVB/N mice treated with chemical carcinogen azoxymethane (AOM) and colonic irritant dextran sodium sulfate (DSS) resulted in the reduction in tumor incidence, tumor number, and tumor burden by 21.54%, 47.3%, and 66.4%, respectively. Further analysis revealed that mice fed the DADS-supplemented diet resolved the initial DSS-induced inflammation faster than those on the control diet, preventing prolonged inflammation and cellular transformation. Subsequent mechanistic studies in vitro suggest that DADS chemopreventive effects are mediated through NF-κB signaling. When SW480 colorectal cancer cells were treated with DADS, NF-κB nuclear localization and activity were diminished. Interestingly, NF-κB suppression was found to be dependent on DADS inhibition of GSK-3β, a positive regulator of NF-κB. Inhibition of GSK-3β and loss of nuclear NF-κB activity were also observed in vivo in AOM/DSS-treated mice fed a diet supplemented with 85 ppm DADS. Our results indicate that DADS can prevent tumorigenesis by suppressing inflammation, a process largely involving GSK-3β inhibition and consequential reduction in NF-κB nuclear localization. Cancer Prev Res; 9(7); 607-15. ©2016 AACR. PMID:27138790

  15. Regulation of the alternative pathway of complement modulates injury and immunity in a chronic model of dextran sulphate sodium-induced colitis

    Science.gov (United States)

    Elvington, M; Schepp-Berglind, J; Tomlinson, S

    2015-01-01

    The role of complement in inflammatory bowel disease (IBD) has been studied primarily using acute models, and it is unclear how complement affects processes in more relevant chronic models of IBD in which modulation of adaptive immunity and development of fibrosis have pathogenic roles. Using mice deficient in C1q/mannose-binding lectin (MBL) or C3, we demonstrated an important role for these opsonins and/or the classical pathway C3 convertase in providing protection against mucosal injury and infection in a model of chronic dextran sulphate sodium (DSS)-induced colitis. In contrast, deficiency of the alternative pathway (fB–/– mice) had significantly less impact on injury profiles. Consequently, the effect of a targeted inhibitor of the alternative pathway was investigated in a therapeutic protocol. Following the establishment of colitis, mice were treated with CR2-fH during subsequent periods of DSS treatment and acute injury (modelling relapse). CR2-fH significantly reduced complement activation, inflammation and injury in the colon, and additionally reduced fibrosis. Alternative pathway inhibition also altered the immune response in the chronic state in terms of reducing numbers of B cells, macrophages and mature dendritic cells in the lamina propria. This study indicates an important role for the alternative pathway of complement in the pathogenesis and the shaping of an immune response in chronic DSS-induced colitis, and supports further investigation into the use of targeted alternative pathway inhibition for the treatment of IBD. PMID:25293413

  16. Bimatoprost-induced chemical blepharoplasty.

    Science.gov (United States)

    Sarnoff, Deborah S; Gotkin, Robert H

    2015-05-01

    We report significant changes in the appearance of the periorbital area, beyond eyelash enhancement, induced by the topical application of bimatoprost ophthalmic solution, 0.03% (Latisse®, Allergan, Inc., Irvine, CA). To our knowledge, this is the first report in the dermatology or plastic surgery literature describing the rejuvenating effect and overall improvement in the appearance of the periorbital area resulting from applying Latisse to the upper eyelid margins. To date, reports in the literature discuss side-effects and potential complications of topical bimatoprost therapy causing a constellation of findings known as PAP (prostaglandin-associated periorbitopathy). While periorbitopathy implies pathology or a state of disease, we report changes that can be perceived as an improvement in the overall appearance of the periorbital area. We, therefore, propose a name change from PAP to PAPS - prostaglandin- associated periorbital syndrome. This better describes the beneficial, as well as the possible negative effects of topical bimatoprost. Although there is a risk for periorbital disfigurement, when used bilaterally, in properly selected candidates and titrated appropriately, bimatoprost can be beneficial. The striking improvement in the appearance of some individuals warrants further research into the potential use of topical bimatoprost to achieve a "chemical blepharoplasty."

  17. Oroxyloside prevents dextran sulfate sodium-induced experimental colitis in mice by inhibiting NF-κB pathway through PPARγ activation.

    Science.gov (United States)

    Wang, Xiaoping; Sun, Yang; Zhao, Yue; Ding, Youxiang; Zhang, Xiaobo; Kong, Lingyi; Li, Zhiyu; Guo, Qinglong; Zhao, Li

    2016-04-15

    Oroxyloside, as a metabolite of oroxylin A, may harbor various beneficial bioactivities which have rarely been reported in the previous studies. Here we established the dextran sulfate sodium (DSS)-induced experimental colitis and evaluated the anti-inflammatory effect of oroxyloside in vivo. As a result, oroxyloside attenuated DSS-induced body weight loss, colon length shortening and colonic pathological damage. Furthermore, oroxyloside inhibited inflammatory cell infiltration and decreased myeloperoxidase (MPO) and inducible nitric oxide synthase (iNOS) activities as well. The production of pro-inflammatory cytokines in serum and colon was also significantly reduced by oroxyloside. We unraveled the underlying mechanisms that oroxyloside inhibited NF-κB pathway by activating Peroxisome Proliferator-Activated Receptor γ (PPARγ) to attenuate DSS-induced colitis. Moreover, we investigated the anti-inflammatory effect and mechanisms of oroxyloside in the mouse macrophage cell line RAW264.7 and bone marrow derived macrophages (BMDM). Oroxyloside decreased several LPS-induced inflammatory cytokines, including IL-1β, IL-6 and TNF-α in RAW264.7 and BMDM. We also found that oroxyloside inhibited LPS-induced activation of NF-κB signaling pathway via activating PPARγ in RAW 264.7 and BMDM. Docking study showed that oroxyloside could bind with PPARγ. GW9662, the inhibitor of PPARγ, and PPARγ siRNA transfection blocked the effect of oroxyloside on PPARγ activation. Our study suggested that oroxyloside prevented DSS-induced colitis by inhibiting NF-κB pathway through PPARγ activation. Therefore, oroxyloside may be a promising and effective agent for inflammatory bowel disease (IBD).

  18. Effects of dietary virgin olive oil polyphenols: hydroxytyrosyl acetate and 3, 4-dihydroxyphenylglycol on DSS-induced acute colitis in mice.

    Science.gov (United States)

    Sánchez-Fidalgo, Susana; Villegas, Isabel; Aparicio-Soto, Marina; Cárdeno, Ana; Rosillo, Ma Ángeles; González-Benjumea, Alejandro; Marset, Azucena; López, Óscar; Maya, Inés; Fernández-Bolaños, José G; Alarcón de la Lastra, Catalina

    2015-05-01

    Hydroxytyrosol, a polyphenolic compound from extra virgin olive oil (EVOO) has exhibited an improvement in a model of DSS-induced colitis. However, other phenolic compounds present such as hydroxytyrosyl acetate (HTy-Ac) and 3,4-dihydroxyphenylglycol (DHPG) need to be explored to complete the understanding of the overall effects of EVOO on inflammatory colon mucosa. This study was designed to evaluate the effect of both HTy-Ac and DHPG dietary supplementation in the inflammatory response associated to colitis model. Six-week-old mice were randomized in four dietary groups: sham and control groups received standard diet, and other two groups were fed with HTy-Ac and DHPG, respectively, at 0.1%. After 30 days, all groups except sham received 3% DSS in drinking water for 5 days followed by a regime of 5 days of water. Acute inflammation was evaluated by Disease Activity Index (DAI), histology and myeloperoxidase (MPO) activity. Colonic expression of iNOS, COX-2, MAPKs, NF-kB and FOXP3 were determined by western blotting. Only HTy-Ac-supplemented group showed a significant DAI reduction as well as an improvement of histological damage and MPO. COX-2 and iNOS protein expression were also significantly reduced. In addition, this dietary group down-regulated JNK phosphorylation and prevented the DSS-induced nuclear translocation level of p65. However, no significant differences were observed in the FOXP3 expression. These results demonstrated, for the first time, that HTy-Ac exerts an antiinflammatory effect on acute ulcerative colitis. We concluded that HTy-Ac supplement might provide a basis for developing a new dietary strategy for the prevention of ulcerative colitis.

  19. mTOR Inhibition Attenuates Dextran Sulfate Sodium-Induced Colitis by Suppressing T Cell Proliferation and Balancing TH1/TH17/Treg Profile.

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    Shurong Hu

    Full Text Available It has been established that mammalian target of Rapamycin (mTOR inhibitors have anti-inflammatory effects in models of experimental colitis. However, the underlying mechanism is largely unknown. In this research, we investigate the anti-inflammatory effects of AZD8055, a potent mTOR inhibitor, on T cell response in dextran sulfate sodium (DSS-induced colitis in mice, a commonly used animal model of inflammatory bowel diseases (IBD. Severity of colitis is evaluated by changing of body weight, bloody stool, fecal consistency, histology evaluation and cytokine expression. We find that AZD8055 treatment attenuates DSS-induced body weight loss, colon length shortening and pathological damage of the colon. And AZD8055 treatment decreases colonic expression of genes encoding the pro-inflammatory cytokines interferon-γ, interleukin (IL-17A, IL-1β,IL-6 and tumor necrosis factor(TNF-a and increases colonic expression of anti-inflammatory cytokines IL-10. We show that AZD8055 treatment decreases the percentages of CD4+ T cells and CD8+ T cells in spleen, lymph nodes and peripheral blood of mice. We also find that AZD8055 treatment significantly reduces the number of T helper 1(TH1 cells and TH17 cells and increases regulatory T (Treg cells in the lamina propria and mesenteric lymph nodes. Furthermore, we demonstrates that AZD8055 suppresses the proliferation of CD4+ and CD8+ T cells and the differentiation of TH1/TH17 cells and expands Treg cells in vitro. The results suggest that, in experimental colitis, AZD8055 exerts anti-inflammatory effect by regulating T helper cell polarization and proliferation.

  20. Extracellular vesicles derived from gut microbiota, especially Akkermansia muciniphila, protect the progression of dextran sulfate sodium-induced colitis.

    Science.gov (United States)

    Kang, Chil-Sung; Ban, Mingi; Choi, Eun-Jeong; Moon, Hyung-Geun; Jeon, Jun-Sung; Kim, Dae-Kyum; Park, Soo-Kyung; Jeon, Seong Gyu; Roh, Tae-Young; Myung, Seung-Jae; Gho, Yong Song; Kim, Jae Gyu; Kim, Yoon-Keun

    2013-01-01

    Gut microbiota play an important part in the pathogenesis of mucosal inflammation, such as inflammatory bowel disease (IBD). However, owing to the complexity of the gut microbiota, our understanding of the roles of commensal and pathogenic bacteria in the maintenance of immune homeostasis in the gut is evolving only slowly. Here, we evaluated the role of gut microbiota and their secreting extracellular vesicles (EV) in the development of mucosal inflammation in the gut. Experimental IBD model was established by oral application of dextran sulfate sodium (DSS) to C57BL/6 mice. The composition of gut microbiota and bacteria-derived EV in stools was evaluated by metagenome sequencing using bacterial common primer of 16S rDNA. Metagenomics in the IBD mouse model showed that the change in stool EV composition was more drastic, compared to the change of bacterial composition. Oral DSS application decreased the composition of EV from Akkermansia muciniphila and Bacteroides acidifaciens in stools, whereas increased EV from TM7 phylum, especially from species DQ777900_s and AJ400239_s. In vitro pretreatment of A. muciniphila-derived EV ameliorated the production of a pro-inflammatory cytokine IL-6 from colon epithelial cells induced by Escherichia coli EV. Additionally, oral application of A. muciniphila EV also protected DSS-induced IBD phenotypes, such as body weight loss, colon length, and inflammatory cell infiltration of colon wall. Our data provides insight into the role of gut microbiota-derived EV in regulation of intestinal immunity and homeostasis, and A. muciniphila-derived EV have protective effects in the development of DSS-induced colitis. PMID:24204633

  1. Extracellular vesicles derived from gut microbiota, especially Akkermansia muciniphila, protect the progression of dextran sulfate sodium-induced colitis.

    Directory of Open Access Journals (Sweden)

    Chil-Sung Kang

    Full Text Available Gut microbiota play an important part in the pathogenesis of mucosal inflammation, such as inflammatory bowel disease (IBD. However, owing to the complexity of the gut microbiota, our understanding of the roles of commensal and pathogenic bacteria in the maintenance of immune homeostasis in the gut is evolving only slowly. Here, we evaluated the role of gut microbiota and their secreting extracellular vesicles (EV in the development of mucosal inflammation in the gut. Experimental IBD model was established by oral application of dextran sulfate sodium (DSS to C57BL/6 mice. The composition of gut microbiota and bacteria-derived EV in stools was evaluated by metagenome sequencing using bacterial common primer of 16S rDNA. Metagenomics in the IBD mouse model showed that the change in stool EV composition was more drastic, compared to the change of bacterial composition. Oral DSS application decreased the composition of EV from Akkermansia muciniphila and Bacteroides acidifaciens in stools, whereas increased EV from TM7 phylum, especially from species DQ777900_s and AJ400239_s. In vitro pretreatment of A. muciniphila-derived EV ameliorated the production of a pro-inflammatory cytokine IL-6 from colon epithelial cells induced by Escherichia coli EV. Additionally, oral application of A. muciniphila EV also protected DSS-induced IBD phenotypes, such as body weight loss, colon length, and inflammatory cell infiltration of colon wall. Our data provides insight into the role of gut microbiota-derived EV in regulation of intestinal immunity and homeostasis, and A. muciniphila-derived EV have protective effects in the development of DSS-induced colitis.

  2. Mulberry fruit prevents LPS-induced NF-κB/pERK/MAPK signals in macrophages and suppresses acute colitis and colorectal tumorigenesis in mice.

    Science.gov (United States)

    Qian, Zhengjiang; Wu, Zhiqin; Huang, Lian; Qiu, Huiling; Wang, Liyan; Li, Li; Yao, Lijun; Kang, Kang; Qu, Junle; Wu, Yonghou; Luo, Jun; Liu, Johnson J; Yang, Yi; Yang, Wancai; Gou, Deming

    2015-11-30

    Here, we investigated the impact of mulberry fruit (MBF) extracts on lipopolysaccharide (LPS)-induced inflammatory responses in RAW 264.7 macrophages, and the therapeutic efficacy of MBF diet in mice with dextran sulfate sodium (DSS)-induced acute colitis and MUC2(-/-) mice with colorectal cancer. In vitro, LPS-induced nitric oxide (NO) production was significantly inhibited by MBF extracts via suppressing the expression of proinflammatory molecules, including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-1 beta (IL-β) and IL-6. Particularly, a dose-dependent inhibition on LPS-induced inflammatory responses was observed following treatment with MBF dichloromethane extract (MBF-DE), in which linoleic acid and ethyl linolenate were identified as two active compounds. Moreover, we elucidated that MBF-DE attenuated LPS-induced inflammatory responses by blocking activation of both NF-κB/p65 and pERK/MAPK pathways. In vivo, DSS-induced acute colitis was significantly ameliorated in MBF-fed mice as gauged by weight loss, colon morphology and histological damage. In addition, MBF-fed MUC2(-/-) mice displayed significant decrease in intestinal tumor and inflammation incidence compared to control diet-fed group. Overall, our results demonstrated that MBF suppressed the development of intestinal inflammation and tumorgenesis both in vitro and in vivo, and supports the potential of MBF as a therapeutic functional food for testing in human clinical trials.

  3. Treatment with novel AP-1 and NF-κB inhibitors restores the colonic endocrine cells to normal levels in rats with DSS-induced colitis.

    Science.gov (United States)

    El-Salhy, Magdy; Umezawa, Kazuo

    2016-03-01

    The aim of this study was to determine the effects of two anti-inflammatory agents on the abnormalities in colonic endocrine cells in dextran sodium sulfate (DSS)-induced colitis. Colitis was induced in male Wistar rats (n=45) using DSS; a further 15 rats without colitis were included in a healthy control group. The animals with DSS-induced colitis were randomly divided into 3 treatment groups as follows: i) DSS group, rats were treated with 0.5 ml of 0.5% carboxymethyl cellulose (CMC); ii) DSS‑G group, rats were treated with 3-[(dodecylthiocarbonyl)‑methyl]‑glutarimide (DTCM‑G), a novel activator protein 1 (AP-1) inhibitor, 20 mg/kg in CMC; and iii) DSS‑Q group, rats were treated with dehydroxymethylepoxyquinomicin, a nuclear factor κB (NF-κB) inhibitor, 15 mg/kg in CMC. The treatments were administered intraperitoneally, twice daily for 5 days, after which the animals were sacrificed and tissue samples from the colon were immunostained for chromogranin A (CgA), serotonin, peptide YY (PYY), enteroglucagon, pancreatic polypeptide (PP), somatostatin, leukocytes, B/T lymphocytes, B lymphocytes, T lymphocytes, macrophages/monocytes and mast cells. The densities of these endocrine and immune cells were quantified by computer‑aided image analysis. The densities of CgA-, serotonin-, PYY- and enteroglucagon-producing cells were significantly higher, and those of PP- and somatostatin-producing cells were significantly lower in the DSS‑G, DSS‑Q and control groups than in the DSS group. The densities of all the immune cells were lower in the DSS‑G, DSS‑Q and control groups than in the DSS group. The densities of all endocrine cell types and immune cells in both the DSS groups treated with anti‑inflammatory agents were restored to control levels. In conclusion, our data demonstrate that there is an interaction between endocrine and immune cells during inflammation. This interaction with subsequent changes in endocrine cells is responsible for the

  4. Nod2 activates NF-kB in CD4+ T cells but its expression is dispensable for T cell-induced colitis.

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    Galliano Zanello

    Full Text Available Although the etiology of Crohn's disease (CD remains elusive this disease is characterized by T cell activation that leads to chronic inflammation and mucosal damage. A potential role for maladaptation between the intestinal microbiota and the mucosal immune response is suggested by the fact that mutations in the pattern recognition receptor Nod2 are associated with higher risks for developing CD. Although Nod2 deletion in CD4(+ T cells has been shown to impair the induction of colitis in the murine T cell transfer model, the analysis of T cell intrinsic Nod2 function in T cell differentiation and T cell-mediated immunity is inconsistent between several studies. In addition, the role of T cell intrinsic Nod2 in regulatory T cell (Treg development and function during colitis remain to be analyzed. In this study, we show that Nod2 expression is higher in activated/memory CD4(+ T cells and its expression was inducible after T cell receptor (TCR ligation. Nod2 stimulation with muramyl dipeptide (MDP led to a nuclear accumulation of c-Rel NF-kB subunit. Although functionally active in CD4(+ T cells, the deletion of Nod2 did not impair the induction and the prevention of colitis in the T cell transfer model. Moreover, Nod2 deletion did not affect the development of Foxp3(+ Treg cells in the spleen of recipient mice and Nod2 deficient CD4 T cells expressing the OVA specific transgenic TCR were able to differentiate in Foxp3(+ Treg cells after OVA feeding. In vitro, CD25(+ Nod2 deficient T cells suppressed T cell proliferation as well as wild type counter parts and T cell stimulation with MDP did not affect the proliferation and the cytokine secretion of T cells. In conclusion, our data indicate that Nod2 is functional in murine CD4(+ T cells but its expression is dispensable for the T cell regulation of colitis.

  5. Anti-Saccharomyces cerevisiae antibody titers are stable over time in Crohn's patients and are not inducible in murine models of colitis

    Institute of Scientific and Technical Information of China (English)

    Stefan Müller; Maya Styner; Beatrice Seibold-Schmid; Beatrice Flogerzi; Michael M(a)hler; Astrid Konrad; Frank Seibold

    2005-01-01

    AIM: To investigate ASCA production over time in CD and murine colitis in order to further our understanding of their etiology.MATERIALS AND METHODS: Sixty-six CD patients were compared to ulcerative colitis (UC) and irritable bowel syndrome patients with respect to ASCA production as measured by ELISA. ASCA IgG or IgA positivity as well as change in titers over a period of up to 3 years (ΔIgG/A) was correlated with clinical parameters such as CD activity index (CDAI) and C-reactive protein levels (CRP). Moreover, two murine models of colitis (DSS and IL-10 knock out) were compared to control animals with respect to ASCA titers after oral yeast exposure.RESULTS: ASCA IgG and IgA titers are stable over time in CD and non-CD patients. Fistular disease was associated with a higher rate of ASCA IgA positivity (P = 0.014). Ileal disease was found to have a significant influence on the ΔIgG of ASCA (P=0.032). There was no correlation found between ASCA positivity or ΔIgG/A and clinical parameters of CD: CDAI and CRP. In mice,neither healthy animals nor animals with DSS-induced or spontaneous colitis exhibited a marked increase in ASCA titers after high-dose yeast exposure. On the other hand, mice immunized intraperitoneally with mannan plus adjuvant showed a marked and significant increase in ASCA titers compared to adjuvant-only immunized controls (P=0.014).CONCLUSION: The propensity to produce ASCA in a subgroup of CD patients is largely genetically predetermined as evidenced by their stability and lack of correlation with clinical disease activity parameters. Furthermore,in animal models of colitis, mere oral exposure of mice to yeast does not lead to the induction of marked ASCA titers irrespective of concomitant colonic inflammation.Hence, environment may play only a minor role in inducing ASCA.

  6. Dramatic Changes of Matrix Metalloproteinases-7 and Lysozyme in the Ulcerative Colitis of Mice Induced by Dextran Sulfate Sodium

    Institute of Scientific and Technical Information of China (English)

    KANG Jing-jing; YANG Yu-rong; LIANG Hong-de; ZHAO De-ming; TENG Ke-dao; JIAO Xi-lan; WANG Ping-li; SUN Zhe; NI Pei-pei; WANG Zhi-feng; ZHANG Rui

    2014-01-01

    Ulcerative colitis (UC) is a lifelong illness with profound emotional and social impacts, and could cause serious damage to large intestine, especially in colon. However, the pathogenesis of UC remained unclear. The present study attempts to ifnd out the role of matrix metalloproteinases-7 (MMP-7) and lysozyme in the pathogenesis of UC through a mice model induced by dextran sulfate sodium (DSS). The UC model was evaluated both by disease activity index (DAI) and the intestinal histopathology. The results show that there is a high correlation between the DAI score and the pathological changes of colon. Interleukin-6 (IL-6) serum levels and large intestinal lfuids levels in UC mice are always higher than that of the control groups, which might be associated with the degree of the inlfammation damage in the colon. The change tendency of the MMP-7 mRNA and protein expressions are both up-regulated ifrstly and then down-regulated from 1 to 5 d in the colon, but only the MMP-7 protein is up-regulated at 7 d again. The up-regulated MMP-7 levels in the early stage of UC may play a protective role through the activated defensins, while the down-regulated levels in the mid-later stage of UC may be connected with the severe lesions in the colon. However, the up-regulated MMP-7 levels in the later stage of UC in the colon may also contribute to the tissue repair or be served as a marker to CRC (colorectal cancer). The distribution of lysozyme protein indicates that there may be Paneth-like cells in the colon. Both the changes of MMP-7 and lysozyme in the small intestine may play a protective role for the safe environment of the whole gut, especially to the colon of UC.

  7. Effects of AP‑1 and NF‑κB inhibitors on colonic endocrine cells in rats with TNBS‑induced colitis.

    Science.gov (United States)

    El-Salhy, Magdy; Umezawa, Kazuo

    2016-08-01

    Interactions between intestinal neuroendocrine peptides/amines and the immune system appear to have an important role in the pathophysiology of inflammatory bowel disease (IBD). The present study investigated the effects of activator protein (AP)‑1 and nuclear factor (NF)‑κB inhibitors on inflammation‑induced alterations in enteroendocrine cells. A total of 48 male Wistar rats were divided into the following four groups (n=12 rats/group): Control, trinitrobenzene sulfonic acid (TNBS)‑induced colitis only (TNBS group), TNBS‑induced colitis with 3‑[(dodecylthiocarbonyl)-methyl]-glutarimide (DTCM‑G) treatment (DTCM‑G group), and TNBS‑induced colitis with dehydroxymethylepoxyquinomicin (DHMEQ) treatment (DHMEQ group). A total of 3 days following administration of TNBS, the rats were treated as follows: The control and TNBS groups received 0.5 ml vehicle (0.5% carboxymethyl cellulose; CMC), respectively; the DTCM‑G group received DTCM‑G (20 mg/kg body weight) in 0.5% CMC; and the DHMEQ group received DHMEQ (15 mg/kg body weight) in 0.5% CMC. All injections were performed intraperitoneally twice daily for 5 days. The rats were sacrificed, and tissue samples obtained from the colon were examined histopathologically and immunohistochemically. Inflammation was evaluated using a scoring system. In addition, the sections were immunostained for chromogranin A (CgA), serotonin, peptide YY (PYY), oxyntomodulin, pancreatic polypeptide (PP) and somatostatin, and immunostaining was quantified using image‑analysis software. The density of cells expressing CgA, PYY and PP was significantly lower in the TNBS group compared with in the control group, whereas the density of cells expressing serotonin, oxyntomodulin and somatostatin was significantly higher in the TNBS group compared with in the control group. None of the endocrine cell types differed significantly between the control group and either the DTCM‑G or DHMEQ groups. All of the colonic

  8. Intestinal microecology in rats with ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    韩晓霞

    2013-01-01

    Objective To study the abundance and diversity ofthe gut flora in rats with dextran sulfate sodium(DSS)-induced ulcerative colitis(UC)to provide new knowledge about the pathogenesis of this disease.Methods Twenty-six

  9. Treatment of experimental ulcerative colitis.

    Science.gov (United States)

    Lazebnik, L B; Lychkova, A E; Knyazev, O V

    2012-10-01

    The effects of infliximab, an anticytokine drug, on the course of inflammatory process was studied on the model of ulcerative colitis induced by injection of picrylsulfonic acid. Infliximab prevented the development of toxic dilatation and a drop of bioelectric activity of smooth muscles via maintenance of activity of the intramural nervous system neurons. PMID:23113311

  10. IL-18Rα-deficient CD4+T cells induce intestinal inflammation in the CD45RBhitransfer model of colitis despite impaired innate responsiveness

    DEFF Research Database (Denmark)

    Holmkvist, Petra; Pool, Lieneke; Hägerbrand, Karin;

    2016-01-01

    IL-18 has been implicated in inflammatory bowel disease (IBD), however its role in the regulation of intestinal CD4+ T-cell function remains unclear. Here we show that murine intestinal CD4+ T cells express high levels of IL-18Rα and provide evidence that IL-18Rα expression is induced on these ce......IL-18 has been implicated in inflammatory bowel disease (IBD), however its role in the regulation of intestinal CD4+ T-cell function remains unclear. Here we show that murine intestinal CD4+ T cells express high levels of IL-18Rα and provide evidence that IL-18Rα expression is induced...... on these cells subsequent to their entry into the intestinal mucosa. Using the CD45RBhi T-cell transfer colitis model, we show that IL-18Rα is expressed on IFN-γ+, IL-17+ and IL-17+IFN-γ+ effector CD4+ T cells in the inflamed colonic lamina propria (cLP) and mesenteric lymph node (MLN) and is required...... for the optimal generation and/or maintenance of IFN-γ-producing cells in the cLP. In the steady state and during colitis, TCR-independent cytokine-induced IFN-γ and IL-17 production by intestinal CD4+ T cells was largely IL-18Rα−dependent. Despite these findings however, IL-18Rα−deficient CD4+ T cells induced...

  11. The complement anaphylatoxin C3a receptor (C3aR contributes to the inflammatory response in dextran sulfate sodium (DSS-induced colitis in mice.

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    Elisabeth Wende

    Full Text Available Inflammatory bowel diseases are a critical public health issue, and as treatment options remain limited, there is a need to unravel the underlying pathomechanisms in order to identify new therapeutic targets. Complement activation was found in patients suffering from inflammatory bowel disease, and the complement anaphylatoxin C5a and its receptor C5aR have been implicated in disease pathogenesis in animal models of bowel inflammation. To further characterize complement-related pathomechanisms in inflammatory bowel disease, we have investigated the role of the anaphylatoxin C3a receptor in acute dextran sulfate sodium-induced colitis in mice. For this, colitis was induced in C3a receptor-deficient BALB/c and C57BL/6 mice, and disease severity was evaluated by clinical and histological examination, and by measuring the mRNA expression or protein levels of inflammatory mediators in the tissue. C3a receptor deficiency was partially protective in BALB/c mice, which had significantly reduced weight loss, clinical and histological scores, colon shortening, and CXCL-1/KC mRNA, myeloperoxidase and interleukin-6 tissue levels compared to the corresponding wild type mice. In C57BL/6 mice the differences between wild type and C3a receptor-deficient animals were much smaller and reached no significance. Our data demonstrate that the contribution of C3a receptor to disease pathogenesis and severity of dextran sulfate sodium-induced colitis in mice depends on the genetic background. Further studies will be required to clarify whether targeting of C3a receptor, possibly in combination with C5a receptor, might be considered as a therapeutic strategy for inflammatory bowel disease.

  12. Maternal exposure to low levels of corticosterone during lactation protects against experimental inflammatory colitis-induced damage in adult rat offspring.

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    Carla Petrella

    Full Text Available Opposing emotional events (negative/trauma or positive/maternal care during the postnatal period may differentially influence vulnerability to the effects of stress later in life. The development and course of intestinal disorders such as inflammatory bowel disease are negatively affected by persistent stress, but to date the role of positive life events on these pathologies has been entirely unknown. In the present study, the effect of early life beneficial experiences in the development of intestinal dysfunctions, where inflammation and stress stimuli play a primary role, was investigated. As a "positive" experimental model we used adult male rat progeny nursed by mothers whose drinking water was supplemented with moderate doses of corticosterone (CORT (0.2 mg/ml during the lactation period. Such animals have been generally shown to cope better with different environmental situations during life. The susceptibility to inflammatory experimental colitis induced by intracolonic infusion of TNBS (2,4,6-trinitrobenzenesulphonic acid was investigated in CORT-nursed rats in comparison with control rats. This mild increase in maternal corticosterone during lactation induced, in CORT-nursed rats, a long lasting protective effect on TNBS-colitis, characterized by improvements in some indices of the disease (increased colonic myeloperoxidase activity, loss of body weight and food intake and by the involvement of endogenous peripheral pathways known to participate in intestinal disorder development (lower plasma corticosterone levels and colonic mast cell degranulation, alterations in the colonic expression of both corticotrophin releasing factor/CRF and its receptor/CRH-1R. All these findings contribute to suggesting that the reduced vulnerability to TNBS-colitis in CORT-nursed rats is due to recovery from the colonic mucosal barrier dysfunction. Such long lasting changes induced by mild hormonal manipulation during lactation, making the adult also

  13. Influence of Shenqing Recipe on Morphology and Quantity of Colonic Interstitial Cells of Cajal in Trinitrobenzene Sulfonic Acid Induced Rat Colitis

    Institute of Scientific and Technical Information of China (English)

    Yan-cheng Dai; Zhi-peng Tang; Zhen-nan Wang; Ya-li Zhang; Xin-ying He

    2011-01-01

    Objective To observe the influence of Shenqing Recipe (SQR), a kind of Traditional Chinese Medicine, on the morphology and quantity of colonic interstitial cells of Cajal (ICC) in trinitrobenzene sulfonic acid (TNBS)-induced rat colitis, and to investigate the possible mechanism of SQR in regulating intestinal dynamics. Methods Sixty rats were randomly divided into normal control, model I , model Ⅱ, mesalazine,and high-dose, and low-dose SQR groups with 10 rats in each group. TNBS (10 mg) dissolved in 50% ethanol was instilled into the lumen of the rat colon of the latter five groups to induce colitis. On the 4th day after administration of TNBS, each treatment group was administered one of the following formulations by enteroclysis gavage once a day for 7 days: 600 mg·kg-1·d-1mesalazine, 2.4 g·kg-1·d-1 SQR, and 1.2 g·kg-1·d-1 SQR. Model Ⅱ rats received normal saline solution. After 7 days colonic samples were collected. While the colonic samples of model Ⅰ group were collected on the 3rd day after TNBS administered. Ultrastructure of ICC in the damaged colonic tissues was observed with transmission electron microscope. Expression of c-kit protein in colonic tissue was determined by immunohistochemical staining and Western blot. Results The ultrastructure of colonic ICC in the rat model of TNBS-induced colitis showed a severe injury, and administration of SQR or mesalazine reduced the severity of injury. Similarly, the expression of c-kit protein of TNBS-induced colitis rat model was significantly decreased compared with the normal control group (P<0.05). Treatment with SQR or mesalazine significantly increased the expression of c-kit protein compared with the administration of control formulations (P<0.05), especially the high-dose SQR group.Conclusion SQR could alleviate and repair the injured ICC, and improve its quantity, which might be involved in regulating intestinal motility.

  14. Anti-inflammatory effect of interleukin-10 in rabbit immune complex-induced colitis

    NARCIS (Netherlands)

    Grool, TA; Van Dullemen, H; Meenan, J; Koster, F; Ten Kate, FJW; Lebeaut, A; Tytgat, GNJ; Van Deventer, SJH

    1998-01-01

    Background: Interleukin-10 (IL-10) is an anti-inflammatory cytokine that downregulates the secretion of pro-inflammatory cytokines and additionally induces the secretion of anti-inflammatory cytokines, thus possibly leading to reduction of chronic inflammation in inflammatory bowel disease. In this

  15. Effects of trefoil peptide 3 on expression of TNF-alpha, TLR4, and NF-kappaB in trinitrobenzene sulphonic acid induced colitis mice.

    Science.gov (United States)

    Teng, Xu; Xu, Ling-Fen; Zhou, Ping; Sun, Hong-Wei; Sun, Mei

    2009-04-01

    The trefoil factor (TFF) peptides are major secretory products of mucus cells of the gastrointestinal tract. There were evidences that administration of recombinant human TFF3 is effective in treatment of models of colitis, but the mechanism of the effects of rTFF3 is not fully understood. The main aims of this study is to evaluate effects of intraperitoneal injection recombinant human TFF3 on the expression of tumour necrosis factor alpha (TNF-alpha), toll-like receptor 4(TLR4), and nuclear factor kappaB (NF-kappaB) in trinitrobenzene sulphonic acid (TNBS) induced colitis mice. Distal colitis was induced in BALB/C mice by intracolonic administration of TNBS in ethanol. Treated with administration rhTFF3 for treatment group(5 mg/ml; approximately 0.5 mg/mouse), and normal saline for control for 5 consecutive days. Colonic damage score, tissue myeloperoxidase (MPO) activity, TLR4, NF-kappaB mRNA expression, and tissue TNF-alpha, TLR4, NF-kappaB production were determined, respectively. Once daily application of hTFF3 for 5 days after TNBS/ethanol had been injected, both microscopic and macroscopic injury and inflammatory index had been reduced compared with controls. In addition, decreased tissue TNF-alpha, TLR4, NF-kappaB production, and TLR4, NF-kappaB mRNA expression had been found. This study has shown that hTFF3 may have therapeutic potential in the treatment of inflammatory bowel disease, and one of the mechanisms may related to inhibit the TLR4/NF-kappaB signaling pathways.

  16. Complications of collagenous colitis

    OpenAIRE

    Freeman, Hugh James

    2008-01-01

    Microscopic forms of colitis have been described, including collagenous colitis. This disorder generally has an apparently benign clinical course. However, a number of gastric and intestinal complications, possibly coincidental, may develop with collagenous colitis. Distinctive inflammatory disorders of the gastric mucosa have been described, including lymphocytic gastritis and collagenous gastritis. Celiac disease and collagenous sprue (or collagenous enteritis) may occur. Colonic ulceration...

  17. Infliximab induces clinical, endoscopic and histological responses in refractory ulcerative colitis Infliximab induce respuesta clínica, endoscópica e histológica en la colitis ulcerosa refractaria

    Directory of Open Access Journals (Sweden)

    F. Bermejo

    2004-02-01

    Full Text Available Background: infliximab is a monoclonal antiTNF-α antibody that has repeatedly shown to be effective in the management of Crohn's disease. However, data are scarce about its efficacy in ulcerative colitis. Aim: to describe the joint experience of three Spanish hospitals in the use of infliximab in patients with active refractory ulcerative colitis. Patients and methods: we present seven cases of ulcerative colitis (6 with chronic active disease despite immunosuppressive therapy, and one with acute steroid-refractory ulcerative colitis treated with infliximab 5 mg/kg of body weight. Clinical response was evaluated by means of the Clinical Activity Index at 2, 4 and 8 weeks after initial infusion. Biochemical (erythrocyte sedimentation rate and C-reactive protein, endoscopic, and histological changes were also assessed. Results: mean age of patients was 45.8 ± 17 years (range 23-77; 4 were female. No adverse effects were recorded. Inflammatory activity diminished significantly in 6 of 7 patients (85.7%; CI 95%: 42-99% both from a clinical (p = 0.01 and biochemical (p Introducción: infliximab, un anticuerpo monoclonal quimérico antiTNF-α ha demostrado su eficacia en pacientes con enfermedad de Crohn. Sin embargo, son escasos los datos sobre su efectividad en el tratamiento de la colitis ulcerosa. Objetivo: describir la experiencia conjunta de 3 hospitales españoles en el uso de infliximab en enfermos con CU activa resistente a otros tratamientos. Pacientes y métodos: se presentan 7 casos de colitis ulcerosa (6 con enfermedad crónicamente activa a pesar de tratamiento con inmunosupresor y 1 con colitis aguda grave refractaria a esteroides tratados con infliximab a dosis de 5 mg/kg de peso. Se evaluó la respuesta clínica mediante un Índice de Actividad Clínica trascurridas 2, 4 y 8 semanas de la infusión inicial. Así mismo, se estudiaron los cambios analíticos (velocidad de sedimentación y proteína C reactiva, endoscópicos e histol

  18. Expression and significance of nuclear factor κB p65 in colon tissues of rats with TNBS-induced colitis

    Institute of Scientific and Technical Information of China (English)

    Jun-Hua Li; Jie-Ping Yu; Hong-Gang Yu; Xi-Ming Xu; Liang-Liang Yu; Shi-Quan Liu

    2005-01-01

    AIM: To investigate the role of NF-κB in the pathogenesis of TNBS-induced colitis in rats.METHODS: Thirty-two healthy adult Sprague-Dawley (SD)rats were randomly divided into four groups of eight each:normal, NS, model I, model Ⅱ groups in our study. Rat colitis model was established through 2-,4-,6-trinitrobenzene sulfonic acid (TNBS) enema. At the end of four weeks,the macroscopical and histological changes of the colon were examined and mucosa myeloperoxidase (MPO)activities assayed. NF-κB p65 expression was determined by Western blot assessment in cytoplasmic and nuclear extracts of colon tissue, and the expressions of TNF-αand ICAM-1 protein in colon tissue were examined by immunohistochemistry. The relativities between expression of NF-κBp65 and other parameters were analyzed.RESULTS: TNBS enema resulted in pronounced pathological changes of colonic mucosa in model Ⅱ group (macroscopic and histological injury indices 6.25±1.39 and 6.24±1.04,respectively), which were in accordance with the significantly elevated MPO activity (1.69±0.11). And the nuclear level of NF-κB and expression of TNF-α, ICAM-1 in rats of model Ⅱ group were higher than that of normal control (9.7±1.96 vs1.7±0.15, 84.09±14.52 vs16.03±6.21,77.69±8.09 vs13.41±4.91 P<0.01), Linear correlation analysis revealed that there were strong correlations between the nuclear level of NF-κB and the tissue positive expression of TNF-α and ICAM-1, MPO activities,macroscopical and histological indices in TNBS-induced colitis, respectively (r = 0.8235, 0.8780, 0.8572, 0.9152,0.8247; P<0.05).CONCLUSION: NF-κB plays a pivotal role in the pathogenesis of ulcerative colitis, which might account for the up-regulation the expression of TNF-α and ICAM-1.

  19. Proanthocyanidins from Grape Seeds Modulate the NF-κB Signal Transduction Pathways in Rats with TNBS-Induced Ulcerative Colitis

    Directory of Open Access Journals (Sweden)

    Yongjie Wu

    2011-08-01

    Full Text Available To elucidate the molecular mechanisms involved in the therapeutic effects of proanthocyanidins from grape seeds (GSPE, we explore whether GSPE regulates the inflammatory response of TNBS-induced colitis in rats at the levels of NF-κB signal transduction pathway. Rats were intragastrically administered of different doses of GSPE (100, 200 and 400 mg·kg−1 per day for seven days after ulcerative colitis (UC was induced by intracolonic injection of 2,4,6-trinitrobenzenesulfonic acid (TNBS dissolved in 50% ethanol. Sulfasalazine (SASP at 400 mg/kg was used as a positive control drug. The expression of nuclear factor-kappa B (NF-κB, phospho-I kappaB-alpha (pIκBα, inhibitor kappa B kinase (IκK in the colon tissues were all measured by enzyme-linked immunosorbent assay (ELISA methods. Treatment with GSPE reduced the expression of NF-κB, pIκBα and IκK in the colon. The results of this study show that GSPE exerts beneficial effects in inflammatory bowel disease by inhibition of NF-κB signal transduction pathways.

  20. Andrographolide derivative AL-1 ameliorates TNBS-induced colitis in mice: involvement of NF-кB and PPAR-γ signaling pathways.

    Science.gov (United States)

    Yang, Yali; Yan, Hui; Jing, Mei; Zhang, Zaijun; Zhang, Gaoxiao; Sun, Yewei; Shan, Luchen; Yu, Pei; Wang, Yuqiang; Xu, Lipeng

    2016-01-01

    Andrographolide is a traditional herb medicine, widely used in Asia for conditions involving inflammation. The andrographlide-lipoic acid conjugate, AL-1, has been found being able to alleviate inflammation in our previous reports. Although the anti-inflammatory activity of AL-1 contributes to its cytoprotective effects, whether AL-1 can improve inflammatory bowel disease (IBD) and the underlying mechanisms of its action remain largely unknown. In this study, we investigated the anti-inflammatory effects of AL-1 in C57BL/6 mice with trinitrobenzenesulfonic acid (TNBS)-induced colitis. The body weight loss and length change of colon after TNBS instillation were more severe than those in normal mice. AL-1 treatment led to significant reductions in disease activity index (DAI), macroscopic score and colon mucosa damage index (CMDI) associated with TNBS administration. AL-1 inhibited the inflammatory response via lowering the level of inflammatory cytokines and myeloperoxidase (MPO) activity. AL-1 attenuated the expression of p-p65, p-IκBα and COX-2 in the colitis mice. The alleviation of colon injury by AL-1 treatment was also evidenced by the increased expression of PPAR-γ. These results indicated that AL-1 could protect intestinal tract from the injury induced by TNBS in mice, suggesting that AL-1 may have potential in treatment for IBD.

  1. Anti-Inflammatory Effect of Recreational Exercise in TNBS-Induced Colitis in Rats: Role of NOS/HO/MPO System

    Directory of Open Access Journals (Sweden)

    Zita Szalai

    2014-01-01

    Full Text Available There are opposite views in the available literature: Whether physical exercise has a protective effect or not on the onset of inflammatory bowel disease (IBD. Therefore, we investigated the effects of recreational physical exercise before the induction of colitis. After 6 weeks of voluntary physical activity (running wheel, male Wistar rats were treated with TNBS (10 mg. 72 hrs after trinitrobenzene sulphonic acid (TNBS challenge we measured colonic gene (TNF-α, IL-1β, CXCL1 and IL-10 and protein (TNF-α expressions of various inflammatory mediators and enzyme activities of heme oxygenase (HO, nitric oxide synthase (NOS, and myeloperoxidase (MPO enzymes. Wheel running significantly increased the activities of HO, constitutive NOS (cNOS isoform. Furthermore, 6 weeks of running significantly decreased TNBS-induced inflammatory markers, including extent of lesions, severity of mucosal damage, and gene expression of IL-1β, CXCL1, and MPO activity, while IL-10 gene expression and cNOS activity were increased. iNOS activity decreased and the activity of HO enzyme increased, but not significantly, compared to the sedentary TNBS-treated group. In conclusion, recreational physical exercise can play an anti-inflammatory role by downregulating the gene expression of proinflammatory mediators, inducing anti-inflammatory mediators, and modulating the activities of HO and NOS enzymes in a rat model of colitis.

  2. Andrographolide derivative AL-1 ameliorates TNBS-induced colitis in mice: involvement of NF-кB and PPAR-γ signaling pathways.

    Science.gov (United States)

    Yang, Yali; Yan, Hui; Jing, Mei; Zhang, Zaijun; Zhang, Gaoxiao; Sun, Yewei; Shan, Luchen; Yu, Pei; Wang, Yuqiang; Xu, Lipeng

    2016-01-01

    Andrographolide is a traditional herb medicine, widely used in Asia for conditions involving inflammation. The andrographlide-lipoic acid conjugate, AL-1, has been found being able to alleviate inflammation in our previous reports. Although the anti-inflammatory activity of AL-1 contributes to its cytoprotective effects, whether AL-1 can improve inflammatory bowel disease (IBD) and the underlying mechanisms of its action remain largely unknown. In this study, we investigated the anti-inflammatory effects of AL-1 in C57BL/6 mice with trinitrobenzenesulfonic acid (TNBS)-induced colitis. The body weight loss and length change of colon after TNBS instillation were more severe than those in normal mice. AL-1 treatment led to significant reductions in disease activity index (DAI), macroscopic score and colon mucosa damage index (CMDI) associated with TNBS administration. AL-1 inhibited the inflammatory response via lowering the level of inflammatory cytokines and myeloperoxidase (MPO) activity. AL-1 attenuated the expression of p-p65, p-IκBα and COX-2 in the colitis mice. The alleviation of colon injury by AL-1 treatment was also evidenced by the increased expression of PPAR-γ. These results indicated that AL-1 could protect intestinal tract from the injury induced by TNBS in mice, suggesting that AL-1 may have potential in treatment for IBD. PMID:27435110

  3. Laser Induced Surface Chemical Epitaxy

    Science.gov (United States)

    Stinespring, Charter D.; Freedman, Andrew

    1990-02-01

    Studies of the thermal and photon-induced surface chemistry of dimethyl cadmium (DMCd) and dimethyl tellurium (DMTe) on GaAs(100) substrates under ultrahigh vacuum conditions have been performed for substrate temperatures in the range of 123 K to 473 K. Results indicate that extremely efficient conversion of admixtures of DMTe and DMCd to CdTe can be obtained using low power (5 - 10 mJ cm-2) 193 nm laser pulses at substrate temperatures of 123 K. Subsequent annealing at 473 K produces an epitaxial film.

  4. Neuroprotective Potential of Mesenchymal Stem Cell-Based Therapy in Acute Stages of TNBS-Induced Colitis in Guinea-Pigs.

    Directory of Open Access Journals (Sweden)

    Ainsley M Robinson

    Full Text Available The therapeutic benefits of mesenchymal stem cells (MSCs, such as homing ability, multipotent differentiation capacity and secretion of soluble bioactive factors which exert neuroprotective, anti-inflammatory and immunomodulatory properties, have been attributed to attenuation of autoimmune, inflammatory and neurodegenerative disorders. In this study, we aimed to determine the earliest time point at which locally administered MSC-based therapies avert enteric neuronal loss and damage associated with intestinal inflammation in the guinea-pig model of colitis.At 3 hours after induction of colitis by 2,4,6-trinitrobenzene-sulfonate (TNBS, guinea-pigs received either human bone marrow-derived MSCs, conditioned medium (CM, or unconditioned medium by enema into the colon. Colon tissues were collected 6, 24 and 72 hours after administration of TNBS. Effects on body weight, gross morphological damage, immune cell infiltration and myenteric neurons were evaluated. RT-PCR, flow cytometry and antibody array kit were used to identify neurotrophic and neuroprotective factors released by MSCs.MSC and CM treatments prevented body weight loss, reduced infiltration of leukocytes into the colon wall and the myenteric plexus, facilitated repair of damaged tissue and nerve fibers, averted myenteric neuronal loss, as well as changes in neuronal subpopulations. The neuroprotective effects of MSC and CM treatments were observed as early as 24 hours after induction of inflammation even though the inflammatory reaction at the level of the myenteric ganglia had not completely subsided. Substantial number of neurotrophic and neuroprotective factors released by MSCs was identified in their secretome.MSC-based therapies applied at the acute stages of TNBS-induced colitis start exerting their neuroprotective effects towards enteric neurons by 24 hours post treatment. The neuroprotective efficacy of MSC-based therapies can be exerted independently to their anti

  5. A Systems Biology-Based Approach to Uncovering the Molecular Mechanisms Underlying the Effects of Dragon's Blood Tablet in Colitis, Involving the Integration of Chemical Analysis, ADME Prediction, and Network Pharmacology

    OpenAIRE

    Haiyu Xu; Yanqiong Zhang; Yun Lei; Xiumei Gao; Huaqiang Zhai; Na Lin; Shihuan Tang; Rixin Liang; Yan Ma; Defeng Li; Yi Zhang; Guangrong Zhu; Hongjun Yang; Luqi Huang

    2014-01-01

    Traditional Chinese medicine (TCM) is one of the oldest East Asian medical systems. The present study adopted a systems biology-based approach to provide new insights relating to the active constituents and molecular mechanisms underlying the effects of dragon's blood (DB) tablets for the treatment of colitis. This study integrated chemical analysis, prediction of absorption, distribution, metabolism, and excretion (ADME), and network pharmacology. Firstly, a rapid, reliable, and accurate ult...

  6. NCB-02(standardized Curcumin preparation)protects dinitrochlorobenzene-induced colitis through down-regulation of NFκ-B and iNOS

    Institute of Scientific and Technical Information of China (English)

    MV Venkataranganna; Md Rafiq; S Gopumadhavan; Ghouse Peer; UV Babu; SK Mitra

    2007-01-01

    AIM:To evaluate the efficacy and mechanism of action of NCB-02,a standardized Curcumin preparation,against 2,4-dinitrochlorobenzene(DNCB)-induced ulcerative colitis in rats.METHODS:Ulcerative colitis was induced in male rats by sensitizing with topical application of DNCB in acetone for 14 d and intra-colonol challenge with DNCB on day 15.A separate group of animals with vehicle treatment in similar fashion served as control group.Colitis rats were divided into different groups and treated with NCB-02 at doses of 25,50 and 100 mg/kg b.wt p.o.for 10 d.Sulfasalazine at a dose of 100 mg/kg b.wt for 10 d served as a reference group.On day 10 after respective assigned treatment,all the animals were euthanized and the length of the colon,weight of entire colon and distal 8 cm of the colon were recorded.The distal part of the colon was immediately observed under a stereomicroscope and the degree of damage was scored.Further distal 8 cm of the colon was subject to the determination of colonic myeloperoxidase(MPO),lipid peroxidation(LPO)and alkaline phosphatase (ALP)activities.A small piece of the sample from distal colon of each animal was fixed in 10% neutral buffered formalin and embedded in paraffin wax and sectioned for immunohistochemical examination of NFκ-B and iNOS expression.RESULTS:NCB-02 showed a dose dependent protection against DNCB-induced alteration in colon length and weight.NCB-02 treatment also showed a dose dependent protection against the elevated levels of MPO,LPO and ALP,induced by DNCB.NCB-02 demonstrated a significant effect at a dose of 100 mg/kg b.wt.,which was almost equipotent to 100 mg/kg b.wt.of sulfasalazine.Treatment with sulfasalazine and curcumin at a dose of 100 mg/kg b.wt.inhibited the DNCB-induced overexpression of NFκ-B and iNOS in the colon.CONCLUSION:Curcumin treatment ameliorates colonic damage in DNCB-induced colitic rats,an effect associated with an improvement in intestinal oxidative stress and downregulation of colonic NFκ

  7. Inherited CARD9 deficiency in otherwise healthy children and adults with Candida species-induced meningoencephalitis, colitis, or both.

    OpenAIRE

    Lanternier, Fanny; Mahdaviani, Seyed Alireza; Barbati, Elisa; Chaussade, Hélène; Koumar, Yatrika; Levy, Romain; Denis, Blandine; Brunel, Anne-Sophie; Martin, Sophie; Loop, Michèle; Peeters, Julie; de Selys, Ariel; Vanclaire, Jean; Vermylen, Christiane; Nassogne, Marie-Cécile

    2015-01-01

    Invasive infections of the central nervous system or digestive tract caused by commensal fungi of the genus Candida are rare and life-threatening. The known risk factors include acquired and inherited immunodeficiencies, with patients often displaying a history of multiple infections. Cases of meningo-encephalitis and/or colitis caused by Candida remain unexplained. We studied five previously healthy children and adults with unexplained invasive disease of the central nervous system, or the d...

  8. Na-H Exchanger Isoform-2 (NHE2) Mediates Butyrate-dependent Na+ Absorption in Dextran Sulfate Sodium (DSS)-induced Colitis.

    Science.gov (United States)

    Rajendran, Vazhaikkurichi M; Nanda Kumar, Navalpur S; Tse, Chung M; Binder, Henry J

    2015-10-16

    Diarrhea associated with ulcerative colitis (UC) occurs primarily as a result of reduced Na(+) absorption. Although colonic Na(+) absorption is mediated by both epithelial Na(+) channels (ENaC) and Na-H exchangers (NHE), inhibition of NHE-mediated Na(+) absorption is the primary cause of diarrhea in UC. As there are conflicting observations reported on NHE expression in human UC, the present study was initiated to identify whether NHE isoforms (NHE2 and NHE3) expression is altered and how Na(+) absorption is regulated in DSS-induced inflammation in rat colon, a model that has been used to study UC. Western blot analyses indicate that neither NHE2 nor NHE3 expression is altered in apical membranes of inflamed colon. Na(+) fluxes measured in vitro under voltage clamp conditions in controls demonstrate that both HCO3 (-)-dependent and butyrate-dependent Na(+) absorption are inhibited by S3226 (NHE3-inhibitor), but not by HOE694 (NHE2-inhibitor) in normal animals. In contrast, in DSS-induced inflammation, butyrate-, but not HCO3 (-)-dependent Na(+) absorption is present and is inhibited by HOE694, but not by S3226. These observations indicate that in normal colon NHE3 mediates both HCO3 (-)-dependent and butyrate-dependent Na(+) absorption, whereas DSS-induced inflammation activates NHE2, which mediates butyrate-dependent (but not HCO3 (-)-dependent) Na(+) absorption. In in vivo loop studies HCO3 (-)-Ringer and butyrate-Ringer exhibit similar rates of water absorption in normal rats, whereas in DSS-induced inflammation luminal butyrate-Ringer reversed water secretion observed with HCO3 (-)-Ringer to fluid absorption. Lumen butyrate-Ringer incubation activated NHE3-mediated Na(+) absorption in DSS-induced colitis. These observations suggest that the butyrate activation of NHE2 would be a potential target to control UC-associated diarrhea.

  9. Protective effect of Clostridium tyrobutyricum in acute dextran sodium sulphate-induced colitis: differential regulation of tumour necrosis factor-a and interleukin-18 in BALB/c and severe combined immunodeficiency mice

    NARCIS (Netherlands)

    Hudcovic, T.; Kolinska, J.; Klepetar, J.; Stepankova, R.; Rezanka, T.; Srutkova, D.; Schwarzer, M.; Erban, V.; Du, Z.; Wells, J.; Hrncir, T.; Tlaskalova-Hogenova, H.; Kozakova, H.

    2012-01-01

    One of the promising approaches in the therapy of ulcerative colitis is administration of butyrate, an energy source for colonocytes, into the lumen of the colon. This study investigates the effect of butyrate producing bacterium Clostridium tyrobutyricum on dextran sodium sulphate (DSS)-induced col

  10. Role of nitric oxide in the impairment of circular muscle contractility of distended, uninflamed mid-colon in TNBS-induced acute distal colitis in rats

    Institute of Scientific and Technical Information of China (English)

    Luciano Onori; Giovanni Latella; Annalisa Aggio; Simona D'Alo'; Paola Muzi; Maria Grazia Cifone; Gabriella Mellillo; Rachele Ciccocioppo; Gennaro Taddei; Giuseppe Frieri

    2005-01-01

    AIM: To evaluate the role of nitric oxide (NO) in the motor disorders of the dilated uninflamed mid-colon (DUMC)from trinitrobenzene sulfonic acid (TNBS)-induced acute distal colitis in rats.METHODS: Colitis was induced in male Sprague-Dawley rats by a single intracolonic administration of TNBS.Control rats received an enema of 0.9% saline. The rats were killed 48 h after TNBS or saline administration.Macroscopic and histologic lesions of the colon were evaluated. Myeloperoxidase (MPO) and nitric oxide synthase (NOS) activity were measured on the colonic tissue. In TNBS rats, we evaluated spontaneous and evoked contractile activity in circular muscle strips derived from DUMC in comparison to the same colonic segment of control rats, both in the presence and in the absence of a non-selective NOS isoforms inhibitor N-nitro-Larginine (L-NNA). Pharmacological characterization of electric field stimulation (EFS)-evoked contractile responses was also performed.RESULTS: In TNBS rats, the distal colon showed severe histological lesions and a high MPO activity, while the DUMC exhibited normal histology and MPO activity.Constitutive NOS activity was similar in TNBS and control rats, whereas inducible NOS activity was significantly increased only in the injured distal colon of TNBS rats.Isometrically recorded mechanical activity of circular muscle strips from DUMC of TNBS rats showed a marked reduction of the force and frequency of spontaneous contractions compared to controls, as well as of the contractile responses to a contracting stimulus. In the presence of L-NNA, the contractile activity and responses displayed a significantly greater enhancement compared to controls. The pharmacological characterization of EFS contractile responses showed that a cooperative-like interaction between cholinergic muscarinic and tachykinergic neurokinin 1 and 2 receptors mediated transmission in DUMC of TNBS rats vs a simple additive interaction in controls.CONCLUSION: The results of this

  11. Pseudomembranous Colitis: Not Always Caused by Clostridium difficile

    Directory of Open Access Journals (Sweden)

    Derek M. Tang

    2014-01-01

    Full Text Available Although classically pseudomembranous colitis is caused by Clostridium difficile, it can result from several etiologies. Certain medications, chemical injury, collagenous colitis, inflammatory bowel disease, ischemia, and other infectious pathogens can reportedly cause mucosal injury and subsequent pseudomembrane formation. We present the case of a middle-aged woman with vascular disease who was incorrectly diagnosed with refractory C. difficile infection due to the presence of pseudomembranes. Further imaging, endoscopy, and careful histopathology review revealed chronic ischemia as the cause of her pseudomembranous colitis and diarrhea. This case highlights the need for gastroenterologists to consider non-C. difficile etiologies when diagnosing pseudomembranous colitis.

  12. Crohn's & Colitis Foundation of America

    Science.gov (United States)

    ... enabled to enjoy the full interactive experience. Crohn's & Colitis Foundation of America Find a Doctor Find a ... Local Chapters News Events Search: What are Crohn's & Colitis? What is Crohn's Disease What is Ulcerative Colitis ...

  13. A novel mouse model for colitis-associated colon carcinogenesis induced by 1,2-dimethylhydrazine and dextran sulfate sodium

    Institute of Scientific and Technical Information of China (English)

    Jian-Guo Wang; Dong-Fei Wang; Bing-Jian Lv; Jian-Min Si

    2004-01-01

    AIM: To develop an efficient animal colitis-associated carcinogenesis model and to detect the expression of β-catenin and p53 in this new model.METHODS: Dysplasia and cancer were investigated in mice pretreated with a single intraperitoneal injection of 20 mg/kg body mass of 1,2-dimethylhydrazine prior to three repetitive oral administrations of 30 g/L dextran sulfate sodium to give conditions similar to the clinically observed active and remission phases. Immunohistochemical staining of β-catenin and p53 was performed on paraffin-imbedded specimens of animals with cancer and/or dysplasia, those without dysplasia and the normal control animals.RESULTS: At wk 11, four early-invasive adenocarcinomas and 36 dysplasia were found in 10 (90.9%) of the 11 mice that underwent 1,2-dimethylhydrazine-pretreatment with 3 cycles of 30 g/L dextran sulfate sodium-exposure. Dysplasia and/or cancer occurred as flat lesions or as dysplasia-associated lesion or mass (DALM) as observed in humans. Colorectal carcinogenesis occurred primarily on the distal portion of the large intestine. No dysplasia and/or cancer lesion was observed in the control groups with 1,2-dimethylhydrazine pretreatment or 3 cycles of 30 g/L dextran sulfate sodium exposure alone. Immunohistochemical investigation revealed that β-catenin was translocated from cell membrane to cytoplasm and/or nucleus in 100% of cases with dysplasia and neoplasm, while normal membrane staining was observed in cases without dysplasia and the normal control animals. Nuclear expression of p53 was not detected in specimens.CONCLUSION: A single dose of procarcinogen followed by induction of chronic ulcerative colitis results in a high incidence of colorectal dysplasia and cancer. Abnormal expression of β-catenin occurs frequently in dysplasia and cancer. This novel mouse model may provide an excellent vehicle for studying colitis-related colon carcinogenesis.

  14. Interleukin-6 Induces S100A9 Expression in Colonic Epithelial Cells through STAT3 Activation in Experimental Ulcerative Colitis

    OpenAIRE

    Lee, Min Jeoung; Lee, Jin-Ku; Choi, Ji Won; Lee, Chang-Seok; Sim, Ji Hyun; Cho, Chung-Hyun; Lee, Kwang-Ho; Cho, Ik-Hyun; Chung, Myung-Hee; Kim, Hang-Rae; Ye, Sang-Kyu

    2012-01-01

    Background Intestinal epithelium is essential for maintaining normal intestinal homeostasis; its breakdown leads to chronic inflammatory pathologies, such as inflammatory bowel diseases (IBDs). Although high concentrations of S100A9 protein and interleukin-6 (IL-6) are found in patients with IBD, the expression mechanism of S100A9 in colonic epithelial cells (CECs) remains elusive. We investigated the role of IL-6 in S100A9 expression in CECs using a colitis model. Methods IL-6 and S100A9 exp...

  15. Chemical bond cleavage induced by electron heating

    International Nuclear Information System (INIS)

    Gas emissions from titanium-metalloid compounds (titanium nitride and oxide) have been investigated to understand the effects of a microwave field on chemical reactions. We employed a high vacuum system (PO2 = 10−6 Pa) to observe in situ reductions. For titanium oxides, H-field heating significantly differed from conventional one in terms of oxygen emissions. For titanium nitride, the emissions were also induced by microwave heating. These tendencies were observed at temperatures above 1000 °C. A quantum chemical interpretation is provided to explain the emissions of the gases, and the experimental data is in good agreement with results predicted using the electronic energy band structure.

  16. Study of chemical and radiation induced carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Chmura, A.

    1995-11-01

    The study of chemical and radiation induced carcinogenesis has up to now based many of its results on the detection of genetic aberrations using the fluorescent in situ hybridization (FISH) technique. FISH is time consuming and this tends to hinder its use for looking at large numbers of samples. We are currently developing new technological advances which will increase the speed, clarity and functionality of the FISH technique. These advances include multi-labeled probes, amplification techniques, and separation techniques.

  17. Current treatment of ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    JohannesMeier; AndreasSturm

    2011-01-01

    Ulcerative colitis (UC) is a chronic disease featuring re- current inflammation of the colonic mucosa. The goal of medical treatment is to rapidly induce a steroid-free remission while at the same time preventing complica- tions of the disease itself and its treatment. The choice of treatment depends on severity, localization and the course of the disease. For proctitis, topical therapy with 5-aminosalicylic acid (5-ASA) compounds is used. More extensive or severe disease should be treated with oral and local 5-ASA compounds and corticosteroids to induce remission. Patients who do not respond to this treatment require hospitalization. Intravenous steroids or, when refractory, calcineurin inhibitors (cyclosporine, tacrolimus), tumor necrosis factor-α antibodies (infliximab) or immunomodulators (azathioprine, 6-mercaptopurine) are then called for. Indications for emergency surgery include refractory toxic megacolon, perforation, and continuous severe colorectal bleeding. Close collaboration between gastroenterologist and surgeon is mandatory in order not to delay surgical therapy when needed. This article is intended to give a general, practice-orientated overview of the key issues in ulcerative colitis treatment. Recommendations are based on published consensus guidelines derived from national and international guidelines on the treatment of ulcerative colitis.

  18. Current treatment of ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Johannes Meier; Andreas Sturm

    2011-01-01

    Ulcerative colitis (UC) is a chronic disease featuring recurrent inflammation of the colonic mucosa. The goal of medical treatment is to rapidly induce a steroid-free remission while at the same time preventing complications of the disease itself and its treatment. The choice of treatment depends on severity, localization and the course of the disease. For proctitis, topical therapy with 5-aminosalicylic acid (5-ASA) compounds is used. More extensive or severe disease should be treated with oral and local 5-ASA compounds and corticosteroids to induce remission. Patients who do not respond to this treatment require hospitalization. Intravenous steroids or, when refractory, calcineurin inhibitors (cyclosporine, tacrolimus), tumor necrosis factor-α antibodies (infliximab) or immunomodulators (azathioprine, 6-mercaptopurine) are then called for. Indications for emergency surgery include refractory toxic megacolon, perforation, and continuous severe colorectal bleeding. Close collaboration between gastroenterologist and surgeon is mandatory in order not to delay surgical therapy when needed. This article is intended to give a general, practice- orientated overview of the key issues in ulcerative colitis treatment. Recommendations are based on published consensus guidelines derived from national and international guidelines on the treatment of ulcerative colitis.

  19. Ethanol Extract of Cordyceps militaris Grown on Germinated Soybeans Attenuates Dextran-Sodium-Sulfate- (DSS- Induced Colitis by Suppressing the Expression of Matrix Metalloproteinases and Inflammatory Mediators

    Directory of Open Access Journals (Sweden)

    Dong Ki Park

    2013-01-01

    Full Text Available The effect of Cordyceps militaris (CM grown on germinated soybeans (GSC in the inflammatory bowel disease (IBD model was studied. To demonstrate the preventive effect of GSC extract in a dextran-sodium-sulfate- (DSS- induced acute colitis mouse model, GSC was administered 2 days before DSS coadministration. GSC significantly suppressed DSS-induced disease activity index (DAI as well as histopathological scores, compared to control or CM-treated group. To elucidate the anti-IBD activity of GSC, we checked the level of matrix metalloproteinases (MMPs and inflammatory mediators. GSC extract decreased the level of MMP-3 and -9 mRNAs and p53 proteins. The level and activity of LPS-induced MMP-9 were reduced in GSC-treated RAW264.7 cells. It also attenuated the level of inducible nitric oxide synthase (iNOS and tumor necrosis factor- (TNF- α mRNAs both in colon tissue and in macrophage cells. These results suggest that GSC can be applied as a protective agent against IBDs.

  20. Complications of collagenous colitis.

    Science.gov (United States)

    Freeman, Hugh-James

    2008-03-21

    Microscopic forms of colitis have been described, including collagenous colitis. This disorder generally has an apparently benign clinical course. However, a number of gastric and intestinal complications, possibly coincidental, may develop with collagenous colitis. Distinctive inflammatory disorders of the gastric mucosa have been described, including lymphocytic gastritis and collagenous gastritis. Celiac disease and collagenous sprue (or collagenous enteritis) may occur. Colonic ulceration has been associated with use of nonsteroidal anti-inflammatory drugs, while other forms of inflammatory bowel disease, including ulcerative colitis and Crohn's disease, may evolve from collagenous colitis. Submucosal "dissection", colonic fractures or mucosal tears and perforation from air insufflation during colonoscopy may occur and has been hypothesized to be due to compromise of the colonic wall from submucosal collagen deposition. Similar changes may result from increased intraluminal pressure during barium enema contrast studies. Finally, malignant disorders have also been reported, including carcinoma and lymphoproliferative disease. PMID:18350593

  1. Complications of collagenous colitis

    Institute of Scientific and Technical Information of China (English)

    Hugh James Freeman

    2008-01-01

    Microscopic forms of colitis have been described, including collagenous colitis. This disorder generally has an apparently benign clinical course. However, a number of gastric and intestinal complications, possibly coincidental, may develop with collagenous colitis. Distinctive inflammatory disorders of the gastric mucosa have been described, including lymphocytic gastritis and collagenous gastritis. Celiac disease and collagenous sprue (or collagenous enteritis) may occur. Colonic ulceration has been associated with use of nonsteroidal anti-inflammatory drugs, while other forms of inflammatory bowel disease, including ulcerative colitis and Crohn's disease, may evolve from collagenous colitis. Submucosal "dissection", colonic fractures or mucosal tears and perforation from air insufflation during colonoscopy may occur and has been hypothesized to be due to compromise of the colonic wall from submucosal collagen deposition. Similar changes may result from increased intraluminal pressure during barium enema contrast studies. Finally, malignant disorders have also been reported, including carcinoma and lymphoproliferative disease.

  2. GL-V9, a new synthetic flavonoid derivative, ameliorates DSS-induced colitis against oxidative stress by up-regulating Trx-1 expression via activation of AMPK/FOXO3a pathway.

    Science.gov (United States)

    Zhao, Yue; Sun, Yang; Ding, Youxiang; Wang, Xiaoping; Zhou, Yuxin; Li, Wenjun; Huang, Shaoliang; Li, Zhiyu; Kong, Lingyi; Guo, Qinglong; Lu, Na

    2015-09-22

    GL-V9, a new synthesized flavonoid derivative, has been reported to possess anti-cancer properties in our previous studies. Uncontrolled overproduction of reactive oxygen species (ROS) has been implicated in oxidative damage of inflammatory bowel disease (IBD). In this study, we aimed to investigate the protective effect of GL-V9 against dextran sulfate sodium (DSS)-induced colitis. GL-V9 attenuated DSS-induced body weight loss, colon length shortening and colonic pathological damage. GL-V9 also inhibited inflammatory cells infiltration and decreased myeloperoxidase (MPO) and inducible nitric oxide synthase (iNOS) activities. Moreover, GL-V9 inhibited ROS and malondialdehyde (MDA) generation, but enhanced superoxide dismutase (SOD), glutathione (GSH) and total antioxidant capacity. GL-V9 reduced pro-inflammatory cytokines production in serum and colon as well. Mechanically, GL-V9 could increase Trx-1 via activation of AMPK/FOXO3a to suppress DSS-induced colonic oxidative stress. Furthermore, GL-V9 decreased pro-inflammatory cytokines and ROS production and increased the antioxidant defenses in the mouse macrophage cells RAW264.7 by promoting Trx-1 expression. In conclusion, our study demonstrated that GL-V9 attenuated DSS-induced colitis against oxidative stress by up-regulating Trx-1 via activation of AMPK/FOXO3a pathway, suggesting that GL-V9 might be a potential effective drug for colitis.

  3. Monotropein isolated from the roots of Morinda officinalis ameliorates proinflammatory mediators in RAW 264.7 macrophages and dextran sulfate sodium (DSS)-induced colitis via NF-κB inactivation.

    Science.gov (United States)

    Shin, Ji-Sun; Yun, Kyung-Jin; Chung, Kyung-Sook; Seo, Kyeong-Hwa; Park, Hee-Juhn; Cho, Young-Wuk; Baek, Nam-In; Jang, Daesik; Lee, Kyung-Tae

    2013-03-01

    We previously demonstrated that monotropein isolated from the roots of Morinda officinalis (Rubiaceae) has anti-inflammatory effects in vivo. In the present study, we investigated the molecular mechanisms underlying the anti-inflammatory effects of monotropein in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages and dextran sulfate sodium (DSS)-induced colitis mouse model. Monotropein was found to inhibit the expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) mRNA in LPS-induced RAW 264.7 macrophages. Treatment with monotropein decreased the DNA binding activity of nuclear factor-κB (NF-κB). Consistent with these findings, monotropein also suppressed phosphorylation and degradation of inhibitory κB-α (IκB-α), and consequently the translocations of NF-κB. In the DSS-induced colitis model, monotropein reduced disease activity index (DAI), myeloperoxidase (MPO) activity, and inflammation-related protein expressions by suppressing NF-κB activation in colon mucosa. Taken together, these findings suggest that the anti-inflammatory effects of monotropein are mainly related to the inhibition of the expressions of inflammatory mediators via NF-κB inactivation, and support its possible therapeutic role in colitis. PMID:23261679

  4. Nitric oxide and chronic colitis

    Directory of Open Access Journals (Sweden)

    Matthew B Grisham

    1996-01-01

    Full Text Available Nitric oxide (NO is thought to play an important role in modulating the inflammatory response by virtue of its ability to affect bloodflow, leukocyte function and cell viability. The objective of this study was to assess the role that NO may play in mediating the mucosal injury and inflammation in a model of chronic granulomatous colitis using two pharmacologically different inhibitors of nitric oxide synthase (NOS. Chronic granulomatous colitis with liver and spleen inflammation was induced in female Lewis rats via the subserosal (intramural injection of peptidoglycan/polysaccharide (PG/PS derived from group A streptococci. Chronic NOS inhibition by oral administration of NG-nitro-L-arginine methyl ester (L-NAME (15 µmol/kg/day or amino-guanidine (AG (15 µmol/ kg/day was found to attenuate the PG/PS-induced increases in macroscopic colonic inflammation scores and colonic myeloperoxidase activity. Only AG -- not L-NAME – attenuated the PG/PS-induced increases in colon dry weight. Both L-NAME and AG significantly attenuated the PG/PS-induced increases in spleen weight whereas neither was effective at significantly attenuating the PG/PS-induced increases in liver weight. Although both L-NAME and AG inhibited NO production in vivo, as measured by decreases in plasma nitrite and nitrate levels, only AG produced significantly lower values (38±3 versus 83±8 µM, respectively, P<0.05. Finally, L-NAME, but not AG, administration significantly increased mean arterial pressure from 83 mmHg in colitic animals to 105 mmHg in the PG/PS+ L-NAME-treated animals (P<0.05. It is concluded that NO may play an important role in mediating some of the pathophysiology associated with this model of chronic granulomatous colitis.

  5. Favorable response to subcutaneous administration of infliximab in rats with experimental colitis

    Institute of Scientific and Technical Information of China (English)

    John K Triantafillidis; Helen Sotiriou; Apostolos E Papalois; Aikaterini Parasi; Emmanuel Anagnostakis; Stavros Burnazos; Aristofanis Gikas; Emmanuel G Merikas; Emmanuel Douzinas; Maria Karagianni

    2005-01-01

    AIM: To investigate the influence of infliximab (Remicade)on experimental colitis produced by 2,4,6,trinitrobenzene sulfonic acid (TNBS) in rats.METHODS: Thirty-six Wistar rats were allocated into four groups (three groups of six animals each and a fourth of 12 animals). Six more healthy animals served as normal controls (Group 5). Group 1:colitis was induced by intracolonic installation of 25 mg of TNBS dissolved in 0.25 mL of 50% ethanol and infliximab was subcutaneously administered at a dose of 5 mg/kg BW; Group 2: colitis was induced and infliximab was subcutaneously administered at a dose of 10 mg/kg BW; Group 3: colitis was induced and infliximab was subcutaneously administered at a dose of 15 mg/kg BW; Group 4: colitis was induced without treatment with infliximab. Infliximab was administered on d 2-6. On the 7th d, all animals were killed. The colon was fixed in 10%buffered formalin and examined by light microscopy for the presence and activity of colitis and the extent of tissue damage. Tumor necrosis factor-alpha (TNF-α) and malondialdehyde (MDA) were also measured.RESULTS: Significant differences concerning the presence of reparable lesions and the extent of bowel mucosa without active inflammation in all groups of animals treated with infliximab compared with controls were found. Significant reduction of the tissue levels of TNF-α in all groups of treated animals as compared withthe untreated ones was found (0.47±0.44, 1.09±0.86,0.43±0.31 vs 18.73±10.53 respectively). Significant reduction in the tissue levels of MDA was noticed in group 1 as compared to group 4, as well as between groups 2 and 4.CONCLUSION: Subcutaneous administration of infliximab reduces the inflammatory activity as well as tissue TNF-α and MDA levels in chemical colitis in rats.Infliximab at a dose of 5 mg/kg BW achieves better histological results and produces higher reduction of the levels of TNF-α than at a dose of 10 mg/kg BW.Infliximab at a dose of 5 mg/kg BW produces

  6. Enterococcus durans TN-3 Induces Regulatory T Cells and Suppresses the Development of Dextran Sulfate Sodium (DSS)-Induced Experimental Colitis

    Science.gov (United States)

    Kanda, Toshihiro; Ohno, Masashi; Imaeda, Hirotsugu; Shimada, Takashi; Inatomi, Osamu; Bamba, Shigeki; Sugimoto, Mitsushige; Andoh, Akira

    2016-01-01

    Background and Aims Probiotic properties of Enterococcus strains have been reported previously. In this study, we investigated the effects of Enterococcus (E.) durans TN-3 on the development of dextran sulfate sodium (DSS) colitis. Methods BALB/c mice were fed with 4.0% DSS in normal chow. Administration of TN-3 (10mg/day) was initiated 7days before the start of DSS feeding. Mucosal cytokine expression was analyzed by real time-PCR and immunohistochemistry. The lymphocyte subpopulation were analyzed by flow cytometry. The gut microbiota profile was analyzed by a terminal-restriction fragment length polymorphism method (T-RFLP). Results The disease activity index and histological colitis score were significantly lower in the DSS plus TN-3 group than in the DSS group. The mucosal mRNA expression of proinflammatory cytokines (IL-1β, IL-6, IL-17A and IFN-γ) decreased significantly in the DSS plus TN-3 group as compared to the DSS group. The proportion of regulatory T cells (Treg cells) in the mucosa increased significantly in the DSS plus TN-3 group as compared to the DSS group. Both fecal butyrate levels and the diversity of fecal microbial community were significantly higher in the TN-3 plus DSS group than in the DSS group. Conclusions E. durans TN-3 exerted an inhibitory effect on the development of DSS colitis. This action might be mediated by the induction of Treg cells and the restoration of the diversity of the gut microbiota. PMID:27438072

  7. IL-33 alleviates DSS-induced chronic colitis in C57BL/6 mice colon lamina propria by suppressing Th17 cell response as well as Th1 cell response.

    Science.gov (United States)

    Zhu, Junfeng; Wang, Yuanyuan; Yang, Fangli; Sang, Lixuan; Zhai, Jingbo; Li, Shengjun; Li, Yan; Wang, Danan; Lu, Changlong; Sun, Xun

    2015-12-01

    Interleukin (IL)-33, a member of the IL-1 cytokine family, is associated with autoimmune diseases including inflammatory bowel diseases (IBD). A few studies on animal models have shown that IL-33 can suppress Th1 cell response and improve Th2 cell response in mesenteric lymph nodes (MLN) and sera. However, there is little data published about the effect of IL-33 on Th17 cell in and Th1/Th2 cell in colon lamina propria. The aim of this study was to investigate the effect of IL-33 on Th17 cell in colon lamina propria of mice with dextran sulfate sodium (DSS) induced chronic colitis. We studied the influence of IL-33 on colonic tissue injury and clinical symptoms of colitis. The T cell subsets were measured by flow cytometry and the production of cytokines secreted by lamina propria lymphocytes (LPL) was measured by Enzyme-Linked Immunosorbent Assay (ELISA) and quantitative real-time PCR. We have found that rIL-33 treatment led to a significant alleviation of DSS induced chronic colitis as evidenced by 1) alleviation of weight loss, DAI, macroscopic changes and histological score; 2) down-regulating the rates and absolute cell numbers of Th17 and Th1 cell in LPL; 3) inducing secretion of lower levels of IFN-γ and IL-17A. It is therefore concluded that IL-33 may play a therapeutic role in DSS-induced chronic colitis in mice by suppressing Th17 response and switching Th1 to Th2 response.

  8. Surgery for Crohn's Disease and Ulcerative Colitis

    Science.gov (United States)

    ... Crohn's Disease & Ulcerative Colitis Go Back Surgery for Crohn's Disease & Ulcerative Colitis Email Print + Share ( Disclaimer: Surgery information ... helps you to learn what to expect. About Crohn’s disease and ulcerative colitis Crohn’s disease and ulcerative colitis ...

  9. Anti-inflammatory effects of Lactobacillus casei BL23 producing or not a manganese-dependant catalase on DSS-induced colitis in mice

    Directory of Open Access Journals (Sweden)

    Corthier Gérard

    2007-07-01

    Full Text Available Abstract Background Human immune cells generate large amounts of reactive oxygen species (ROS throughout the respiratory burst that occurs during inflammation. In inflammatory bowel diseases, a sustained and abnormal activation of the immune system results in oxidative stress in the digestive tract and in a loss of intestinal homeostasis. We previously showed that the heterologous production of the Lactobacillus plantarum ATCC14431 manganese-dependant catalase (MnKat in Lb. casei BL23 successfully enhances its survival when exposed to oxidative stress. In this study, we evaluated the preventive effects of this antioxidative Lb. casei strain in a murine model of dextran sodium sulfate (DSS-induced moderate colitis. Results Either Lb. casei BL23 MnKat- or MnKat+ was administered daily to mice treated with DSS for 10 days. In contrast to control mice treated with PBS for which DSS induced bleeding diarrhea and mucosal lesions, mice treated with both Lb. casei strains presented a significant (p Conclusion No contribution of MnKat to the protective effect from epithelial damage has been observed in the tested conditions. In contrast, these results confirm the high interest of Lb. casei as an anti-inflammatory probiotic strain.

  10. Colitis-inducing potency of CD4+ T cells in immunodeficient, adoptive hosts depends on their state of activation, IL-12 responsiveness, and CD45RB surface phenotype

    DEFF Research Database (Denmark)

    Claesson, M H; Bregenholt, S; Bonhagen, K;

    1999-01-01

    We studied the induction, severity and rate of progression of inflammatory bowel disease (IBD) induced in SCID mice by the adoptive transfer of low numbers of the following purified BALB/c CD4+ T cell subsets: 1) unfractionated, peripheral, small (resting), or large (activated) CD4+ T cells; 2......) fractionated, peripheral, small, or large, CD45RBhigh or CD45RBlow CD4+ T cells; and 3) peripheral IL-12-unresponsive CD4+ T cells from STAT-4-deficient mice. The adoptive transfer into SCID host of comparable numbers of CD4+ T cells was used to assess the colitis-inducing potency of these subsets. Small CD45...... a late-onset IBD manifest > 20 wk posttransfer. In SCID mice with IBD transplanted with IL-12-responsive CD4+ T cells, the colonic lamina propria CD4+ T cells showed a mucosa-seeking memory/effector CD45RBlow Th1 phenotype abundantly producing IFN-gamma and TNF-alpha. In SCID mice transplanted with IL-12...

  11. Degraded carrageenan causing colitis in rats induces TNF secretion and ICAM-1 upregulation in monocytes through NF-kappaB activation.

    Directory of Open Access Journals (Sweden)

    Claudine Benard

    Full Text Available Carrageenan (CGN is a high molecular weight sulphated polysaccharide derived from red seaweeds. In rodents, its degraded forms (dCGN can induce intestinal inflammation associated with macrophage recruitment and activation. The aim of this study was: 1 to analyze the size-dependent effects of dCGN on colon inflammation in vivo, and 2 to correlate these effects with monocyte/macrophage proliferation, cytokine production and expression of various cell surface antigens including ICAM-1 adhesion molecule. Peripheral blood monocytes (PBM and THP-1 monocytic cells were cultured in the presence of either 10 or 40 kDa, dCGN. The 40 kDa, but not the 10 kDa dCGN, induced colitis in in vivo. Degraded CGN inhibited THP-1 cell proliferation in vitro, arresting the cells in G1 phase. In addition, dCGN increased ICAM-1 expression in both PBM and THP-1 cells with a major effect seen after 40 kDa dCGN exposure. Also, dCGN stimulated monocyte aggregation in vitro that was prevented by incubation with anti-ICAM-1 antibody. Finally, dCGN stimulated TNF-alpha expression and secretion by both PBM and THP-1 cells. All these effects were linked to NF-kappaB activation. These data strongly suggest that the degraded forms of CGN have a pronounced effect on monocytes, characteristic of an inflammatory phenotype.

  12. Downregulation of CYP3A and P-glycoprotein in the secondary inflammatory response of mice with dextran sulfate sodium-induced colitis and its contribution to cyclosporine A blood concentrations.

    Science.gov (United States)

    Kawauchi, Shoji; Nakamura, Tsutomu; Miki, Ikuya; Inoue, Jun; Hamaguchi, Tsuneo; Tanahashi, Toshihito; Mizuno, Shigeto

    2014-01-01

    CYP3A and P-glycoprotein (P-gp) play important roles in drug metabolism and excretion; however, their functions in pathological conditions remain unclear. Hepatobiliary abnormalities have been described in patients with ulcerative colitis, which may affect drug metabolism and excretion in the liver and small intestine. We examined the functions of CYP3A and P-gp in the liver and small intestine of mice with dextran sodium sulfate (DSS)-induced colitis. Up to day 7, inflammatory markers were significantly increased in the livers of DSS-treated mice, accompanied by decreased CYP3A. Additionally hepatobiliary transporters and Pregnane X receptor, which regulates the transcriptional activation of CYP3A, were reduced. Both CYP3A and P-gp were significantly decreased in the upper small intestine of DSS-treated mice on day 7. This was associated with the increased expression of inducible nitric oxide synthase, but not changes in nuclear receptor expression. On day 7 of DSS treatment, the concentrations of cyclosporine A (CsA), a substrate of both CYP3A and P-gp, were significantly higher than controls. These results indicated the existence of a second inflammatory response in the liver and upper small intestine of mice with DSS-induced colitis, and bioavailability of CsA was increased by the dysfunction of CYP3A and P-gp in these organs.

  13. Substance P Modulates Colitis-Asscociated Fibrosis

    OpenAIRE

    Koon, Hon Wai; Shih, David; Karagiannides, Iordanes; Zhao, Dezheng; Fazelbhoy, Zafeer; Hing, Tressia; Xu, Hua; Lu, Bao; Gerard, Norma; Pothoulakis, Charalabos

    2010-01-01

    Substance P (SP) and the neurokinin-1 receptor (NK-1R) are involved in the development of colitis and mucosal healing after colonic inflammation. We studied whether SP modulates colonic fibrosis by using a chronic model of trinitrobenzenesulfonic acid (TNBS)-induced colitis in wild-type (WT) and NK-1R-deficient (NK-1R KD) mice. We found increased mRNA expression levels of collagen, vimentin, and the fibrogenic factors transforming growth factor β1 and insulin-like growth factor 1 in the chron...

  14. Prednisolone-appended alpha-cyclodextrin: alleviation of systemic adverse effect of prednisolone after intracolonic administration in 2,4,6-trinitrobenzenesulfonic acid-induced colitis rats.

    Science.gov (United States)

    Yano, H; Hirayama, F; Arima, H; Uekama, K

    2001-12-01

    The titled compound is a cyclodextrin derivative in which prednisolone 21-succinate (PDsuc) is covalently bound to one of the secondary hydroxyl groups of alpha-cyclodextrin (alpha-CyD) via an ester linkage. In this study, the PDsuc-appended alpha-CyD ester conjugate (PDsuc/alpha-CyD conjugate) was intracolonically administered to rats with 2,4,6-trinitrobenzensulfonic acid-induced colitis, and its antiinflammatory and systemic adverse effects were compared with those of prednisolone (PD) alone and the PD/2-hydroxypropyl-beta-CyD complex (PD/HP-beta-CyD complex), which is a noncovalent inclusion complex. Colonic damage score, ratio of distal colon wet weight to body weight, and myeloperoxidase activity were evaluated as measures of the therapeutic effect of PD, whereas the ratio of thymus wet weight to body weight was evaluated as a measure of the side effect of PD. The local antiinflammatory activity increased in the order of PD alone approximately PDsuc/alpha-CyD conjugate keeps the local concentration in the colon at a low but constant level. The results suggest that the PDsuc/alpha-CyD conjugate can alleviate the systemic adverse effect of PD while maintaining the therapeutic activity of PD. This kind of knowledge will be useful in the rational design of steroid prodrugs for the colon-specific drug delivery system. PMID:11745769

  15. Selenium-Containing Phycocyanin from Se-Enriched Spirulina platensis Reduces Inflammation in Dextran Sulfate Sodium-Induced Colitis by Inhibiting NF-κB Activation.

    Science.gov (United States)

    Zhu, Chenghui; Ling, Qinjie; Cai, Zhihui; Wang, Yun; Zhang, Yibo; Hoffmann, Peter R; Zheng, Wenjie; Zhou, Tianhong; Huang, Zhi

    2016-06-22

    Selenium (Se) plays an important role in fine-tuning immune responses. Inflammatory bowel disease (IBD) involves hyperresponsive immunity of the digestive tract, and a low Se level might aggravate IBD progression; however, the beneficial effects of natural Se-enriched diets on IBD remain unknown. Previously, we developed high-yield Se-enriched Spirulina platensis (Se-SP) as an excellent organic nutritional Se source. Here we prepared Se-containing phycocyanin (Se-PC) from Se-SP and observed that Se-PC administration effectively reduced the extent of colitis in mouse induced by dextran sulfate sodium. Supplementation with Se-PC resulted in significant protective effects, including mitigation of body weight loss, bloody diarrhea, and colonic inflammatory damage. The anti-inflammatory effects of Se-PC supplementation were found to involve modulation of cytokines, including IL-6, TNF-α, MCP-1, and IL-10. Mechanistically, Se-PC inhibited the activation of macrophages by suppressing the nuclear translocation of NF-κB, which is involved in the transcription of these pro-inflammatory cytokines. These results together suggest potential benefits of Se-PC as a functional Se supplement to reduce the symptoms of IBD. PMID:27223481

  16. Co-administration of α-lipoic acid and cyclosporine aggravates colon ulceration of acetic acid-induced ulcerative colitis via facilitation of NO/COX-2/miR-210 cascade.

    Science.gov (United States)

    El-Gowelli, Hanan M; Saad, Evan I; Abdel-Galil, Abdel-Galil A; Ibrahim, Einas R

    2015-11-01

    In this work, α-lipoic acid and cyclosporine demonstrated significant protection against acetic acid-induced ulcerative colitis in rats. We proposed that α-lipoic acid and cyclosporine co-administration might modulate their individual effects. Induction of ulcerative colitis in rats was performed by intra-rectal acetic acid (5% v/v) administration for 3 consecutive days. Effects of individual or combined used of α-lipoic acid (35 mg/kg ip) or cyclosporine (5mg/kg sc) for 6 days starting 2 days prior to acetic acid were assessed. Acetic acid caused colon ulceration, bloody diarrhea and weight loss. Histologically, there was mucosal atrophy and inflammatory cells infiltration in submucosa, associated with depletion of colon reduced glutathione, superoxide dismutase and catalase activities and elevated colon malondialdehyde, serum C-reactive protein (C-RP) and tumor necrosis factor-α (TNF-α). Colon gene expression of cyclooxygenase-2 and miR-210 was also elevated. These devastating effects of acetic acid were abolished upon concurrent administration of α-lipoic acid. Alternatively, cyclosporine caused partial protection against acetic acid-induced ulcerative colitis. Cyclosporine did not restore colon reduced glutathione, catalase activity, serum C-RP or TNF-α. Unexpectedly, co-administration of α-lipoic acid and cyclosporine aggravated colon ulceration. Concomitant use of α-lipoic acid and cyclosporine significantly increased nitric oxide production, cyclooxygenase-2 and miR-210 gene expression compared to all other studied groups. The current findings suggest that facilitation of nitric oxide/cyclooxygenase-2/miR-210 cascade constitutes, at least partially, the cellular mechanism by which concurrent use of α-lipoic acid and cyclosporine aggravates colon damage. Collectively, the present work highlights the probable risk of using α-lipoic acid/cyclosporine combination in ulcerative colitis patients.

  17. Genetics Home Reference: ulcerative colitis

    Science.gov (United States)

    ... my area? Other Names for This Condition colitis gravis idiopathic proctocolitis inflammatory bowel disease, ulcerative colitis type ... for professional medical care or advice. Users with questions about a personal health condition should consult with ...

  18. Non-IBD and noninfectious colitis

    DEFF Research Database (Denmark)

    Nielsen, Ole Haagen; Vainer, Ben; Rask-Madsen, Jørgen

    2008-01-01

    A wide range of etiologies and pathogenic mechanisms underlie colitis. This Review provides an overview of the pathophysiology, epidemiology, histopathology, and clinical characteristics of noninfectious and non-IBD forms of colitis: microscopic colitis, Behçet's syndrome, diversion colitis......, diverticular colitis, eosinophilic colitis, ischemic colitis, and radiation colitis. These more recently characterized and rare forms of colitis occur as either primary conditions or complications of other diseases. Most of these diseases are uncommon; therefore, epidemiologic data and data from controlled...... trials are not readily available. Practical guidelines for the diagnosis and therapy of these more recently characterized and rarer forms of colitis are given where possible....

  19. Non-IBD and noninfectious colitis

    DEFF Research Database (Denmark)

    Nielsen, O.H.; Vainer, B.; Rask-Madsen, J.

    2008-01-01

    A wide range of etiologies and pathogenic mechanisms underlie colitis. This Review provides and overview of the pathophysiology, epidemiology, histopathology, and clinical characteristics of noninfectious and non-IBD forms of colitis: microscopic colitis, Behcet's syndrome, diversion colitis......, diverticular colitis, eosinophilic colitis, ischemic colitis, and radiation colitis. These more recently characterized and rare forms of colitis occur as either primary conditions or complications of other diseases. Most of these diseases are uncommon; therefore, epidemiologic data and data from controlled...... trials are not readily available. Practical guidelines for the diagnosis and therapy of these more recently characterized and rarer forms of colitis are given where possible Udgivelsesdato: 2008/1...

  20. Acute and subacute chemical-induced lung injuries: HRCT findings

    Energy Technology Data Exchange (ETDEWEB)

    Akira, Masanori, E-mail: Akira@kch.hosp.go.jp [Department of Radiology, National Hospital Organization Kinki-Chuo Chest Medical Center, 1180 Nagasone-cho, Kita-ku, Sakai City, Osaka 591-8555 (Japan); Suganuma, Narufumi [Department of Environmental Medicine, Kochi Medical School (Japan)

    2014-08-15

    Lung injury caused by chemicals includes bronchitis, bronchiolitis, chemical pneumonitis, pulmonary edema, acute respiratory distress syndrome, organizing pneumonia, hypersensitivity pneumonitis, acute eosinophilic pneumonia, and sarcoid-like granulomatous lung disease. Each chemical induces variable pathophysiology and the situation resembles to the drug induced lung disease. The HRCT features are variable and nonspecific, however HRCT may be useful in the evaluation of the lung injuries and so we should know about HRCT features of lung parenchymal abnormalities caused by chemicals.

  1. Acute and subacute chemical-induced lung injuries: HRCT findings

    International Nuclear Information System (INIS)

    Lung injury caused by chemicals includes bronchitis, bronchiolitis, chemical pneumonitis, pulmonary edema, acute respiratory distress syndrome, organizing pneumonia, hypersensitivity pneumonitis, acute eosinophilic pneumonia, and sarcoid-like granulomatous lung disease. Each chemical induces variable pathophysiology and the situation resembles to the drug induced lung disease. The HRCT features are variable and nonspecific, however HRCT may be useful in the evaluation of the lung injuries and so we should know about HRCT features of lung parenchymal abnormalities caused by chemicals

  2. Chemically induced compaction bands in geomaterials

    Science.gov (United States)

    Stefanou, Ioannis; Sulem, Jean

    2013-04-01

    Compaction bands play an important role in oil production and may provide useful information on various geological processes. Various mechanisms can be involved at different scales: the micro scale (e.g. the grain scale), the meso scale (e.g. the Representative Element Volume) and the macro scale (e.g. the structure). Moreover, hydro-chemo-mechanical couplings might play an important role in triggering instabilities in the form of compaction bands. Compaction bands can be seen as an instability of the underneath mathematical problem leading to localization of deformation [1,2,3]. Here we explore the conditions of compaction banding in quartz-based geomaterials by considering the effect of chemical dissolution and precipitation [4,5]. In due course of the loading process grain crushing affects the residual strength, the porosity and the permeability of the material. Moreover, at the micro-level, grain crushing results in an increase of the grain specific surface, which accelerates the dissolution [6]. Consequently, the silica is removed more rapidly from the grain skeleton and the overall mechanical properties are degraded due to chemical factors. The proposed model accounts for these phenomena. In particular, the diffusion of the diluted in the water silica is considered through the mass balance equation of the porous medium. The reduction of the mechanical strength of the material is described through a macroscopic failure criterion with chemical softening. The grain size reduction is related to the total energy input [7]. A grain size and porosity dependent permeability law is adopted. These degradation mechanisms are coupled with the dissolution/precipitation reaction kinetics. The obtained hydro-chemo-mechanical model is used to investigate the conditions, the material parameters and the chemical factors inducing compaction bands formation. References [1] J.W. Rudnicki, and J.R. Rice. "Conditions for the Localization of Deformation in Pressure

  3. Acute Onset Collagenous Colitis with Unique Endoscopic Findings

    Directory of Open Access Journals (Sweden)

    Rintaro Moroi

    2014-01-01

    Full Text Available We experienced a rare case of 72-year-old woman with acute onset collagenous colitis (CC induced by lansoprazole. The patient developed acute abdominal pain, watery diarrhea, and melena that are quite rare in usual CC. We could find the characteristic colonoscopic findings such as active long liner ulcers in the patient. We also observed the healing courses of these unique findings. Our case indicates two important points of view. (1 CC sometimes develops with acute onset symptoms which resemble those of ischemic colitis. (2 Colonoscopy would be useful and necessary to distinguish acute onset CC and ischemic colitis.

  4. Eosinophilic colitis in infants

    Directory of Open Access Journals (Sweden)

    Adriana Chebar Lozinsky

    2014-01-01

    Full Text Available OBJECTIVE: To review the literature for clinical data on infants with allergic or eosinophilic colitis. DATA SOURCE: MEDLINE search of all indexes was performed using the words ''colitis or procto-colitis and eosinophilic'' or ''colitis or proctocolitis and allergic'' between 1966 and February of 2013. All articles that described patients' characteristics were selected. DATA SYNTHESIS: A total of 770 articles were identified, of which 32 met the inclusion criteria. The 32 articles included a total of 314 infants. According to the available information, 61.6% of infants were male and 78.6% were younger than 6 months. Of the 314 patients, 49.0% were fed exclusively breast milk, 44.2% received cow's milk protein, and 6.8% received soy protein. Diarrheal stools were described in 28.3% of patients. Eosinophilia was found in 43.8% (115/263 of infants. Colonic or rectal biopsy showed infiltration by eosinophils (between 5 and 25 perhigh-power field in 89.3% (236/264 of patients. Most patients showed improvement with theremoval of the protein in cow's milk from their diet or the mother's diet. Allergy challenge tests with cow's milk protein were cited by 12 of the 32 articles (66 patients. CONCLUSIONS: Eosinophilic colitis occurs predominantly in the first six months of life and in males. Allergy to cow's milk was considered the main cause of eosinophilic colitis. Exclusion of cow'smilk from the diet of the lactating mother or from the infant's diet is generally an effective therapeutic measure.

  5. Ferrous sulfate, but not iron polymaltose complex, aggravates local and systemic inflammation and oxidative stress in dextran sodium sulfate-induced colitis in rats

    Directory of Open Access Journals (Sweden)

    Toblli JE

    2015-05-01

    Full Text Available Jorge E Toblli, Gabriel Cao, Margarita Angerosa Laboratory of Experimental Medicine, Hospital Alemán, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina Background and aims: Iron deficiency is common in inflammatory bowel disease, yet oral iron therapy may worsen the disease symptoms and increase systemic and local oxidative stress. The aim of this study was to compare the effects of oral ferrous sulfate and iron polymaltose complex on inflammatory and oxidative stress markers in colitic rats.Methods: Animals were divided into four groups with ten animals each. Rats of three groups received dextran sodium sulfate to induce colitis and animals of two of these groups received 5 mg iron/kg of body weight a day, as ferrous sulfate or iron polymaltose complex, for 7 days. Gross colon anatomy, histology of colon and liver, stainings of L-ferritin, Prussian blue, hepcidin, tumor necrosis factor-α, and interleukin-6, as well serum levels of liver enzymes, inflammatory markers, and iron markers, were assessed.Results: Body weight, gross anatomy, crypt injury and inflammation scores, inflammatory parameters in liver and colon, as well as serum and liver hepcidin levels were not significantly different between colitic animals without iron treatment and colitic animals treated with iron polymaltose complex. In contrast, ferrous sulfate treatment caused significant worsening of these parameters. As opposed to ferrous sulfate, iron polymaltose complex caused less or no additional oxidative stress in the colon and liver compared to colitic animals without iron treatment.Conclusion: Iron polymaltose complex had negligible effects on colonic tissue erosion, local or systemic oxidative stress, and local or systemic inflammation, even at high therapeutic doses, and may thus represent a valuable oral treatment of iron deficiency in inflammatory bowel disease. Keywords: preclinical, oral iron treatment, tolerability, colonic tissue erosion

  6. Dextran sodium sulfate-induced colitis leads to bone loss in mice%葡聚糖硫酸钠诱导的小鼠肠炎中骨质丢失的分析

    Institute of Scientific and Technical Information of China (English)

    魏凡华; 胡志华

    2014-01-01

    建立小鼠葡聚糖硫酸钠肠炎(DSS)模型,并分析肠炎小鼠中骨质丢失的发生情况.C57BL/6小鼠口服DSS溶液2周以建立肠炎模型,第1周饮用2% DSS溶液,第2周饮用1% DSS溶液.饮用蒸馏水的C57BL/6小鼠作为对照.记录每组小鼠体质量变化,观察粪便和血便状况,μCT分析股骨骨质丢失的情况.结果表明DSS处理组小鼠和对照组相比,出现了明显的骨质丢失,骨量减少,骨小梁数目下降.说明DSS诱导的小鼠肠炎模型可以作为研究肠炎引发骨质丢失的良好模型.%To establish a colitis model induced by dextran sodium sulfate (DSS) and analyzed bone loss in colitic mice. Colitis was induced by administration of DSS solution for 2 weeks, 2%DSS and 1%DSS solution was administrated on the first week and second week, respectively. Body weight, stool and blood score of each group mice was recorded, and femoral bone loss were examined by micro computed tomography (μCT). The results demonstrate that DSS-treated mice exhibited a lower bone mass and decreased trabecular numbers as compared with the controls. Collectively, DSS-induced colitis model can be used to study pharmacological interventions for bone loss in mice.

  7. 氟尿嘧啶致结肠炎及手足综合征%Fluorouracil-induced colitis and hand-foot syndrome

    Institute of Scientific and Technical Information of China (English)

    徐莉; 张玉洁; 冯娟; 董涛; 王飙落; 梁洁; 吴开春

    2015-01-01

    A 48-year-old female patient with abdominal pain was diagnosed as"acute pancreatitis"at the local hospital and received IV infusion of fluorouracil 1. 0 g,pantoprazole sodium 120 mg and amino acid(18AA)250 ml once daily. On day 11 of treatments,she developed mucous bloody stool with tenesmus,fever with alopecia, and exfoliative changes of her hand-foot skin. Ulcerative colitis was considered. Drugs above mentioned were stopped and glucocorticoid treatment was given. After 3 months of hormone treatment,her mucous bloody stool relieved,the abdominal pain exacerbated,and alopecia and hand-foot damages was not improved. Then,she came to Xijing Hospital. Pathological examination of living tissue in colonic mucosa showed no crypt structure changes. According to the patient's history,changes of hair and hand-foot skin,and her pathological examination results,the drug-induced colitis and hand-foot syndrome was considered. The dosage of glucocorticoid was gradually reduced and stopped at last. Propylamine acyl glutamine was given to repair the intestinal mucosa and keep the balance of the gut bacteria and intestinal nutrition,metronidazole for anti-infection,and enteral nutrition for supportive treatments. After 5 days of treatments,the patient's symptoms of abdominal pain and mucous bloody stool relieved,hair loss and skin damage recovered gradually. At 4 months of follow up,abdominal pain and bloody stool did not recur and her hair and skin returned to normal.%1例48岁女性患者因腹痛在当地医院以“急性胰腺炎”给予5-氟尿嘧啶(1.0 g)、泮托拉唑(120 mg)和复方氨基酸注射液(18AA)(250 ml)静脉滴注,均1次/d。治疗第11天出现黏液血便伴里急后重、发热伴脱发及手足皮肤剥脱样改变,考虑“溃疡性结肠炎”,停用上述3种药物给予激素治疗。治疗近3个月,血便减少但腹痛加重,脱发及手足皮肤损害无改善,遂转入西京医院。结肠黏膜活体组织病

  8. Acetylsalicylic Acid Reduces the Severity of Dextran Sodium Sulfate-Induced Colitis and Increases the Formation of Anti-Inflammatory Lipid Mediators

    Directory of Open Access Journals (Sweden)

    Thomas Köhnke

    2013-01-01

    Full Text Available The role of non-steroidal anti-inflammatory drugs in inflammatory bowel disease is controversial, as they have been implicated in disease aggravation. Different from other cyclooxygenase inhibitors, acetylsalicylic acid (ASA enhances the formation of anti-inflammatory and proresolution lipoxins derived from arachidonic acid as well as resolvins from omega-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA. In this study, we examined the effect of ASA on murine dextran sodium sulfate colitis. A mouse magnetic resonance imaging (MRI protocol and post mortem assessment were used to assess disease severity, and lipid metabolites were measured using liquid chromatography-coupled tandem mass spectrometry. Decreased colitis activity was demonstrated by phenotype and MRI assessment in mice treated with ASA, and confirmed in postmortem analysis. Analysis of lipid mediators showed sustained formation of lipoxin A4 and an increase of DHA-derived 17-hydroxydocosahexaenoic acid (17-HDHA after treatment with ASA. Furthermore, in vitro experiments in RAW264.7 murine macrophages demonstrated significantly increased phagocytosis activity after incubation with 17-HDHA, supporting its proresolution effect. These results show a protective effect of ASA in a murine colitis model and could give a rationale for a careful reassessment of ASA therapy in patients with inflammatory bowel disease and particularly ulcerative colitis, possibly combined with DHA supplementation.

  9. NCX-1015, a nitric-oxide derivative of prednisolone, enhances regulatory T cells in the lamina propria and protects against 2,4,6-trinitrobenzene sulfonic acid-induced colitis in mice

    Science.gov (United States)

    Fiorucci, Stefano; Antonelli, Elisabetta; Distrutti, Eleonora; Del Soldato, Piero; Flower, Roderick J.; Clark, Mark J. Paul; Morelli, Antonio; Perretti, Mauro; Ignarro, Louis J.

    2002-01-01

    NCX-1015 is a nitric oxide (NO)-releasing derivative of prednisolone. In this study we show NCX-1015 protects mice against the S. A. development and induces healing of T helper cell type 1-mediated experimental colitis induced by intrarectal administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS). The beneficial effect of NCX-1015 was reflected in increased survival rates, improvement of macroscopic and histologic scores, a decrease in the mucosal content of T helper cell type 1 cytokines (protein and mRNA), and diminished myeloperoxidase activity in the colon. In contrast to its NO derivative, only very high doses of prednisolone were effective in reproducing these beneficial effects. NCX-1015 was 10- to 20-fold more potent than the parent compound in inhibiting IFN-γ secretion by lamina propria mononuclear cells. Protection against developing colitis correlated with inhibition of nuclear translocation of p65/Rel A in these cells. In vivo treatment with NCX-1015 potently stimulated IL-10 production, suggesting that the NO steroid induces a regulatory subset of T cells that negatively modulates intestinal inflammation. PMID:12427966

  10. N'-[(3-[benzyloxy]benzylidene]-3,4,5-trihydroxybenzohydrazide (1) protects mice against colitis induced by dextran sulfate sodium through inhibiting NFκB/IL-6/STAT3 pathway.

    Science.gov (United States)

    Xi, Meiyang; Wang, Xiaojian; Ge, Jun; Yin, Dali

    2016-08-19

    IBD has attracted much attention for its negative influence on the quality of life and increased risk of colorectal cancer. In this study, we discovered the inhibitory activity of the polyphenol compound (1) in DSS induced colitis in mice by targeting NFκB/IL-6/STAT3 pathway. This compound effectively protected against body weight loss and colon length shortening induced by DSS. Additionally, 1 inhibited DSS induced damage in colon, notably decreasing the severity of inflammation, the extent of inflammation, crypt damage and percent involvement. The production of inflammatory mediators of IL-6 and COX-2 was also significantly attenuated when treated with 1. It may be attributed to inhibiting NFκB signaling. Moreover, this polyphenol suppressed p-STAT3 production as well as its downstream proteins response for apoptosis, such as Bcl-2 and Bax. In summary, the study not only afforded our understanding involved in colitis, but also provided the possible therapy for human with IBD. PMID:27311853

  11. Crohn's Disease and Ulcerative Colitis: Emotional Factors

    Science.gov (United States)

    ... Ulcerative Colitis: Emotional Factors Q & A Go Back Crohn’s Disease and Ulcerative Colitis: Emotional Factors Q & A Email ... WHAT IS THE CAUSE OF ULCERATIVE COLITIS AND CROHN’S DISEASE? The origin of IBD is still unknown. It ...

  12. Chemically induced intestinal damage models in zebrafish larvae.

    Science.gov (United States)

    Oehlers, Stefan H; Flores, Maria Vega; Hall, Christopher J; Okuda, Kazuhide S; Sison, John Oliver; Crosier, Kathryn E; Crosier, Philip S

    2013-06-01

    Several intestinal damage models have been developed using zebrafish, with the aim of recapitulating aspects of human inflammatory bowel disease (IBD). These experimentally induced inflammation models have utilized immersion exposure to an array of colitogenic agents (including live bacteria, bacterial products, and chemicals) to induce varying severity of inflammation. This technical report describes methods used to generate two chemically induced intestinal damage models using either dextran sodium sulfate (DSS) or trinitrobenzene sulfonic acid (TNBS). Methods to monitor intestinal damage and inflammatory processes, and chemical-genetic methods to manipulate the host response to injury are also described.

  13. Cellular localization, binding sites, and pharmacologic effects of TFF3 in experimental colitis in mice

    DEFF Research Database (Denmark)

    Kjellev, Stine; Thim, Lars; Pyke, Charles;

    2007-01-01

    the effect of TFF3 on dextrane sulfate sodium (DSS)-induced colitis in mice. Expression of endogenous TFF1-3 was examined by in situ hybridization and immunohistochemistry, and the distribution of intravenously, intraperitoneally, and subcutaneously administered (125)I-TFF3 by autoradiography and gamma......-counting. The effect of systemically administered TFF3 on DSS-induced colitis was assessed. We found increased expression of endogenous TFF3 and increased binding of injected (125)I-TFF3 in the colon of animals with DSS-induced colitis. The distribution of intraperitoneally and subcutaneously administered (125)I-TFF3...... was comparable. Systemic administration of the peptides reduced the severity of colitis. Expression of endogenous TFF3 and binding of systemically administered TFF3 are increased in DSS-induced colitis. Systemic administration of TFF3 attenuates the disease. These findings suggest a role of TFF3 in mucosal...

  14. American ginseng attenuates azoxymethane/dextran sodium sulfate-induced colon carcinogenesis in mice

    OpenAIRE

    Yu, Chunhao; Wen, Xiao-Dong; Zhang, Zhiyu; Zhang, Chun-Feng; Wu, Xiao-hui; Martin, Adiba; Du, Wei; He, Tong-Chuan; Wang, Chong-Zhi; Yuan, Chun-Su

    2014-01-01

    Background Colorectal cancer is a leading cause of cancer-related death, and inflammatory bowel disease is a risk factor for this malignancy. We previously reported colon cancer chemoprevention potential using American ginseng (AG) in a xenograft mice model. However, the nude mouse model is not a gut-specific colon carcinogenesis animal model. Methods In this study, an experimental colitis and colitis-associated colorectal carcinogenesis mouse model, chemically induced by azoxymethane/dextran...

  15. Radiation-induced chemical evolution of biomolecules

    International Nuclear Information System (INIS)

    Chemical evolution in glycilglycine (Gly2) films irradiated with 146 nm vacuum ultraviolet light was studied. It is found that quantum efficiency of chemical evolution from Gly2 to glycilglycilglycine (Gly3) is smaller than that to glycilglycilglycilglycine (Gly4) due to the multiple step of reaction. Furthermore, we have carried out measurement of soft X-ray natural circular dichroism spectra for serine and alanine films in the energy region of oxygen 1s transition and we report the splitting of 1s→π* transitions.

  16. Clostridium difficile Colitis

    OpenAIRE

    Trudel, Judith L.

    2007-01-01

    Clostridium difficile enterocolitis is endemic in most modern hospitals. The spectrum of clinical presentation varies from the asymptomatic carrier state to fulminant colitis with toxic megacolon and perforation. Highly toxigenic and lethal strains of C. difficile have emerged worldwide. Medical treatment consists of discontinuing the precipitating antibiotic, supportive measures and bowel rest, and antibiotic treatment with metronidazole or vancomycin. Surgical treatment may be necessary in ...

  17. Therapeutic Effect of Oridonin Tablet on Acetic Acid-induced Ulcerative Colitis in Mice%冬凌草甲素片对醋酸诱导的小鼠溃疡性结肠炎的治疗作用

    Institute of Scientific and Technical Information of China (English)

    臧凯宏; 杜丽东; 刘晓梅; 马骏; 任远

    2012-01-01

    目的 考察冬凌草甲素片口服给药对醋酸诱导的小鼠溃疡性结肠炎的治疗作用.方法 醋酸诱导的溃疡性结肠炎小鼠分别给予不同剂量的冬凌草甲素片灌胃给药,给药7d后,考察冬凌草甲素片对溃疡性结肠炎小鼠病变活动(体质量、便潜血及粪便性状)的影响,以及对结肠病理组织学变化,结肠髓过氧化物酶活性及胸腺和脾脏指数的影响.结果 冬凌草甲素片口服给药可剂量依赖性的降低结肠炎小鼠的病变活动、减轻结肠炎症、降低髓过氧化物酶活性,改善免疫器官脏器指数,以冬凌草甲素片高剂量给药组的作用更为显著.结论 高剂量冬凌草甲素片口服给药对醋酸诱导的小鼠溃疡性结肠炎具有治疗作用,其机制可能与冬凌草甲素的抗炎和免疫调节作用有关.%OBJECTIVE To investigate the therapeutic effect of Oridonin tablet on acetic acid-induced ulcerative colitis in mice.METHODS Oridonin tablets at different dosages were administered orally to acetic acid-induced colitis mice.After 7 days of treatment,the effects of Oridonin tablet on disease activity (i.e.body weight,stool blood,and stool consistency),colonic macroscopic and histological score,myleoperoxidase activity,and thymic and splenic indexes were evaluated in acetic acid-induced ulcerative colitis in mice.RESULTS Oridonin tablet treatment dose-dependently reduced the disease activity,attenuated colonic inflammation and myleoperoxidase activity,and improved the thymic and splenic indexes in acetic acid-induced ulcerative colitis in mice,especially in high dose of Oridonin tablet treated group.CONCLUSION High dose of Oridonin tablet treatment shows therapeutic effect on acetic acid-induced ulcerative colitis in mice,the underlying mechanism may have close correlation with its anti-inflammatory and immune regulatory effects.

  18. 75 FR 76460 - Lymphohematopoietic Cancers Induced by Chemicals and Other Agents: Overview and Implications for...

    Science.gov (United States)

    2010-12-08

    ... AGENCY Lymphohematopoietic Cancers Induced by Chemicals and Other Agents: Overview and Implications for..., ``Lymphohematopoietic Cancers Induced by Chemicals and Other Agents: Overview and Implications for Risk Assessment.... ADDRESSES: The draft ``Lymphohematopoietic Cancers Induced by Chemicals and Other Agents: Overview...

  19. Colitis associated with biological agents

    Institute of Scientific and Technical Information of China (English)

    Hugh James Freeman

    2012-01-01

    In the past,there has been considerable focus on a host of drugs and chemicals that may produce colonic toxicity.Now,a variety of new biological monoclonal antibody agents,usually administered by infusion,have appeared in the clinical realm over the last decade or so to treat different chronic inflammatory or malignant disorders.For some of these agents,adverse effects have been documented,including apparently new forms of immune-mediated inflammatory bowel disease.In some,only limited symptoms have been recorded,but in others,severe colitis with serious complications,such as bowel perforation has been recorded.In others,adverse effects may have a direct vascular or ischemic basis,while other intestinal effects may be related to a superimposed infection.Some new onset cases of ulcerative colitis or Crohn's disease may also be attributed to the same agents used to treat these diseases,or be responsible for disease exacerbation.Dramatic and well documented side effects have been observed with ipilimumab,a humanized monoclonal antibody developed to reduce and overcome cytotoxic T-lymphocyte antigen 4,a key negative feedback regulator of the T-cell anti-tumor response.This agent has frequently been used in the treatment of different malignancies,notably,malignant melanoma.Side effects with this agent occur in up to 40% and these are believed to be largely immune-mediated.One of these is a form of enterocolitis that may be severe,and occasionally,fatal.Other agents include rituximab (an antiCD20 monoclonal antibody),bevacizumab (a monoclonal antibody against the vascular endothelial growth factor) and anti-tumor necrosis factor agents,including infliximab,adalimumab and etanercept.

  20. Ileal pouch surgery for ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Simon P Bach; Neil J Mortensen

    2007-01-01

    Ulcerative colitis (UC) is a relapsing and remitting disease characterised by chronic mucosal and submucosal inflammation of the colon and rectum.Treatment may vary depending upon the extent and severity of inflammation. Broadly speaking medical treatments aim to induce and then maintain remission.Surgery is indicated for inflammatory disease that is refractory to medical treatment or in cases of neoplastic transformation. Approximately 25% of patients with UC ultimately require colectomy. Ileal pouch-anal anastomosis (IPAA) has become the standard of care for patients with ulcerative colitis who ultimately require colectomy. This review will examine indications for IPAA, patient selection, technical aspects of surgery,management of complications and long term outcome following this procedure.

  1. Anti-inflammatory effects of methanolic extract of green algae Caulerpa mexicana in a murine model of ulcerative colitis

    Directory of Open Access Journals (Sweden)

    Mariana A.O. Bitencourt

    2015-12-01

    Full Text Available Abstract Inflammatory bowel diseases, which include Crohn's disease and ulcerative colitis, are characterized by chronic and relapsed gut inflammation. Caulerpa mexicana is a type of green marine algae that can be found in tropical areas, such as the Brazilian Coastland. These macrophytes exhibit in vitro and in vivo anti-inflammatory properties such as the ability to reduce both cell migration to different sites and edema formation induced by chemical irritants. The aim of this study was to examine the effect of the C. mexicana methanolic extract on the treatment of colitis induced by dextran sodium sulfate. Acute experimental colitis was induced in BALB/c mice by treatment with 3% dextran sodium sulfate orally for 14 days. During this 14-day period, C. mexicana methanolic extract (2 mg/kg/day was given intravenously on alternate days. Treatment with the methanolic extract significantly attenuated body weight loss and severe clinical symptoms. This was associated with a remarkable amelioration of colonic architecture disruption and a significant reduction in pro-inflammatory cytokine production. These results suggest that the anti-inflammatory action of C. mexicana methanolic extract on colorectal sites may be a useful therapeutic approach for inflammatory bowel diseases.

  2. CD4+CD25- T cells that express latency-associated peptide on the surface suppress CD4+CD45RBhigh-induced colitis by a TGF-beta-dependent mechanism.

    Science.gov (United States)

    Oida, Takatoku; Zhang, Xingmin; Goto, Masao; Hachimura, Satoshi; Totsuka, Mamoru; Kaminogawa, Shuichi; Weiner, Howard L

    2003-03-01

    Murine CD4(+)CD25(+) regulatory cells have been reported to express latency-associated peptide (LAP) and TGF-beta on the surface after activation, and exert regulatory function by the membrane-bound TGF-beta in vitro. We have now found that a small population of CD4(+) T cells, both CD25(+) and CD25(-), can be stained with a goat anti-LAP polyclonal Ab without being stimulated. Virtually all these LAP(+) cells are also positive for thrombospondin, which has the ability to convert latent TGF-beta to the active form. In the CD4(+)CD45RB(high)-induced colitis model of SCID mice, regulatory activity was exhibited not only by CD25(+)LAP(+) and CD25(+)LAP(-) cells, but also by CD25(-)LAP(+) cells. CD4(+)CD25(-)LAP(+) T cells were part of the CD45RB(low) cell fraction. CD4(+)CD25(-)LAP(-)CD45RB(low) cells had minimal, if any, regulatory activity in the colitis model. The regulatory function of CD25(-)LAP(+) cells was abrogated in vivo by anti-TGF-beta mAb. These results identify a new TGF-beta-dependent regulatory CD4(+) T cell phenotype that is CD25(-) and LAP(+). PMID:12594277

  3. The Rhizome Mixture of Anemarrhena asphodeloides and Coptis chinensis Attenuates Mesalazine-Resistant Colitis in Mice

    Directory of Open Access Journals (Sweden)

    Su-Min Lim

    2016-01-01

    Full Text Available We investigated the effect of DWac on the gut microbiota composition in mice with 2,3,6-trinitrobenzenesulfonic acid- (TNBS- induced colitis. Treatment with DWac restored TNBS-disturbed gut microbiota composition and attenuated TNBS-induced colitis. Moreover, we examined the effect of DWac in mice with mesalazine-resistant colitis (MRC. Intrarectal injection of TNBS in MRC mice caused severe colitis, as well as colon shortening, edema, and increased myeloperoxidase activity. Treatment with mesalazine (30 mg/kg did not attenuate TNBS-induced colitis in MRC mice, whereas treatment with DWac (30 mg/kg significantly attenuated TNBS-induced colitis. Moreover, treatment with the mixture of mesalazine (15 mg/kg and DWac (15 mg/kg additively attenuated colitis in MRC mice. Treatment with DWac and its mixture with mesalazine inhibited TNBS-induced activation of NF-κB and expression of M1 macrophage markers but increased TNBS-suppressed expression of M2 macrophage markers. Furthermore, these inhibited TNBS-induced T-bet, RORγt, TNF-α, and IL-17 expression but increased TNBS-suppressed Foxp3 and IL-10 expression. However, Th2 cell differentiation and GATA3 and IL-5 expression were not affected. These findings suggest that DWac can ameliorate MRC by increasing the polarization of M2 macrophage and correcting the disturbance of gut microbiota and Th1/Th17/Treg, as well as additively attenuating MRC along with mesalazine.

  4. Tofacitinib in ulcerative colitis.

    Science.gov (United States)

    Archer, Thomas P; Moran, Gordon W; Ghosh, Subrata

    2016-05-01

    Cytokines orchestrate immune and inflammatory responses involved in the pathogenesis of ulcerative colitis (UC). Protein kinases are essential for signal transduction in eukaryotic cells. Janus kinases (JAKs) are a family of protein tyrosine kinases that play a pivotal role in cytokine receptor signaling. Indeed, a major subgroup of cytokines use Type I and II cytokine receptors which signal via the activation of JAKs. Tofacitinib is an oral JAK inhibitor that has been studied in autoimmune pathologies, including UC and rheumatoid arthritis with good overall efficacy and acceptable safety profile. This literature review was performed with the goal of summarizing the knowledge on JAK inhibitors in UC treatment. PMID:27140405

  5. Characterization of T-regulatory cells, induced by immature dendritic cells, which inhibit enteroantigen-reactive colitis-inducing T-cell responses in vitro and in vivo

    DEFF Research Database (Denmark)

    Gad, Monika; Kristensen, Nanna N; Kury, Evelyn;

    2004-01-01

    Regulatory T (Treg) cells, derived from co-cultures of unfractionated CD4(+) T cells and immature dendritic cells (DC), suppress enteroantigen-induced proliferation of CD4(+) CD25(-) T cells. The DC-induced Treg cells are a mixture of CD25(+) (10-20%) and CD25(-) (80-90%) T cells. However, all the...... suppressor activity in vitro and in vivo resides in the CD25(+) T-cell subset. The CD25(+) DC-induced Treg cells can inhibit enteroantigen-induced proliferation in vitro through a transwell membrane, and their function does not appear to depend on previous activation. DC-induced CD25(+) Treg cells display a...... naive phenotype, expressing high levels of CD45RB and l-selectin (CD62L). In addition, the DC-induced Treg cells mediate a stronger suppressive activity than prototype CD25(+) regulatory T cells. The DC-induced Treg cells, and hereof purified CD25(+) and CD25(-) T-cell fractions, were co-injected into...

  6. Combined NADPH oxidase 1 and interleukin 10 deficiency induces chronic endoplasmic reticulum stress and causes ulcerative colitis-like disease in mice.

    Science.gov (United States)

    Tréton, Xavier; Pedruzzi, Eric; Guichard, Cécile; Ladeiro, Yannick; Sedghi, Shirin; Vallée, Mélissa; Fernandez, Neike; Bruyère, Emilie; Woerther, Paul-Louis; Ducroc, Robert; Montcuquet, Nicolas; Freund, Jean-Noel; Van Seuningen, Isabelle; Barreau, Frédérick; Marah, Assiya; Hugot, Jean-Pierre; Cazals-Hatem, Dominique; Bouhnik, Yoram; Daniel, Fanny; Ogier-Denis, Eric

    2014-01-01

    Ulcerative colitis (UC) is a chronic inflammatory bowel disease affecting the rectum which progressively extents. Its etiology remains unknown and the number of treatments available is limited. Studies of UC patients have identified an unbalanced endoplasmic reticulum (ER) stress in the non-inflamed colonic mucosa. Animal models with impaired ER stress are sensitive to intestinal inflammation, suggesting that an unbalanced ER stress could cause inflammation. However, there are no ER stress-regulating strategies proposed in the management of UC partly because of the lack of relevant preclinical model mimicking the disease. Here we generated the IL10/Nox1dKO mouse model which combines immune dysfunction (IL-10 deficiency) and abnormal epithelium (NADPH oxidase 1 (Nox1) deficiency) and spontaneously develops a UC-like phenotype with similar complications (colorectal cancer) than UC. Our data identified an unanticipated combined role of IL10 and Nox1 in the fine-tuning of ER stress responses in goblet cells. As in humans, the ER stress was unbalanced in mice with decreased eIF2α phosphorylation preceding inflammation. In IL10/Nox1dKO mice, salubrinal preserved eIF2α phosphorylation through inhibition of the regulatory subunit of the protein phosphatase 1 PP1R15A/GADD34 and prevented colitis. Thus, this new experimental model highlighted the central role of epithelial ER stress abnormalities in the development of colitis and defined the defective eIF2α pathway as a key pathophysiological target for UC. Therefore, specific regulators able to restore the defective eIF2α pathway could lead to the molecular remission needed to treat UC. PMID:25014110

  7. Combined NADPH oxidase 1 and interleukin 10 deficiency induces chronic endoplasmic reticulum stress and causes ulcerative colitis-like disease in mice.

    Directory of Open Access Journals (Sweden)

    Xavier Tréton

    Full Text Available Ulcerative colitis (UC is a chronic inflammatory bowel disease affecting the rectum which progressively extents. Its etiology remains unknown and the number of treatments available is limited. Studies of UC patients have identified an unbalanced endoplasmic reticulum (ER stress in the non-inflamed colonic mucosa. Animal models with impaired ER stress are sensitive to intestinal inflammation, suggesting that an unbalanced ER stress could cause inflammation. However, there are no ER stress-regulating strategies proposed in the management of UC partly because of the lack of relevant preclinical model mimicking the disease. Here we generated the IL10/Nox1dKO mouse model which combines immune dysfunction (IL-10 deficiency and abnormal epithelium (NADPH oxidase 1 (Nox1 deficiency and spontaneously develops a UC-like phenotype with similar complications (colorectal cancer than UC. Our data identified an unanticipated combined role of IL10 and Nox1 in the fine-tuning of ER stress responses in goblet cells. As in humans, the ER stress was unbalanced in mice with decreased eIF2α phosphorylation preceding inflammation. In IL10/Nox1dKO mice, salubrinal preserved eIF2α phosphorylation through inhibition of the regulatory subunit of the protein phosphatase 1 PP1R15A/GADD34 and prevented colitis. Thus, this new experimental model highlighted the central role of epithelial ER stress abnormalities in the development of colitis and defined the defective eIF2α pathway as a key pathophysiological target for UC. Therefore, specific regulators able to restore the defective eIF2α pathway could lead to the molecular remission needed to treat UC.

  8. Approaches to the evaluation of chemical-induced immunotoxicity.

    OpenAIRE

    Krzystyniak, K; Tryphonas, H; Fournier, M

    1995-01-01

    The immune system plays a crucial role in maintaining health; however, accumulating evidence indicates that this system can be the target for immunotoxic effects caused by a variety of chemicals including the environmental pollutants of polychlorinated biphenyls, chlorinated dibenzo-p-dioxins, pesticides, and heavy metals. Adverse chemical-induced immunomodulation, which is studied within the discipline of immunotoxicology, may be expressed either as immunosuppression/immunodepression or immu...

  9. Neuro-immune interactions in chemical-induced airway hyperreactivity.

    Science.gov (United States)

    Devos, Fien C; Boonen, Brett; Alpizar, Yeranddy A; Maes, Tania; Hox, Valérie; Seys, Sven; Pollaris, Lore; Liston, Adrian; Nemery, Benoit; Talavera, Karel; Hoet, Peter H M; Vanoirbeek, Jeroen A J

    2016-08-01

    Asthma may be induced by chemical sensitisers, via mechanisms that are still poorly understood. This type of asthma is characterised by airway hyperreactivity (AHR) and little airway inflammation. Since potent chemical sensitisers, such as toluene-2,4-diisocyanate (TDI), are also sensory irritants, it is suggested that chemical-induced asthma relies on neuro-immune mechanisms.We investigated the involvement of transient receptor potential channels (TRP) A1 and V1, major chemosensors in the airways, and mast cells, known for their ability to communicate with sensory nerves, in chemical-induced AHR.In vitro intracellular calcium imaging and patch-clamp recordings in TRPA1- and TRPV1-expressing Chinese hamster ovarian cells showed that TDI activates murine TRPA1, but not TRPV1. Using an in vivo model, in which an airway challenge with TDI induces AHR in TDI-sensitised C57Bl/6 mice, we demonstrated that AHR does not develop, despite successful sensitisation, in Trpa1 and Trpv1 knockout mice, and wild-type mice pretreated with a TRPA1 blocker or a substance P receptor antagonist. TDI-induced AHR was also abolished in mast cell deficient Kit(Wsh) (/Wsh) mice, and in wild-type mice pretreated with the mast cell stabiliser ketotifen, without changes in immunological parameters.These data demonstrate that TRPA1, TRPV1 and mast cells play an indispensable role in the development of TDI-elicited AHR. PMID:27126687

  10. Chemical changes induced by ultrasound in iron

    Science.gov (United States)

    Albertini, G.; Calbucci, V.; Cardone, F.; Petrucci, A.; Ridolfi, F.

    2014-03-01

    The focus of this work is a careful chemical investigation of structural damage produced by the exposure of an iron bar to pressure waves generated using an ultrasound machine (called the R-1-S reactor). In addition to the emission of neutron bursts, the ultrasound treatment caused the appearance of zones of macroscopic damage (˜1 mm in size) on the exterior of the bar. Reflected-light optical and environmental scanning electron microscopy (ESEM) has shown that these external damage zones are characterized by microcraters and are covered by a thin layer of cracked amorphous material. Under back scattered electron (BSE) observation, this material shows a lower brightness than the intact ferrite surface. In addition, a zone with a high density of deformed cavities (˜1300 per mm2) with irregular walls and a maximum size of 10 μm was found inside the bar. These deformed microcavities are partially filled with a material composed of a chaotic assemblage of submicron-sized (most likely amorphous) particles. A careful compositional investigation of the chaotic material inside the microcavities using the semi-quantitative data obtained with the ESEM X-ray Energy Dispersive System (EDS) has shown that it is primarily composed of carbon, manganese and chromium. These elements are also found in lower amounts within the intact ferrite matrix. In contrast, the damaged surface surrounding the craters is characterized by elements not found in the ferrite at all (i.e., O, Cl, K, Cu); elements the presence of which cannot be attributed to the occurrence of non-metallic inclusions or to contamination during fabrication. These results are also difficult to explain using the generally accepted laws of physics; however, they do appear to agree with a recent theory predicting the deformation of the local spacetime and the violation of the Local Lorentz Invariance. Such a violation should occur following the collapse of micron-sized discontinuities internal to the materials

  11. AOM/DSS Model of Colitis-Associated Cancer.

    Science.gov (United States)

    Parang, Bobak; Barrett, Caitlyn W; Williams, Christopher S

    2016-01-01

    Our understanding of colitis-associated carcinoma (CAC) has benefited substantially from mouse models that faithfully recapitulate human CAC. Chemical models, in particular, have enabled fast and efficient analysis of genetic and environmental modulators of CAC without the added requirement of time-intensive genetic crossings. Here we describe the Azoxymethane (AOM)/Dextran Sodium Sulfate (DSS) mouse model of inflammatory colorectal cancer.

  12. MD-1 deficiency attenuates dextran sodium sulfate (DSS)-induced colitis through modulating the function of colonic lamina propria dendritic cells.

    Science.gov (United States)

    Pan, Huaqin; Zhang, Guqin; Zhang, Lin; Wang, Wei; Shang, Jian; Wang, Xiaobing; Zhao, Qiu; Li, Jin

    2016-07-01

    Available evidence suggests that both dysregulated innate and adaptive immune pathways contribute to the aberrant intestinal inflammatory response in patients with inflammatory bowel disease (IBD). Myeloid Differentiation 1 (MD-1), also known as Lymphocyte Antigen 86 (Ly86), a secreted protein interacting with radioprotective 105 (RP105), plays an important role in Toll-like receptor 4 (TLR4) signaling pathway. Previous studies showed that MD-1 may be involved in the (patho) physiological regulation of the innate immune system and inflammation. In this study, we reported for the first time that MD-1 mRNA expression was up-regulated in both human IBD patients and DSS-treated WT mice. We showed that MD-1(-/-) mice were less susceptible to the development of colitis than WT controls as demonstrated by significantly reduced weight loss, disease activity index, colon histological scores, cellular infiltration and expression of inflammatory mediators. In addition, mucosal barrier function seemed to be intact in response to the loss of MD-1. Finally, lamina propria dendritic cells (LPDCs) from the colon of MD-1(-/-) mice after DSS exposure not only decreased in number but also significantly down-regulated the expression of surface maturation co-stimulatory molecules MHC-II, CD40 and CD86 compared with those from WT mice. Taken together, our results reveal that MD-1 deficiency is of critical importance in down-regulating induction and progression of DSS colitis, thereby suggesting that MD-1 might be a target for future interventional therapies of IBD.

  13. CXC chemokine receptor 3 expression increases the disease-inducing potential of CD4+ CD25- T cells in adoptive transfer colitis

    DEFF Research Database (Denmark)

    Kristensen, Nanna Ny; Gad, Monika; Thomsen, Allan Randrup;

    2006-01-01

    of enteroantigen specificity; we also tested the enteroantigen-specific proliferative ability of CD4CD25 T cells from CXCR3 mice in vitro and found that they respond even more strongly than wild-type cells. CONCLUSIONS: The present data indicate that CXCR3 plays an important role in controlling the migration......-inflammatory therapy in inflammatory bowel disease. In this study, we have investigated the role of the chemokine receptor CXCR3 in the development of chronic colitis in a murine model. METHOD: Expression of CXCR3 on CD4 T cell from normal and colitic mice was assessed by flow cytometry. Development of colitis...... was followed after transfer of either normal or CXCR3CD4CD25T cell into immunodeficient host. In addition, the ability of regulatory T cell to function in vivo in the absence of CXCR3 was tested. RESULTS: We find CXCR3 to be expressed on 80% to 90% of CD4 T cells isolated from colitic mice compared with only 4...

  14. DNA and RNA induced enantioselectivity in chemical synthesis

    NARCIS (Netherlands)

    Roelfes, Gerard

    2007-01-01

    One of the hallmarks of DNA and RNA structures is their elegant chirality. Using these chiral structures to induce enantioselectivity in chemical synthesis is as enticing as it is challenging. In recent years, three general approaches have been developed to achieve this, including chirality transfer

  15. A model for chemically-induced mechanical loading on MEMS

    DEFF Research Database (Denmark)

    Amiot, Fabien

    2007-01-01

    The development of full displacement field measurements as an alternative to the optical lever technique to measure the mechanical response for microelectro-mechanical systems components in their environment calls for a modeling of chemically-induced mechanical fields (stress, strain, and displac...

  16. Anti-inflammatory efficiency of levobupivacaine in an experimental colitis model

    Institute of Scientific and Technical Information of China (English)

    Ugur; Duman; Aysun; Yilmazlar; Ersin; Ozturk; Sibel; Aker

    2010-01-01

    AIM:To investigate the efficiency of levobupivacaine in treating experimentally induced colitis in rats.METHODS:Colitis was induced by trinitrobenzene sulfonic acid and ethanol in 30 rats under general anesthesia,and 10 rats were used as a sham group.Subsequent to induction of colitis,rats were divided into three groups;budesonide group received 0.1 mg/kg budesonide,levobupivacaine group received 10 mg/kg levobupivacaine and saline group received 1 mL saline solution via rectal route for 7 d.In the sham gro...

  17. Mesalamine treatment mimicking relapse in a child with ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Iva Hojsak; Ana M Pavić; Sanja Kolaček

    2014-01-01

    Background: There are reports on mesalamine-induced bloody diarrhea mimicking ulcerative colitis (UC) relapse, mostly in adults. Methods: Herein we present a case of a child with UC who developed relapse of hemorrhagic colitis related to mesalamine. Results: A 10-year-old girl developed severe symptoms mimicking UC relapse 3 weeks after introduction of mesalamine therapy. After mesalamine was withdrawn, her symptoms improved, but deteriorated again during the challenge of mesalamine despite concomitant use of corticosteroids. Conclusion: This is the fi rst case report on such a young child during the concomitant use of corticosteroids.

  18. Management of pediatric ulcerative colitis

    DEFF Research Database (Denmark)

    Turner, Dan; Levine, Arie; Escher, Johanna C;

    2012-01-01

    Pediatric ulcerative colitis (UC) shares many features with adult-onset disease but there are some unique considerations; therefore, therapeutic approaches have to be adapted to these particular needs. We aimed to formulate guidelines for managing UC in children based on a systematic review (SR......) of the literature and a robust consensus process. The present article is a product of a joint effort of the European Crohn's and Colitis Organization (ECCO) and the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN)....

  19. Treatment with diammonium glycyrrhizinate down-regulates M30 expression in ulcerative colitis in rats

    Institute of Scientific and Technical Information of China (English)

    原皓

    2013-01-01

    Objective To assess the therapeutic effect of diammonium glycyrrhizinate(DG) on2,4,6-trinitro-benzene sulfonic acid(TNBS)-induced ulcerative colitis in rats and to explore the underlying mechanisms by

  20. [Ischemic colitis after renal transplantation:etiology and pathogenesis].

    Science.gov (United States)

    Alperovich, G; Idiarte, L; Besasso, O; Avagnina, A

    2003-01-01

    Ischemic colitis is a well-recognized complication occurring in renal transplant recipients. It has often been associated with cytomegalovirus (CMV) vasculitis. However, the diagnosis of this pathology in the absence of CMV suggests that other etiological factors might be involved. Drugs inducing mesenteric vasoconstriction, such as non-steroidal anti-inflamatory drugs (NSAIDs) and cyclosporine could be related to this entity.

  1. R-Spondins Are Expressed by the Intestinal Stroma and are Differentially Regulated during Citrobacter rodentium- and DSS-Induced Colitis in Mice.

    Science.gov (United States)

    Kang, Eugene; Yousefi, Mitra; Gruenheid, Samantha

    2016-01-01

    The R-spondin family of proteins has recently been described as secreted enhancers of β-catenin activation through the canonical Wnt signaling pathway. We previously reported that Rspo2 is a major determinant of susceptibility to Citrobacter rodentium-mediated colitis in mice and recent genome-wide association studies have revealed RSPO3 as a candidate Crohn's disease-specific inflammatory bowel disease susceptibility gene in humans. However, there is little information on the endogenous expression and cellular source of R-spondins in the colon at steady state and during intestinal inflammation. RNA sequencing and qRT-PCR were used to assess the expression of R-spondins at steady state and in two mouse models of colonic inflammation. The cellular source of R-spondins was assessed in specific colonic cell populations isolated by cell sorting. Data mining from publicly available datasets was used to assess the expression of R-spondins in the human colon. At steady state, colonic expression of R-spondins was found to be exclusive to non-epithelial CD45- lamina propria cells, and Rspo3/RSPO3 was the most highly expressed R-spondin in both mouse and human colon. R-spondin expression was found to be highly dynamic and differentially regulated during C. rodentium infection and dextran sodium sulfate (DSS) colitis, with notably high levels of Rspo3 expression during DSS colitis, and high levels of Rspo2 expression during C. rodentium infection, specifically in susceptible mice. Our data are consistent with the hypothesis that in the colon, R-spondins are expressed by subepithelial stromal cells, and that Rspo3/RSPO3 is the family member most implicated in colonic homeostasis. The differential regulation of the R-spondins in different models of intestinal inflammation indicate they respond to specific pathogenic and inflammatory signals that differ in the two models and provides further evidence that this family of proteins plays a key role in linking intestinal

  2. Luminal and parenteral TFF2 and TFF3 dimer and monomer in two models of experimental colitis in the rat

    DEFF Research Database (Denmark)

    Poulsen, Steen Seier; Kissow, Hannelouise; Hare, Kristine;

    2005-01-01

    % dextran sodium sulphate in the drinking water or by one intraperitoneal injection of mitomycin C, 3.75 mg/kg. TFF peptides were administered as subcutaneous injections or directly into the lumen via a catheter placed in the proximal colon. Treatments were saline, TFF2, TFF3 monomer or TFF3 dimer 5 mg....../kg twice per day throughout the study [dextran sulphate sodium (DSS)] or from day 4 to 7 (mitomycin C). Colitis severity was scored in a stereomicroscope and histologically. RESULTS: Luminal treatment with TFF3 in its dimeric form significantly improved the colitis score in both colitis models, whereas TFF...... in both colitis models. CONCLUSIONS: Intracolonic administration of TFF3 dimer and TFF2 improves experimentally induced colitis in rats. The TFF3 monomer has no effect. Parenteral administration of TFF peptides aggravates the colitis especially the TFF3 monomer....

  3. Lactobacillus bulgaricus OLL1181 activates the aryl hydrocarbon receptor pathway and inhibits colitis.

    Science.gov (United States)

    Takamura, Takeyuki; Harama, Daisuke; Fukumoto, Suguru; Nakamura, Yuki; Shimokawa, Naomi; Ishimaru, Kayoko; Ikegami, Shuji; Makino, Seiya; Kitamura, Masanori; Nakao, Atsuhito

    2011-10-01

    Increasing evidence suggests that the aryl hydrocarbon receptor (AhR) pathway has an important role in the regulation of inflammatory responses. Most recently, we have shown that the activation of the AhR pathway by a potent AhR agonist inhibits the development of dextran sodium sulfate (DSS)-induced colitis, a model of human ulcerative colitis, by the induction of prostaglandin E2 (PGE2) in the large intestine. Because several strains of probiotic lactic acid bacteria have been reported to inhibit DSS-induced colitis by unidentified mechanisms, we hypothesized that particular strains of lactic acid bacterium might have the potential to activate the AhR pathway, thereby inhibiting DSS-induced colitis. This study investigated whether there are specific lactic acid bacterial strains that can activate the AhR pathway, and if so, whether this AhR-activating potential is associated with suppression of DSS-induced colitis. By using AhR signaling reporter cells, we found that Lactobacillus bulgaricus OLL1181 had the potential to activate the AhR pathway. OLL1181 also induced the mRNA expression of cytochrome P450 family 1A1 (CYP1A1), a target gene of the AhR pathway, in human colon cells, which was inhibited by the addition of an AhR antagonist, α-naphthoflavon (αNF). In addition, mice treated orally with OLL1181 showed an increase in CYP1A1 mRNA expression in the large intestine and amelioration of DSS-induced colitis. Thus, OLL1181 can induce activation of the intestinal AhR pathway and inhibit DSS-induced colitis in mice. This strain of lactic acid bacterium has therefore the potential to activate the AhR pathway, which may be able to suppress colitis.

  4. Intestine-Specific Mttp Deletion Increases the Severity of Experimental Colitis and Leads to Greater Tumor Burden in a Model of Colitis Associated Cancer

    OpenAIRE

    Yan Xie; Hitoshi Matsumoto; Ilke Nalbantoglu; Kerr, Thomas A.; Jianyang Luo; Rubin, Deborah C; Susan Kennedy; Davidson, Nicholas O.

    2013-01-01

    Background Gut derived lipid factors have been implicated in systemic injury and inflammation but the precise pathways involved are unknown. In addition, dietary fat intake and obesity are independent risk factors for the development of colorectal cancer. Here we studied the severity of experimental colitis and the development of colitis associated cancer (CAC) in mice with an inducible block in chylomicron secretion and fat malabsorption, following intestine-specific deletion of microsomal t...

  5. Protective effect of silymarin against chemical-induced cardiotoxicity

    Directory of Open Access Journals (Sweden)

    Bibi Marjan Razavi

    2016-09-01

    Full Text Available Cardiac disorders remain one of the most important causes of death in the world. Oxidative stress has been suggested as one of the molecular mechanisms involved in drug-induced cardiac toxicity. Recently, several natural products have been utilized in different studies with the aim to protect the progression of oxidative stress-induced cardiac disorders. There is a large body of evidence that administration of antioxidants may be useful in ameliorating cardiac toxicity. Silymarin, a polyphenolic flavonoid has been shown to have utility in several cardiovascular disorders. In this review, various studies in scientific databases regarding the preventive effects of silymarin against cardiotoxicity induced by chemicals were introduced. Although there are many studies representing the valuable effects of silymarin in different diseases, the number of researches relating to the possible cardiac protective effects of silymarin against drugs induced toxicity is rather limited. Results of these studies show that silymarin has a broad spectrum of cardiac protective activity against toxicity induced by some chemicals including metals, environmental pollutants, oxidative agents and anticancer drugs. Further studies are needed to establish the utility of silymarin in protection against cardiac toxicity.

  6. Keratin expression in chemically induced mouse lung adenomas.

    OpenAIRE

    Gunning, W T; Goldblatt, P. J.; Stoner, G D

    1992-01-01

    Chemically induced mouse lung tumors exhibit distinctive growth patterns, characterized by an alveolar or solid appearance, a papillary appearance, or a combination of the two. Lung tumors induced in strain A/J mice by either benzo(a)pyrene (BP) or by N-nitrosoethylurea (ENU) were examined for expression of low- and high-molecular-weight cytokeratins. Simple cytokeratins (low molecular weight) were found in all epithelial cells of the normal mouse lung and in all tumor types, whereas higher-m...

  7. Atypical disease phenotypes in pediatric ulcerative colitis

    DEFF Research Database (Denmark)

    Levine, Arie; de Bie, Charlotte I; Turner, Dan;

    2013-01-01

    Definitive diagnosis of pediatric ulcerative colitis (UC) may be particularly challenging since isolated colitis with overlapping features is common in pediatric Crohn's disease (CD), while atypical phenotypes of UC are not uncommon. The Paris classification allows more accurate phenotyping...

  8. Heligmosomoides polygyrus bakeri infection activates colonic FoxP3+ T cells enhancing their capacity to prevent colitis

    Science.gov (United States)

    Helminthic infections protect mice from colitis in murine models of inflammatory bowel disease and also may protect people. Helminths like Heligmosomoides bakeri (Hpb) can induce Tregs. Experiments explored if Hpb infection could protect mice from colitis through activation of colonic Treg and exam...

  9. Chemically induced electric field: flat band potential engineering

    Science.gov (United States)

    Bak, T.; Guo, Z.; Li, W.; Atanacio, A. J.; Nowotny, J.

    2012-10-01

    The present work considers engineering of the flat band potential, FBP, of metal oxides in a controlled manner. The aim is to minimise the energy losses related to recombination. The related experimental approaches include imposition of a chemically-induced electric field using the phenomena of segregation, diffusion and the formation of multilayer systems. This paper considers several basic phenomena that allow the modification of the surface charge and the space charge at the gas/solid and solid/liquid interfaces.

  10. Laser-Induced Chemical Vapour Deposition of Silicon Carbonitride

    OpenAIRE

    Besling, W.; van der Put, P.; Schoonman, J.

    1995-01-01

    Laser-induced Chemical Vapour Deposition of silicon carbonitride coatings and powders has been investigated using hexamethyldisilazane (HMDS) and ammonia as reactants. An industrial CW CO2-laser in parallel configuration has been used to heat up the reactant gases. HMDS dissociates in the laser beam and reactive radicals are formed which increase rapidly in molecular weight by an addition mechanism. Dense polymer-like silicon carbonitride thin films and nanosized powders are formed depending ...

  11. Investigation of pulmonary involvement in inflammatory bowel disease in an experimental model of colitis

    Science.gov (United States)

    Aydin, Bunyamin; Songur, Yıldıran; Songur, Necla; Aksu, Oğuzhan; Senol, Altug; Ciris, I. Metin; Sutcu, Recep

    2016-01-01

    Background/Aims: Inflammatory bowel disease (IBD) may also involve various extra-intestinal organs. Clinical studies have found asymptomatic/symptomatic pulmonary involvement in 1% to 6% of patients with IBD. The present study histopathologically investigated pulmonary involvement in an experimental model of colitis in order to demonstrate pulmonary tissue involvement in IBD and to expose potential etiological factors. It also explored the relation between inflammation and tissue concentrations of vascular endothelial growth factor (VEGF) and tumor necrosis factor α (TNF-α). Methods: The study comprised 24 male Wistar albino rats. The rats were divided into four groups of six rats each. Acute colitis was induced in two separate groups using either the dextran sulphate sodium (DSS) or trinitrobenzene sulfonic acid (TNBS) method, while the other two groups were used as controls for each model of colitis. Wallace scoring was used for macroscopic assessment of colitis, and the lungs were histopathologically examined. Concentrations of VEGF and TNF-α in pulmonary tissue were measured by the enzyme-linked immunosorbent assay method. Results: The number of animals that had alveolar hemorrhage was significantly higher in the TNBS-induced colitis and DSS-induced colitis groups compared to their own control groups (p = 0.015 and p = 0.015, respectively). VEGF and TNF-α concentrations in pulmonary tissues were significantly increased in both the TNBS colitis and DSS colitis groups compared to their own control groups (p = 0.002 and p = 0.004, respectively; and p = 0.002 and p = 0.002, respectively). Conclusions: The present study demonstrated that significant and serious histopathological changes directly associated with colitis occur in the lungs in IBD. PMID:27539446

  12. Activation of aryl hydrocarbon receptor (AhR leads to reciprocal epigenetic regulation of FoxP3 and IL-17 expression and amelioration of experimental colitis.

    Directory of Open Access Journals (Sweden)

    Narendra P Singh

    Full Text Available BACKGROUND: Aryl hydrocarbon receptor (AhR, a transcription factor of the bHLH/PAS family, is well characterized to regulate the biochemical and toxic effects of environmental chemicals. More recently, AhR activation has been shown to regulate the differentiation of Foxp3(+ Tregs as well as Th17 cells. However, the precise mechanisms are unclear. In the current study, we investigated the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, a potent AhR ligand, on epigenetic regulation leading to altered Treg/Th17 differentiation, and consequent suppression of colitis. METHODOLOGY/PRINCIPAL FINDINGS: Dextran sodium sulphate (DSS administration induced acute colitis in C57BL/6 mice, as shown by significant weight loss, shortening of colon, mucosal ulceration, and increased presence of CXCR3(+ T cells as well as inflammatory cytokines. Interestingly, a single dose of TCDD (25 µg/kg body weight was able to attenuate all of the clinical and inflammatory markers of colitis. Analysis of T cells in the lamina propria (LP and mesenteric lymph nodes (MLN, during colitis, revealed decreased presence of Tregs and increased induction of Th17 cells, which was reversed following TCDD treatment. Activation of T cells from AhR(+/+ but not AhR (-/- mice, in the presence of TCDD, promoted increased differentiation of Tregs while inhibiting Th17 cells. Analysis of MLN or LP cells during colitis revealed increased methylation of CpG islands of Foxp3 and demethylation of IL-17 promoters, which was reversed following TCDD treatment. CONCLUSIONS/SIGNIFICANCE: These studies demonstrate for the first time that AhR activation promotes epigenetic regulation thereby influencing reciprocal differentiation of Tregs and Th17 cells, and amelioration of inflammation.

  13. Intracolonic Vancomycin for Severe Clostridium difficile Colitis

    OpenAIRE

    Kim, Peter K.; Huh, Heesun C.; Cohen, Hillel W.; Feinberg, Elyssa J.; Ahmad, Salman; Coyle, Christina; Teperman, Sheldon; Boothe, Hugh

    2013-01-01

    Background: Clostridium difficile colitis is associated with increased age, antibiotic usage, and hospitalization. Severe C. difficile colitis refractory to medical therapy may require surgical intervention including subtotal colectomy. We initiated an adjuvant intracolonic vancomycin (ICV) enema protocol for inpatients with severe C. difficile colitis and compared the response to this therapy in patients from the community and nursing homes.

  14. Matrine ameliorates spontaneously developed colitis in interleukin-10-deficient mice.

    Science.gov (United States)

    Wu, Cong; Xu, Zheng; Gai, Renhua; Huang, Kehe

    2016-07-01

    Interleukin-10 (IL-10)-deficient mice spontaneously develop T cell-mediated colitis. Previous reports have shown that Matrine may reduce the symptoms of acute colitis induced by trinitrobenzene sulfonic acid (TNBS). However, whether Matrine impacts chronic colitis remains unknown. In this study, we investigated whether Matrine could limit the symptoms of spontaneously developed colitis and its potential molecular mechanisms. IL-10 deficient mice were given Matrine or a PBS control by oral gavage daily for 4weeks and were euthanized at week 2 or week 4. We measured body weight, colon length and weight, and histological scores. We also evaluated the spontaneous secretion of IL-12/23p40, IFN-γ and IL-17 in colon explant cultures as well as IFN-γ and IL-17 secretion in unseparated mesenteric lymph node (MLN) cells, and assessed IFN-γ, IL-17, IL-1β and IL-6 mRNA expression in colon tissue. In addition, we analyzed the proportions of CD4-positive and CD8-positive cells in unseparated MLN cells. Our results show that Matrine-treated mice exhibited better body weight recovery than controls and that histological scores and spontaneously secreted IL-12/23p40, IFN-γ and IL-17 in colon tissue were significantly decreased in treated mice compared with controls. The proportion of CD4-positive cells of MLNs in treated mice was significantly smaller than that in controls at week 4. Both cytokine production and mRNA expression of IFN-γ and IL-17 were significantly reduced in treated mice compared with controls. Taken together, our results indicate that Matrine may ameliorate spontaneously developed chronic colitis and could be considered as a therapeutic alternative for chronic colitis.

  15. CT evaluation of infectious colitis

    International Nuclear Information System (INIS)

    Computed tomography (CT) is useful for evaluating the diagnosis of gastrointestinal disease, such as infectious colitis, in patients with severe pain and bloody diarrhea. During the 7 years between November 1993 and October 2000, 34 patients with infectious colitis (18 male, 16 female; mean age 42±19 yrs), received emergency CT and colonoscopy because of severe abdominal pain and dysentery. The following organisms were isolated: pathogenic Escherichia coli (12), 6 of which were O157: H7 (O-157), Salmonella species (11), Campylobacter species (5), Vibrio parahaemolyticus (3), Yersinia enterocolotica (2) and Shigella species (1). Thickening of the intestinal wall greater than 10 mm was seen in the ascending colon in the 6 cases with E. coli O157, in 5/11 cases with Salmonella, 4/5 with Campylobacter and 1/6 with non-O157 pathogenic E. Coli. marked intestinal wall thickening, greater than 20 mm, was seen in the ascending colon of the 4 of the patients with an O-157 infection. In all patients with O-157 colitis, slight ascites was noted in the pelvic space. In additions, ascites was also seen in 3/13 patients with Salmonella and 1/5 patients with Campylobacter colitis. The CT findings, in the patients with infectious colitis, are non-specific but knowledge and recognition of the findings will help in patient evaluation and proper treatment. (author)

  16. Substance P modulates colitis-associated fibrosis.

    Science.gov (United States)

    Koon, Hon Wai; Shih, David; Karagiannides, Iordanes; Zhao, Dezheng; Fazelbhoy, Zafeer; Hing, Tressia; Xu, Hua; Lu, Bao; Gerard, Norma; Pothoulakis, Charalabos

    2010-11-01

    Substance P (SP) and the neurokinin-1 receptor (NK-1R) are involved in the development of colitis and mucosal healing after colonic inflammation. We studied whether SP modulates colonic fibrosis by using a chronic model of trinitrobenzenesulfonic acid (TNBS)-induced colitis in wild-type (WT) and NK-1R-deficient (NK-1R KD) mice. We found increased mRNA expression levels of collagen, vimentin, and the fibrogenic factors transforming growth factor β1 and insulin-like growth factor 1 in the chronically inflamed colons of WT mice treated with repeated intracolonic TNBS administrations. Fibrosis in TNBS-treated mice was also evident immunohistochemically by collagen deposition in the colon. Treatment of TNBS-exposed WT mice with the NK-1R antagonist CJ-12255 reduced colonic inflammation, colonic fibrosis, fibroblast accumulation, and expression levels of the fibrogenic factors. NK-1R knockout mice chronically exposed to TNBS had similar colonic inflammation compared with WT, but reduced colonic fibrosis, fibroblast accumulation, and expression levels of fibrogenic factors. Immunohistochemical staining also showed co-localization of NK-1R with fibroblasts in inflamed colons of mice and in colonic mucosa of patients with Crohn's disease. Exposure of human colonic CCD-18Co fibroblasts to SP (10 nmol/L) increased cell migration. SP stimulated collagen synthesis in CCD-18Co fibroblasts in the presence of transforming growth factor β1 and insulin-like growth factor 1, and this effect was reduced by Akt inhibition. Thus, SP, via NK-1R, promotes intestinal fibrogenesis after chronic colitis by stimulating fibrotic responses in fibroblasts. PMID:20889569

  17. Therapeutical effect of Allicin for colitis mice induced by DSS and its possible mechanisms%Allicin对DSS诱导的小鼠结肠炎的治疗作用及可能机制

    Institute of Scientific and Technical Information of China (English)

    陈晶; 李巧霞; 李玮; 李宏; 汤菲; 王缚鲲

    2016-01-01

    Objective:To analyze the therapeutical effect of Allicin for colitis mice induced by DSS and its possible mechanisms. Methods:A total of 24 male mice were randomly divided into Control group,DSS group(2. 5% DSS,7 days) and Allicin group [DSS treatment and Allicin,10 mg/(kg·d),7 d]. Disease activity index,inflammatory score,TUNEL and Western bolt were performed to analyze the effect of Allicin on colitis induced by DSS. Results: With DSS group, the Allicin group had lower disease activity score and inflammatory score(P<0. 05). Allicin group had a lower number of intestinal epithelial cell apoptosis than that of DSS group,the difference was statistically significant(P<0. 05). Western bolt analysis shown that Allicin treatment significantly depressed the expression of p-JAK2 and p-STAT3 in intestinal mucosa when compared with these of DSS group ( P<0. 05 ) . Conclusion:Conclusion Allicin has significantly therapeutic effect on mice colitis induced by DSS, the possible mechanisms including anti-inflammatory effects,protected of the intestinal epithelial cells and inhibition of the JAK2/STAT3 signaling pathways.%目的::明确Allicin对DSS诱导的小鼠结肠炎的治疗作用并进一步分析可能的机制。方法:将24只8周龄雄性BALB/c小鼠随机分为3组:Control组:阴性对照;DSS组:2.5%DSS诱导结肠炎;Allicin组:2.5%DSS诱导结肠炎+Allicin治疗[10 mg/(kg·d),共7 d]。结果:与DSS组比较,Allicin组疾病活动度评分及肠道炎症评分显著降低(P<0.05)。 Allicin治疗组小鼠肠上皮细胞凋亡数目显著低于DSS组。 Allicin治疗组小鼠肠黏膜炎症因子( IL-6、IL-1β及TNF-α)水平显著低于DSS组,差异均具有统计学意义( P<0.05)。与DSS组比较, Allicin治疗显著抑制了肠黏膜p-JAK2及p-STAT3的表达( P<0.05)。结论:Allicin对DSS小鼠肠炎具有治疗作用,可能的机制包括抗炎,保护肠上皮细胞及抑制JAK2/STAT3信号通路等。

  18. Brachyspira murdochii colitis in pigs

    DEFF Research Database (Denmark)

    Jensen, Tim Kåre; Christensen, A. S.; Boye, Mette

    2010-01-01

    The weakly beta-hemolytic porcine spirochete Brachyspira murdochii is considered a normal intestinal commensal. In the present study, however, a field case of B murdochii–associated catarrhal colitis was identified in a pig, as characterized by extensive spirochetal colonization of the surface...... epithelium. Experimentally, 8 weaned pigs were challenged with the B murdochii isolate, reproducing catarrhal colitis in 2 animals. By applying fluorescent in situ hybridization using a species-specific oligonucleotide probe targeting 23S rRNA, B murdochii organisms were found in high numbers and were...... closely associated with the surface epithelium in the pigs with catarrhal colitis. The results indicate that, when present in high numbers, B murdochii is low pathogenic for pigs....

  19. Effect of folate deficiency on experimental colitis in mice induced by dextran sodium sulfate%叶酸缺乏对葡聚糖硫酸钠诱导的小鼠实验性结肠炎的影响

    Institute of Scientific and Technical Information of China (English)

    马玉萍; 肖锐; 方维丽; 李海东; 刘文天

    2015-01-01

    Objective To investigate whether folate deficiency cause high expression level of interferon gamma (IFN-γ) resulted from IFN-γ gene ( IFNG) hypomethylation and then promote the pathogenesis and development of ulcerative colitis (UC ) in a dextran sulfate sodium (DSS )-induced experimental colitis model in mice .Methods A total of 24 female BALB/c mice were divided into four groups ,six mice in each group , including folate deficient/DSS+ group , standard diet/DSS+ group , standard diet/DSS - group and folate deficient/DSS- group .At the beginning of the sixth week since fed , the mice of model groups were treated with 5% DSS to establish experimental colitis .By the end of the sixth week ,disease activity index (DAI) of colitis and histological changes were evaluated .The folate level of peripheral blood serum of mice were detected by enzyme-linked immunosorbent assay (ELISA ) . The expression of IFN-γ in colonic mucosa of mice was examined by immunohistochemistry . The methylation level of CpG island in the promoter region of IFNG was determined by methylation specific polymerase chain reaction (MSP) .The t test was used for measurement data .Chi square test was performed for comparison between groups of count data . Spearman correlation analysis was used for correlation analysis .Results The folate levels of peripheral blood serum of folate deficiency/DSS+ group and folate deficiency/DSS- group ((2 .70 ± 0 .19) and (2 .80 ± 0 .25)μg/L) were significantly lower than those of standard diet/DSS+ group and standard diet/DSS- group ((13 .62 ± 0 .38 ) and (13 .52 ± 0 .77)μg/L ,t= -63 .33、32 .27 ,both P< 0 .05) ,resepectively .The expression of IFN-γ in colonic mucosa of folate deficiency/DSS+ group and standard diet/DSS+ group were significantly higher than those of folate deficiency/DSS- group and standard diet/DSS- group (χ2 = 22 .18 ,P< 0 .05 ) . And the expression of IFN-γ in colonic mucosa of folate deficiency/DSS+ group was also higher than that of

  20. NKT cells mediate the recruitment of neutrophils by stimulating epithelial chemokine secretion during colitis.

    Science.gov (United States)

    Huang, Enyu; Liu, Ronghua; Lu, Zhou; Liu, Jiajing; Liu, Xiaoming; Zhang, Dan; Chu, Yiwei

    2016-05-27

    Ulcerative colitis (UC) is a kind of inflammatory bowel diseases characterized by chronic inflammation and ulcer in colon, and UC patients have increased risk of getting colorectal cancer. NKT cells are cells that express both NK cell markers and semi-invariant CD1d-restricted TCRs, can regulate immune responses via secreting a variety of cytokines upon activation. In our research, we found that the NKT cell-deficient CD1d(-/-) mice had relieved colitis in the DSS-induced colitis model. Further investigations revealed that the colon of CD1d(-/-) mice expressed less neutrophil-attracting chemokine CXCL 1, 2 and 3, and had decreased neutrophil infiltration. Infiltrated neutrophils also produced less reactive oxygen species (ROS) and TNF-α, indicating they may cause less epithelial damage. In addition, colitis-associated colorectal cancer was also relieved in CD1d(-/-) mice. During colitis, NKT cells strongly expressed TNF-α, which could stimulate CXCL 1, 2, 3 expressions by the epithelium. In conclusion, NKT cells can regulate colitis via the NKT cell-epithelium-neutrophil axis. Targeting this mechanism may help to improve the therapy of UC and prevent colitis-associated colorectal cancer. PMID:27063801

  1. Sequential release of cytokines, lipid mediators and nitric oxide in experimental colitis

    OpenAIRE

    Dijk, A. P. M. van; Keuskamp, Z. J.; Wilson, J. H. P.; Zijlstra, F. J.

    1995-01-01

    textabstractThe object of this study was to establish whether different pro- and anti-inflammatory mediators were formed in colonic tissue from experimental colitis depending on the course of the disease. Concentrations of mediators of inflammation were examined in colonic tissue in dextran induced colitis in mice. Initial inflammation was produced by 5 days treatment of 10% dextran sodium sulfate (DSS) in drinking water, followed by a further 9 day period of 2% DSS in an attempt to produce a...

  2. Schistosoma mansoni proteins attenuate gastrointestinal motility disturbances during experimental colitis in mice

    Institute of Scientific and Technical Information of China (English)

    Nathalie; E; Ruyssers; Benedicte; Y; De; Winter; Joris; G; De; Man; Natacha; D; Ruyssers; Ann; J; Van; Gils; Alex; Loukas; Mark; S; Pearson; Joel; V; Weinstock; Paul; A; Pelckmans; Tom; G; Moreels

    2010-01-01

    AIM:To investigate the therapeutic effect of Schistosoma mansoni(S.mansoni) soluble worm proteins on gastrointestinal motility disturbances during experimental colitis in mice. METHODS:Colitis was induced by intrarectal injection of trinitrobenzene sulphate(TNBS) and 6 h later,mice were treated ip with S.mansoni proteins.Experiments were performed 5 d after TNBS injection.Inflammationwas quantified using validated inflammation parameters. Gastric emptying and geometric center were measured to assess in vivo...

  3. Pglyrp-Regulated Gut Microflora Prevotella falsenii, Parabacteroides distasonis and Bacteroides eggerthii Enhance and Alistipes finegoldii Attenuates Colitis in Mice.

    Science.gov (United States)

    Dziarski, Roman; Park, Shin Yong; Kashyap, Des Raj; Dowd, Scot E; Gupta, Dipika

    2016-01-01

    Dysbiosis is a hallmark of inflammatory bowel disease (IBD), but it is unclear which specific intestinal bacteria predispose to and which protect from IBD and how they are regulated. Peptidoglycan recognition proteins (Pglyrps) are antibacterial, participate in maintaining intestinal microflora, and modulate inflammatory responses. Mice deficient in any one of the four Pglyrp genes are more sensitive to dextran sulfate sodium (DSS)-induced colitis, and stools from Pglyrp-deficient mice transferred to wild type (WT) germ-free mice predispose them to much more severe colitis than stools from WT mice. However, the identities of these Pglyrp-regulated bacteria that predispose Pglyrp-deficient mice to colitis or protect WT mice from colitis are not known. Here we identified significant changes in β-diversity of stool bacteria in Pglyrp-deficient mice compared with WT mice. The most consistent changes in microbiome in all Pglyrp-deficient mice were in Bacteroidales, from which we selected four species, two with increased abundance (Prevotella falsenii and Parabacteroides distasonis) and two with decreased abundance (Bacteroides eggerthii and Alistipes finegoldii). We then gavaged WT mice with stock type strains of these species to test the hypothesis that they predispose to or protect from DSS-induced colitis. P. falsenii, P. distasonis, and B. eggerthii all enhanced DSS-induced colitis in both WT mice with otherwise undisturbed intestinal microflora and in WT mice with antibiotic-depleted intestinal microflora. By contrast, A. finegoldii (which is the most abundant species in WT mice) attenuated DSS-induced colitis both in WT mice with otherwise undisturbed intestinal microflora and in WT mice with antibiotic-depleted intestinal microflora, similar to the colitis protective effect of the entire normal microflora. These results identify P. falsenii, P. distasonis, and B. eggerthii as colitis-promoting species and A. finegoldii as colitis-protective species.

  4. Chemically induced magnetism in atomically precise gold clusters.

    Science.gov (United States)

    Krishna, Katla Sai; Tarakeshwar, Pilarisetty; Mujica, Vladimiro; Kumar, Challa S S R

    2014-03-12

    Comparative theoretical and experimental investigations are reported into chemically induced magnetism in atomically-precise, ligand-stabilized gold clusters Au25 , Au38 and Au55 . The results indicate that [Au25 (PPh3 )10 (SC12 H25 )5 Cl2 ](2+) and Au38 (SC12 H25 )24 are diamagnetic, Au25 (SC2 H4 Ph)18 is paramagnetic, and Au55 (PPh3 )12 Cl6 , is ferromagnetic at room temperature. Understanding the magnetic properties resulting from quantum size effects in such atomically precise gold clusters could lead to new fundamental discoveries and applications.

  5. Modulation of Colitis-associated Colon Tumorigenesis by Baicalein and Betaine.

    Science.gov (United States)

    Kim, Dong Hwan; Sung, Bokyung; Chung, Hae Young; Kim, Nam Deuk

    2014-09-01

    In this review, we will summarize the current understanding of modulation of colitis-associated colon tumorigenesis by two natural products, baicalein and betaine, which have anti-inflammatory activities. Baicalein and betaine have been shown to provide various health benefits to organism in many ways. Baicalein is a phenolic flavonoid derived originally from the root of Scutellaria baicalensis Georgi. From ancient times, baicalein has widely been used in oriental medicines as an anti-inflammatory and anti-cancer therapy. Betaine, trimethylglycine, is an essential biochemical molecule of the methionine/homocysteine cycle and is synthesized by conversion of choline. Betaine is an important human nutrient obtained from various foods including sugar beet and lycium. Betaine has provided various health benefits including disease prevention. However, the action mechanisms of their activity remain poorly understood. Recent studies reported the effects of baicalein and betaine on cytotoxicity against colon cancer cells and chemically induced colitis-associated colon tumorigenesis in mice. Administrations of baicalein and betaine containing diets significantly inhibited the incidence of tumors and hyperplasia with down-regulation of inflammation. Therefore, baicalein and betaine might be applicable to the prevention of inflammation-associated colon carcinogenesis. PMID:25337584

  6. Altered response to hydrogen sulphide during experimental colitis in rats.

    Science.gov (United States)

    Steidle, J; Würner, L; Diener, M

    2012-09-10

    Hydrogen sulphide (H(2) S) is produced in the intestine by sulphate-reducing bacteria and during metabolism of L-cysteine within the mucosa. This gasotransmitter induces anion secretion by stimulating enteric neurons and by a direct effect on epithelial cells. As H(2) S is discussed to exert both pro- and anti-inflammatory actions, we aimed to investigate the role of H(2) S during experimental colitis by comparing the effects of blockade of H(2) S-forming endogenous enzymes with the effect of a S-reduced diet to diminish microbial production of H(2) S. Rectal application of trinitrobenzenesulfonic acid (TNBS) was used to induce chronic colitis. The level of inflammation was assessed macroscopically and histologically. In Ussing chamber experiments, colonic specimens from TNBS-treated animals exhibited a higher tissue conductance, that is, a higher epithelial permeability, and a slightly reduced basal short-circuit current (a measure of net ion transport) in relation to non-inflamed control tissue. Analgetic treatment with flupirtine, a central antinociceptive analgetic, did not interfere with the induction of the inflammatory response so that all animals were treated with flupirtine to reduce pain and distress during the development of colitis. The secretory response evoked by an exogenous H(2) S donor, NaHS, was significantly decreased after induction of colitis, whereas the response to Ca(2+) - or cAMP-dependent secretagogues was unaltered. This downregulation was not observed in the colitis group fed on a S-reduced diet. The decreased NaHS response indicates a desensitization of the tissue by inflammation, which might be explained by an upregulation of colonic H(2) S production as described in some models of inflammation. PMID:22963333

  7. 3-(2-Oxo-2-phenylethylidene)-2,3,6,7-tetrahydro-1H-pyrazino[2,1-a]isoquinolin-4(11bH)-one (compound 1), a novel potent Nrf2/ARE inducer, protects against DSS-induced colitis via inhibiting NLRP3 inflammasome.

    Science.gov (United States)

    Wang, Yajing; Wang, Hong; Qian, Chen; Tang, Jingjing; Zhou, Wei; Liu, Xiuting; You, Qidong; Hu, Rong

    2016-02-01

    NLRP3 inflammasome is a key component of the inflammatory process and its dysregulation contributes to IBD for its ability to induce IL-1β release. Previously, we reported that a novel small molecular activator of Nrf2, 3-(2-oxo-2-phenylethylidene)-2,3,6,7-tetrahydro-1H-pyrazino-[2,1-a]isoquinolin-4(11bH)-one (compound 1) can prevent the development of colorectal adenomas in AOM-DSS models. Here we further investigated the anti-inflammatory effect of compound 1 in DSS-induced colitis in C57BL/6 and NLRP3(-/-) mice, and revealed the possible modulation by compound 1 of NLRP3 inflammasome-mediated IL-1β release from macrophages. In C57BL/6 mice, oral administration of compound 1 significantly attenuated DSS-induced colonic pathological damage, remarkably inhibited inflammatory cells infiltration and decreased myeloperoxidase (MPO) and IL-1β secretion in colons. In contrast, mice deficient for NLRP3 were less sensitive to DSS-induced acute colitis, and compound 1 treatment exerted no protective effect on DSS-induced intestinal inflammation in NLRP3(-/-) mice. The protective effect of compound 1 may be attributed to its inhibition of NLRP3 inflammasome and Nrf2 activation in colons. Furthermore, compound 1, as a small molecular activator of Nrf2, significantly inhibited NLRP3 inflammasome activation in both THP-1 derived macrophages and bone-marrow derived macrophages, as indicated by reduced expression of NLRP3 and cleaved caspase-1, and lowered IL-1β secretion. Finally, compound 1-induced NLRP3 inflammasome inhibition is through blocking NLRP3 priming step and dependent on Nrf2 activation. Taken together, our findings demonstrate that compound 1 might be a potential agent for the treatment of IBD by targeting Nrf2 and NLRP3 inflammasome.

  8. Kolorektal cancerudvikling ved colitis ulcerosa

    DEFF Research Database (Denmark)

    Kallesøe, Jane; Langholz, E.; Frisch, Morten;

    2010-01-01

    Ulcerative colitis (UC) is believed to carry a predisposition to colorectal cancer (CRC) development. International clinical guidelines suggest that UC patients should have a colonoscopy performed every year or up to every third year from approximately eight years after diagnosis for early...

  9. Mucosal healing in ulcerative colitis

    DEFF Research Database (Denmark)

    Seidelin, Jakob Benedict; Coskun, Mehmet; Nielsen, Ole Haagen

    2013-01-01

    Ulcerative colitis (UC) is a colonic inflammatory condition with a substantial impact on the quality of life of affected persons. The disease carries a cumulative risk of need of colectomy of 20-30% and an estimated cumulative risk of colorectal cancer of 18% after 30 years of disease duration...

  10. Anorexia nervosa and necrotizing colitis.

    OpenAIRE

    Kaye, J. C.; Madden, M V; Leaper, D J

    1985-01-01

    Anorexia nervosa is associated with a mortality approaching 5% in patients severely enough affected to warrant hospital care (Hsu, 1980). The main causes of death are inanition, electrolyte disturbances or suicide. We report here a case of necrotizing colitis associated with anorexia nervosa, an association which has not been described previously.

  11. Puberty Is Delayed in Male Mice With Dextran Sodium Sulfate Colitis Out of Proportion to Changes in Food Intake, Body Weight, and Serum Levels of Leptin

    OpenAIRE

    DeBoer, Mark D.; Li, Yongli

    2011-01-01

    In boys, inflammatory bowel disease often results in delayed puberty associated with decreased bone mineral density and decreased linear growth. Our goal was to investigate whether pubertal timing and levels of leptin differed between prepubertal male mice with colitis and food-restricted (FR) mice maintained at a similar weight. We induced colitis in 32-d-old male mice using dextran sodium sulfate (DSS), resulting in 10 d of worsening colitis. We followed up these mice for separation of the ...

  12. A high-throughput chemically induced inflammation assay in zebrafish

    Directory of Open Access Journals (Sweden)

    Liebel Urban

    2010-12-01

    Full Text Available Abstract Background Studies on innate immunity have benefited from the introduction of zebrafish as a model system. Transgenic fish expressing fluorescent proteins in leukocyte populations allow direct, quantitative visualization of an inflammatory response in vivo. It has been proposed that this animal model can be used for high-throughput screens aimed at the identification of novel immunomodulatory lead compounds. However, current assays require invasive manipulation of fish individually, thus preventing high-content screening. Results Here we show that specific, noninvasive damage to lateral line neuromast cells can induce a robust acute inflammatory response. Exposure of fish larvae to sublethal concentrations of copper sulfate selectively damages the sensory hair cell population inducing infiltration of leukocytes to neuromasts within 20 minutes. Inflammation can be assayed in real time using transgenic fish expressing fluorescent proteins in leukocytes or by histochemical assays in fixed larvae. We demonstrate the usefulness of this method for chemical and genetic screens to detect the effect of immunomodulatory compounds and mutations affecting the leukocyte response. Moreover, we transformed the assay into a high-throughput screening method by using a customized automated imaging and processing system that quantifies the magnitude of the inflammatory reaction. Conclusions This approach allows rapid screening of thousands of compounds or mutagenized zebrafish for effects on inflammation and enables the identification of novel players in the regulation of innate immunity and potential lead compounds toward new immunomodulatory therapies. We have called this method the chemically induced inflammation assay, or ChIn assay. See Commentary article: http://www.biomedcentral.com/1741-7007/8/148.

  13. Modeling drug- and chemical- induced hepatotoxicity with systems biology approaches

    Directory of Open Access Journals (Sweden)

    Sudin eBhattacharya

    2012-12-01

    Full Text Available We provide an overview of computational systems biology approaches as applied to the study of chemical- and drug-induced toxicity. The concept of ‘toxicity pathways’ is described in the context of the 2007 US National Academies of Science report, Toxicity testing in the 21st Century: A Vision and A Strategy. Pathway mapping and modeling based on network biology concepts are a key component of the vision laid out in this report for a more biologically-based analysis of dose-response behavior and the safety of chemicals and drugs. We focus on toxicity of the liver (hepatotoxicity – a complex phenotypic response with contributions from a number of different cell types and biological processes. We describe three case studies of complementary multi-scale computational modeling approaches to understand perturbation of toxicity pathways in the human liver as a result of exposure to environmental contaminants and specific drugs. One approach involves development of a spatial, multicellular virtual tissue model of the liver lobule that combines molecular circuits in individual hepatocytes with cell-cell interactions and blood-mediated transport of toxicants through hepatic sinusoids, to enable quantitative, mechanistic prediction of hepatic dose-response for activation of the AhR toxicity pathway. Simultaneously, methods are being developing to extract quantitative maps of intracellular signaling and transcriptional regulatory networks perturbed by environmental contaminants, using a combination of gene expression and genome-wide protein-DNA interaction data. A predictive physiological model (DILIsymTM to understand drug-induced liver injury (DILI, the most common adverse event leading to termination of clinical development programs and regulatory actions on drugs, is also described. The model initially focuses on reactive metabolite-induced DILI in response to administration of acetaminophen, and spans multiple biological scales.

  14. CD3 immunohistochemical staining in diagnosis of lymphocytic colitis

    DEFF Research Database (Denmark)

    Fiehn, Anne-Marie Kanstrup; Engel, Ulla; Holck, Susanne;

    2016-01-01

    Microscopic colitis (MC) is a common cause of chronic watery diarrhea. Traditionally, MC encompasses the 2 subgroups lymphocytic colitis (LC) and collagenous colitis, but recently, an additional subgroup, MC incomplete, has been introduced. Distinguishing between the subgroups relies exclusively...

  15. Chemically Induced and Light-Independent Cryptochrome Photoreceptor Activation

    Institute of Scientific and Technical Information of China (English)

    Gesa Rosenfeldt; Rafael Mu(n)oz Viana; Henning D.Mootz; Albrecht G.Von Arnim; Alfred Batschauer

    2008-01-01

    The cryptochrome photoreceptors of higher plants are dimeric proteins. Their N-terminal photosensory domain mediates dimerization, and the unique C-terminal extension (CCT) mediates signaling. We made use of the human FK506-binding protein (FKBP) that binds with high affinity to rapamycin or rapamycin analogs (rapalogs). The FKBP-rapamycin complex is recognized by another protein, FRB, thus allowing rapamycin-induced dimerization of two target proteins. Here we demonstrate by bioluminescence resonance energy transfer (BRET) assays the applicability of this regulated dimerization system to plants. Furthermore, we show that fusion proteins consisting of the C-terminal domain of Arabidopsis cryptochrome 2 fused to FKBP and FRB and coexpressed in Arabidopsis cells specifically induce the expression of cryptochrome-controlled reporter and endogenous genes in darkness upon incubation with the rapalog. These results demonstrate that the activation of cryptochrome signal transduction can be chemically induced in a dose-dependent fashion and uncoupled from the light signal, and provide the groundwork for gain-of-function experiments to study specifically the role of photoreceptors in darkness or in signaling cross-talk even under light conditions that activate members of all photoreceptor families.

  16. Visceral hypersensitivity and altered colonic motility after subsidence of inflammation in a rat model of colitis

    Institute of Scientific and Technical Information of China (English)

    Jun-Ho La; Tae-Wan Kim; Tae-Sik Sung; Jeoung-Woo Kang; Kyun-Ju Kim; Il-Suk Yang

    2003-01-01

    AIM: Irritable bowel syndrome (IBS) is a functional bowel disorder characterized by visceral hypersensitivity and altered bowel motility. There is increasing evidence suggesting the role of inflammation in the pathogenesis of IBS, which addresses the possibility that formerly established rat model of colitis could be used as an TBS model after the inflammation subsided.METHODS: Colitis was induced by intracolonic instillation of 4 % acetic acid in male Sprague-Dawley rats. The extent of inflammation was assessed by histological examination and myeloperoxidase (MPO) activity assay. After subsidence of colitis, the rats were subjected to rectal distension and restraint stress, then the abdominal withdrawal reflex and the number of stress-induced fecal output were measured,respectively.RESULTS: At 2 days post-induction of colitis, the colon showed characteristic inflammatory changes in histology and 8-fold increase in MPO activity. At 7 days post-induction of colitis, the histological features and MPO activity returned to normal. The rats at 7 days post-induction of colitis showed hypersensitive response to rectal distension without an accompaning change in rectal compliance, and defecated more stools than control animals when under stress.CONCLUSION: These results concur largely with the characteristic features of IBS, visceral hypersensitivity and altered defecation pattern in the absence of detectable disease, suggesting that this animal model is a methodologically convenient and useful model for studying a subset of IBS.

  17. Clear cell colitis: A form of microscopic colitis in children

    Institute of Scientific and Technical Information of China (English)

    Jan J(o)zefczuk; Bogdan Marian Wozniewicz

    2008-01-01

    AIM: To describe a new clinical and pathological subtype of microscopic colitis in children.METHODS: A selected group of children with abdominal pain, constipation and/or diarrhoea showing discrete or no macroscopic abnormalities on endoscopy was described.RESULTS: Multiple biopsies of colon showed large mononuclear clear cells in lamina propria of mucous membrane provided that good quality histological sections were performed and observed under a higher magnification. Otherwise, they could be misinterpreted as artefacts. Their presence in routine histology might suggest a systemic storage disease (Whipple's disease), and neuronal intestine dysplasia.Using immunohistochemical staining and electron microscopy we confirmed their origin from CD68 positive mononuclear macrophages.CONCLUSION: The presence of large clear cells is a constant microscopic feature. Failure of transient large bowel stationary macrophages plays a role in the pathogenesis of this benign microscopic clear cell colitis,sometimes coexisting with allergy.

  18. Factor XIII Transglutaminase Supports the Resolution of Mucosal Damage in Experimental Colitis.

    Directory of Open Access Journals (Sweden)

    Christina Andersson

    Full Text Available The thrombin-activated transglutaminase factor XIII (FXIII that covalently crosslinks and stablizes provisional fibrin matrices is also thought to support endothelial and epithelial barrier function and to control inflammatory processes. Here, gene-targeted mice lacking the FXIII catalytic A subunit were employed to directly test the hypothesis that FXIII limits colonic pathologies associated with experimental colitis. Wildtype (WT and FXIII-/- mice were found to be comparable in their initial development of mucosal damage following exposure to dextran sulfate sodium (DSS challenge. However, unlike FXIII-sufficient mice, FXIII-deficient cohorts failed to efficiently resolve colonic inflammatory pathologies and mucosal damage following withdrawal of DSS. Consistent with prior evidence of ongoing coagulation factor activation and consumption in individuals with active colitis, plasma FXIII levels were markedly decreased in colitis-challenged WT mice. Treatment of colitis-challenged mice with recombinant human FXIII-A zymogen significantly mitigated weight loss, intestinal bleeding, and diarrhea, regardless of whether cohorts were FXIII-sufficient or were genetically devoid of FXIII. Similarly, both qualitative and quantitative microscopic analyses of colonic tissues revealed that exogenous FXIII improved the resolution of multiple colitis disease parameters in both FXIII-/- and WT mice. The most striking differences were seen in the resolution of mucosal ulceration, the most severe histopathological manifestation of DSS-induced colitis. These findings directly demonstrate that FXIII is a significant determinant of mucosal healing and clinical outcome following inflammatory colitis induced mucosal injury and provide a proof-of-principle that clinical interventions supporting FXIII activity may be a means to limit colitis pathology and improve resolution of mucosal damage.

  19. Factor XIII Transglutaminase Supports the Resolution of Mucosal Damage in Experimental Colitis

    Science.gov (United States)

    Andersson, Christina; Kvist, Peter H.; McElhinney, Kathryn; Baylis, Richard; Gram, Luise K.; Pelzer, Hermann; Lauritzen, Brian; Holm, Thomas L.; Hogan, Simon; Wu, David; Turpin, Brian; Miller, Whitney; Palumbo, Joseph S.

    2015-01-01

    The thrombin-activated transglutaminase factor XIII (FXIII) that covalently crosslinks and stablizes provisional fibrin matrices is also thought to support endothelial and epithelial barrier function and to control inflammatory processes. Here, gene-targeted mice lacking the FXIII catalytic A subunit were employed to directly test the hypothesis that FXIII limits colonic pathologies associated with experimental colitis. Wildtype (WT) and FXIII-/- mice were found to be comparable in their initial development of mucosal damage following exposure to dextran sulfate sodium (DSS) challenge. However, unlike FXIII-sufficient mice, FXIII-deficient cohorts failed to efficiently resolve colonic inflammatory pathologies and mucosal damage following withdrawal of DSS. Consistent with prior evidence of ongoing coagulation factor activation and consumption in individuals with active colitis, plasma FXIII levels were markedly decreased in colitis-challenged WT mice. Treatment of colitis-challenged mice with recombinant human FXIII-A zymogen significantly mitigated weight loss, intestinal bleeding, and diarrhea, regardless of whether cohorts were FXIII-sufficient or were genetically devoid of FXIII. Similarly, both qualitative and quantitative microscopic analyses of colonic tissues revealed that exogenous FXIII improved the resolution of multiple colitis disease parameters in both FXIII-/- and WT mice. The most striking differences were seen in the resolution of mucosal ulceration, the most severe histopathological manifestation of DSS-induced colitis. These findings directly demonstrate that FXIII is a significant determinant of mucosal healing and clinical outcome following inflammatory colitis induced mucosal injury and provide a proof-of-principle that clinical interventions supporting FXIII activity may be a means to limit colitis pathology and improve resolution of mucosal damage. PMID:26098308

  20. Non-Hematopoietic β-Arrestin1 Confers Protection Against Experimental Colitis.

    Science.gov (United States)

    Lee, Taehyung; Lee, Eunhee; Arrollo, David; Lucas, Peter C; Parameswaran, Narayanan

    2016-05-01

    β-Arrestins are multifunctional scaffolding proteins that modulate G protein-coupled receptor (GPCR)-dependent and -independent cell signaling pathways in various types of cells. We recently demonstrated that β-arrestin1 (β-arr1) deficiency strikingly attenuates dextran sodium sulfate (DSS)-induced colitis in mice. Since DSS-induced colitis is in part dependent on gut epithelial injury, we examined the role of β-arr1 in intestinal epithelial cells (IECs) using a colon epithelial cell line, SW480 cells. Surprisingly, we found that knockdown of β-arr1 in SW480 cells enhanced epithelial cell death via a caspase-3-dependent process. To understand the in vivo relevance and potential cell type-specific role of β-arr1 in colitis development, we generated bone marrow chimeras with β-arr1 deficiency in either the hematopoietic or non-hematopoietic compartment. Reconstituted chimeric mice were then subjected to DSS-induced colitis. Similar to our previous findings, β-arr1 deficiency in the hematopoietic compartment protected mice from DSS-induced colitis. However, consistent with the role of β-arr1 in epithelial apoptosis in vitro, non-hematopoietic β-arr1 deficiency led to an exacerbated colitis phenotype. To further understand signaling mechanisms, we examined the effect of β-arr1 on TNF-α-mediated NFκB and MAPK pathways. Our results demonstrate that β-arr1 has a critical role in modulating ERK, JNK and p38 MAPK pathways mediated by TNF-α in IECs. Together, our results show that β-arr1-dependent signaling in hematopoietic and non-hematopoietic cells differentially regulates colitis pathogenesis and further demonstrates that β-arr1 in epithelial cells inhibits TNF-α-induced cell death pathways.

  1. β-lactam-associated eosinophilic colitis.

    Science.gov (United States)

    Mogilevski, Tamara; Nickless, David; Hume, Sam

    2015-01-01

    A 42-year-old man with a history of childhood asthma presented with a 2-week history of watery diarrhoea and marked peripheral eosinophilia in the setting of recent use of cephalexin. His colonoscopy revealed patchy colitis. Biopsies were consistent with eosinophilic colitis. Two months later he received a course of amoxicillin resulting in recurrence of peripheral eosinophilia. Given the time-frame of β-lactam administration to symptom onset and elimination of all other precipitating causes, he was diagnosed with β-lactam-associated eosinophilic colitis. The patient's symptoms resolved and peripheral eosinophil count decreased with no specific treatment. Eosinophilic colitis is a rare heterogeneous condition, the pathogenesis of which is likely to be an interplay between environmental and genetic factors. It can be secondary to a helminthic infection or a drug reaction and has been associated with ulcerative colitis. If secondary causes of eosinophilic colitis have been excluded, the mainstay of treatment is with corticosteroids. PMID:26106168

  2. Colitis is associated with a loss of intestinofugal neurons

    OpenAIRE

    Linden, David R.

    2012-01-01

    Intestinofugal neurons sense and receive information regarding mechanical distension of the bowel and transmit this information to postganglionic sympathetic neurons in the prevertebral ganglia. Previous studies have demonstrated that trinitrobenzene sulfonic acid (TNBS)-induced colitis is associated with a loss of myenteric neurons that occurs within the first 12 h following the inflammatory insult. The purpose of this study was to test the hypothesis that intestinofugal neurons are among th...

  3. Damage to the Enteric Nervous System in Experimental Colitis

    OpenAIRE

    Sanovic, Srdan; Lamb, Damian P.; Blennerhassett, Michael G

    1999-01-01

    Inflammation of the intestine causes pain and altered motility, at least in part through effects on the enteric nervous system. While these changes may be reversed with healing, permanent damage may contribute to inflammatory bowel disease (IBD) and post-enteritis irritable bowel syndrome. Since little information exists, we induced colitis in male Sprague-Dawley rats with dinitrobenzene sulfonic acid and used immunocytochemistry to examine the number and distribution of enteric neurons at ti...

  4. Surveillance for colitis-associated colon neoplasia

    Institute of Scientific and Technical Information of China (English)

    Hugh; James; Freeman

    2010-01-01

    The risk of developing colon cancer is increased in colitis patients, particularly if the disease is extensive and its duration long-standing. Endoscopic guidelines have been developed with the goal of detecting early neoplastic changes prior to development of advanced malignancy. Unfortunately, the natural history of this superimposed neoplastic process in colitis appears to be very heterogeneous and poorly understood. Moreover, there are numerous confounding variables in colitis patients that limit accura...

  5. Light-induced chemical vapour deposition painting with titanium dioxide

    Science.gov (United States)

    Halary-Wagner, E.; Bret, T.; Hoffmann, P.

    2003-03-01

    Light-induced chemical vapour deposits of titanium dioxide are obtained from titanium tetra-isopropoxide (TTIP) in an oxygen and nitrogen atmosphere with a long pulse (250 ns) 308 nm XeCl excimer laser using a mask projection set-up. The demonstrated advantages of this technique are: (i) selective area deposition, (ii) precise control of the deposited thickness and (iii) low temperature deposition, enabling to use a wide range of substrates. A revolving mask system enables, in a single reactor load, to deposit shapes of controlled heights, which overlap to build up a complex pattern. Interferential multi-coloured deposits are achieved, and the process limitations (available colours and resolution) are discussed.

  6. Quantum measurement corrections to chemically induced dynamic nuclear polarization

    CERN Document Server

    Kominis, I K

    2013-01-01

    Chemically induced dynamic nuclear polarization has emerged as a universal signature of spin order in photosynthetic reaction centers. Such polarization, significantly enhanced above thermal equilibrium, is known to result from the nuclear spin sorting inherent in the radical pair mechanism underlying long-lived charge-separated states in photosynthetic reaction centers. We will here show that the recently understood fundamental quantum dynamics of radical-ion-pair reactions open up a new and completely unexpected venue towards obtaining CIDNP signals. The fundamental decoherence mechanism inherent in the recombination process of radical pairs is shown to produce nuclear spin polarizations on the order of $10^4$ times or more higher than thermal equilibrium values at low fields relevant to natural photosynthesis in earth's magnetic field. This opens up the possibility of a fundamentally new exploration of the biological significance of high nuclear polarizations in photosynthesis.

  7. COMPARISION BETWEEN THE EFFECT OF AQUEOUS AND METHANOLIC EXTRACTS OF HOLARRHENA ANTIDYSENTERICA BARK AGAINST EXPERIMENTALLY INDUCED INFLAMMATORY BOWEL DISEASE

    Directory of Open Access Journals (Sweden)

    Darji Vinay C.

    2013-01-01

    Full Text Available It has been demonstrated that Holarrhena antidysenterica Wall. (Apocynaceae is useful as an adjunctive therapy for Inflammatory bowel disease (IBD. However, its effect on ulcerative colitis has not been investigated. In the present study, aqueous and methanolic extracts of Holarrhena antidysenterica were tested for 2, 4 - dinitro benzene sulfonic acid (DNBS induced colitis, and antioxidant activity were evaluated to clarify possible mode of action. Male albino wistar rats were randomly divided into six groups: Normal control (Group I, Vehical contol (Group II, colitis induced by DNBS without any therapy (Group III, colitis treated with standard Dexamethasone (Group IV, colitis treated with methanolic extract of test drug Holarrhena antidysenterica (Group V, colitis treated with aqueous extract of test drug Holarrhena antidysenterica (Group VI. Treatment was given for 18 days. Rats were sacrificed on the 18th day after the procedure and the levels of Malondialdehyde (MDA, Nitric oxide (NO, Reduced gluthathione (GSH, Superoxide dismutase (SOD were measured in the isolated colon tissue. MDA & NO levels in colon tissue homogenate were decreased while SOD & GSH level were increased in group IV, V & VI as compared to those of Group III. There was also increase in food intake, water intake & decreased colon weight in Group IV, V & VI as compared to Group III. There was also improvement in inflammatory indices of colon mucosal damage index (CMDI & disease activity index (DAI & histopathology of Group IV, V & VI as compared to those of group III. Levels of all the chemical parameters, Physical parameters & Histological parameters were significantly improved after the treatment with methanolic extract of test drug compared to aqueous extract of test drug. Treatment with aqueous extract also improves the colitis condition but it was not significantly improved by it as compared to methanolic extract of test drug. The results of our study suggest that

  8. Cyclooxygenase-2 immunoreactivity in collagenous colitis

    DEFF Research Database (Denmark)

    Wildt, Signe; Rumessen, Jüri J; Csillag, Claudio;

    2009-01-01

    Collagenous colitis (CC) is an inflammatory bowel disease of unknown aetiology and pathogenesis. In ulcerative colitis and Crohn's disease, prostaglandins may be involved in the pathogenesis of inflammation, and increased expression of cyclo-oxygenase-2 (COX-2) has been detected. The purpose...... with samples from eight normal controls, and samples from eight patients with ulcerative colitis or Crohn's disease. Specimens from patients with CC expressed COX-2 protein in increased amounts compared with controls, but similar to patients with ulcerative colitis and Crohn's disease. COX-2 expression...

  9. Autoimmune hepatitis in association with lymphocytic colitis.

    LENUS (Irish Health Repository)

    Cronin, Edmond M

    2012-02-03

    Autoimmune hepatitis is a rare, chronic inflammatory disorder which has been associated with a number of other auto-immune conditions. However, there are no reports in the medical literature of an association with microscopic (lymphocytic) colitis. We report the case of a 53-year-old woman with several autoimmune conditions, including lymphocytic colitis, who presented with an acute hepatitis. On the basis of the clinical features, serology, and histopathology, we diagnosed autoimmune hepatitis. To our knowledge, this is the first report of autoimmune hepatitis in association with lymphocytic colitis, and lends support to the theory of an autoimmune etiology for lymphocytic colitis.

  10. The misdiagnosis of ischaemic colitis

    Energy Technology Data Exchange (ETDEWEB)

    Rudd, Joanne [Department of Radiology, West Suffolk Hospital, Hardwick Lane, Bury St Edmunds, Suffolk IP33 2QZ (United Kingdom)]. E-mail: joanne.rudd@wsh.nhs.uk

    2006-11-15

    This case study followed the pathway taken by an elderly patient who presented as an emergency with rectal bleeding. Views obtained of the colon by flexible sigmoidoscopy suggested an initial diagnosis of colorectal carcinoma but this proved to be incorrect. It was a combination of the histology obtained from the initial and subsequent endoscopies, barium enema and the clinical history that finally gave rise to the correct diagnosis of ischaemic colitis. Opinion is currently divided as to whether sigmoidoscopy or colonoscopy is the most appropriate test for those patients presenting with rectal bleeding. Ischaemic colitis is a disease that can present with many differing symptoms depending on the degree of severity of the ischaemia.

  11. Salmon cartilage proteoglycan suppresses mouse experimental colitis through induction of Foxp3{sup +} regulatory T cells

    Energy Technology Data Exchange (ETDEWEB)

    Mitsui, Toshihito [Department of Microbiology and Immunology, Hirosaki University Graduate School of Medicine, Zaifu-cho 5, Hirosaki, Aomori 036-8562 (Japan); Department of Digestive Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036-8562 (Japan); Sashinami, Hiroshi [Department of Microbiology and Immunology, Hirosaki University Graduate School of Medicine, Zaifu-cho 5, Hirosaki, Aomori 036-8562 (Japan); Sato, Fuyuki; Kijima, Hiroshi [Department of Pathology and Bioscience, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036-8562 (Japan); Ishiguro, Yoh; Fukuda, Shinsaku [Department of Digestive Internal Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036-8562 (Japan); Yoshihara, Shuichi [Department of Glycomedicine, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036-8562 (Japan); Hakamada, Ken-Ichi [Department of Digestive Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036-8562 (Japan); Nakane, Akio, E-mail: a27k03n0@cc.hirosaki-u.ac.jp [Department of Microbiology and Immunology, Hirosaki University Graduate School of Medicine, Zaifu-cho 5, Hirosaki, Aomori 036-8562 (Japan)

    2010-11-12

    Research highlights: {yields} Salmon proteoglycan suppresses IL-10{sup -/-} cell transfer-induced colitis progression. {yields} Salmon proteoglycan suppresses Th1- and Th17-related factors in colitis mice. {yields} Salmon proteoglycan enhances Foxp3 expression. -- Abstract: Proteoglycans (PGs) are complex glycohydrates which are widely distributed in extracellular matrix (ECM). PGs are involved in the construction of ECM, cell proliferation and differentiation. ECM components are involved in transduction of proinflammatory responses, but it is still unknown whether PGs are involved in inflammatory response. In this study, we investigated the effect of PG extracted from salmon cartilage on the progression of experimental colitis-induced in severe combined immunodeficiency mice by cell transfer from interleukin-10 (IL-10){sup -/-} mice. IL-10{sup -/-} cell-transferred mice showed weight loss, colon shortening and histological appearance of mild colitis. Daily oral administration of PG attenuated the clinical progression of colitis in a dose-dependent manner. Colitis-induced mice showed the elevated expression of IFN-{gamma}, IL-12, TNF-{alpha}, IL-21, IL-23p19, IL-6, IL-17A and retinoic acid-related orphan receptor {gamma}t (ROR{gamma}t) in lamina propria mononuclear cells (LPMCs) and oral administration of PG suppressed the expression of these factors. Conversely, expression of Foxp3 that induces CD4{sup +}CD25{sup +} regulatory T cells in LPMCs was enhanced by PG administration. These findings suggested that salmon PG attenuated the progression of colitis due to suppression of inflammatory response by enhancement of regulatory T cell induction.

  12. Charged impurity-induced scatterings in chemical vapor deposited graphene

    Science.gov (United States)

    Li, Ming-Yang; Tang, Chiu-Chun; Ling, D. C.; Li, L. J.; Chi, C. C.; Chen, Jeng-Chung

    2013-12-01

    We investigate the effects of defect scatterings on the electric transport properties of chemical vapor deposited (CVD) graphene by measuring the carrier density dependence of the magneto-conductivity. To clarify the dominant scattering mechanism, we perform extensive measurements on large-area samples with different mobility to exclude the edge effect. We analyze our data with the major scattering mechanisms such as short-range static scatters, short-range screened Coulomb disorders, and weak-localization (WL). We establish that the charged impurities are the predominant scatters because there is a strong correlation between the mobility and the charge impurity density. Near the charge neutral point (CNP), the electron-hole puddles that are induced by the charged impurities enhance the inter-valley scattering, which is favorable for WL observations. Away from the CNP, the charged-impurity-induced scattering is weak because of the effective screening by the charge carriers. As a result, the local static structural defects govern the charge transport. Our findings provide compelling evidence for understanding the scattering mechanisms in graphene and pave the way for the improvement of fabrication techniques to achieve high-quality CVD graphene.

  13. Turner Syndrome with Ulcerative Colitis

    OpenAIRE

    Hyodo, Hiromi; TOMITA, Yuichiro; Hirai, Kohta; HIRAKAWA, Hitoshi; Ueno, Shigeru; Ishiguro, Hiroyuki

    2009-01-01

    Turner syndrome is a chromosomal disease frequently associated with autoimmune disorders including diabetes mellitus, thyroid disease and inflammatory bowel disease (IBD). Although the etiology of IBD has not been fully elucidated, genetic analysis has recently revealed several susceptibility genes. Recently, cases with Turner syndrome associated with IBD have been reported. We report here a 13-yr-old girl with Turner syndrome associated with ulcerative colitis. The patient was undergoing gro...

  14. Ulcerative colitis after Cytomegalovirus Infection

    Directory of Open Access Journals (Sweden)

    Mohammad Aminianfar

    2014-06-01

    Full Text Available A 21 years old man has been complained of bloody diarrhea, liquid stool containing blood, pus, and fecal matter and crampy abdominal pain from four monthes ago. Ulcerative colitis relies upon the patient's history, clinical symptoms, sigmoidoscopic appearance and histology of colonic biopsy specimens. Treatment of patient started with high dose dexamethasone and prednisolone, asacole, suppository, metronidazole. Patient’s condition not improved and patient admitted in hospital. High dose prednisolone, azathioprine, sulfasalazine and folic acid were given.

  15. Colitis after polytrauma: Case report

    OpenAIRE

    William E. Carter, MD, MPH; Isaac A. Darko, MD; Priya Chandan, MD, MPH; Ajit B. Pai, MD

    2014-01-01

    Across the medical literature, delayed diagnosis and treatment leads to more costly and worse outcomes. Rehabilitation patients, especially those with polytrauma, often have a complex mixture of medical, social, and psychological health problems that can impair effective diagnosis and treatment. The case presentation describes the procession toward the diagnosis of ulcerative colitis in a preinjury asymptomatic male, suggesting a potential mechanism for its emergence and describing the effect...

  16. Effects of the immunomodulator, VGX-1027, in endotoxin-induced uveitis in Lewis rats

    DEFF Research Database (Denmark)

    Mangano, K; Sardesai, N Y; Quattrocchi, C;

    2008-01-01

    VGX-1027 is a novel, low molecular weight, immunomodulatory compound that has shown efficacy against a variety of immuno-inflammatory disease models in animals including autoimmune diabetes in NOD mice, collagen-induced arthritis and chemically induced inflammatory colitis. Here, we have studied ...... the effects of VGX-1027 on the development of endotoxin-induced uveitis (EIU) in male Lewis rats, as a model of inflammatory ocular diseases in humans....

  17. Effects of the immunomodulator, VGX-1027, in endotoxin-induced uveitis in Lewis rats

    DEFF Research Database (Denmark)

    Mangano, K; Sardesai, N Y; Quattrocchi, C;

    2008-01-01

    VGX-1027 is a novel, low molecular weight, immunomodulatory compound that has shown efficacy against a variety of immuno-inflammatory disease models in animals including autoimmune diabetes in NOD mice, collagen-induced arthritis and chemically induced inflammatory colitis. Here, we have studied...... the effects of VGX-1027 on the development of endotoxin-induced uveitis (EIU) in male Lewis rats, as a model of inflammatory ocular diseases in humans....

  18. Protective Effect of Laminaria japonica with Probiotics on Murine Colitis

    Directory of Open Access Journals (Sweden)

    Seok-Jae Ko

    2014-01-01

    Full Text Available Inflammatory bowel disease (IBD is a chronically relapsing inflammatory disorder of the gastrointestinal tract. Most IBD treatments are unsatisfactory; therefore, various dietary supplements have emerged as promising interventions. Laminaria japonica (LJ is an edible seaweed used to regulate digestive symptoms. Probiotics have been reported to improve digestive problems and their simultaneous administration with seaweeds has been shown to produce synergistic therapeutic effects. Here, we investigated the effect of LJ combination with probiotics on dextran sodium sulfate-induced colitis model in mice. Aqueous LJ extracts (LJE at doses from 100 to 300 mg/kg and probiotics at a dose of 300 mg/kg were orally administered for 7 days. Body weight, colon length, histological score, macroscopic damage, and the levels of cytokines IFN-γ, IL-1β, IL-6, IL-10, IL-12 (P40, IL-12 (P70, IL-17, and TNF-α were assessed. LJE alone caused a significant improvement of colitis signs such as colon length, histological score, and IL-1β and IL-6 production. LJE and probiotics demonstrated a synergistic effect by the histological score and levels of IL-1β, IL-6, and IL-12 (P40 but not IFN-γ, IL-10, and IL-12 (P70. In conclusion, LJE was effective in inducing protection against colitis in mice and acted synergistically with probiotics.

  19. Crohn's colitis and idiopathic thrombocytopenic purpura

    OpenAIRE

    Boyne, M.; Dye, K.

    2000-01-01

    A 17 year old girl with active Crohn's colitis developed idiopathic thrombocytopenic purpura that was managed with intravenous immune globulins and cyclosporin A. The possible association between Crohn's disease and immune thrombocytopenia is explored.


Keywords: Crohn's disease; colitis; thrombocytopenia

  20. Microscopic colitis : an unfamiliar but treatable disease

    NARCIS (Netherlands)

    van der Wouden, E. J.; Karrenbeld, A.; Kleibeuker, J. H.; Dijkstra, G.

    2009-01-01

    Chronic diarrhoea is a frequent complaint in clinical practice. Microscopic colitis is the cause of this symptom in 10% of these cases and the prevalence is rising. To exclude microscopic colitis a colonoscopy with multiple biopsies of different regions of the colon is mandatory. A sigmoidoscopy alo

  1. (--Pentazocine induces visceral chemical antinociception, but not thermal, mechanical, or somatic chemical antinociception, in μ-opioid receptor knockout mice

    Directory of Open Access Journals (Sweden)

    Satoh Masamichi

    2011-04-01

    Full Text Available Abstract Background (--Pentazocine has been hypothesized to induce analgesia via the κ-opioid (KOP receptor, although the involvement of other opioid receptor subtypes in the effects of pentazocine remains unknown. In this study, we investigated the role of the μ-opioid (MOP receptor in thermal, mechanical, and chemical antinociception induced by (--pentazocine using MOP receptor knockout (MOP-KO mice. Results (--Pentazocine-induced thermal antinociception, assessed by the hot-plate and tail-flick tests, was significantly reduced in heterozygous and abolished in homozygous MOP-KO mice compared with wildtype mice. The results obtained from the (--pentazocine-induced mechanical and somatic chemical antinociception experiments, which used the hind-paw pressure and formalin tests, were similar to the results obtained from the thermal antinociception experiments in these mice. However, (--pentazocine retained its ability to induce significant visceral chemical antinociception, assessed by the writhing test, in homozygous MOP-KO mice, an effect that was completely blocked by pretreatment with nor-binaltorphimine, a KOP receptor antagonist. In vitro binding and cyclic adenosine monophosphate assays showed that (--pentazocine possessed higher affinity for KOP and MOP receptors than for δ-opioid receptors. Conclusions The present study demonstrated the abolition of the thermal, mechanical, and somatic chemical antinociceptive effects of (--pentazocine and retention of the visceral chemical antinociceptive effects of (--pentazocine in MOP-KO mice. These results suggest that the MOP receptor plays a pivotal role in thermal, mechanical, and somatic chemical antinociception induced by (--pentazocine, whereas the KOP receptor is involved in visceral chemical antinociception induced by (--pentazocine.

  2. Expression of inducible nitric oxide synthase and effects of L-arginine on colonic nitric oxide production and fluid transport in patients with "minimal colitis"

    DEFF Research Database (Denmark)

    Perner, Anders; Andresen, Lars; Normark, Michel;

    2005-01-01

    Some patients with idiopathic, chronic diarrhoea have minimal, non-specific colonic inflammation. As nitric oxide (NO) acts as a secretagogue in the colon, we studied the expression of inducible NO synthase (iNOS) in mucosal biopsies and the effects of NOS stimulation on colonic transfer of fluid...

  3. Kalium kanalers rolle i inflammation i Colitis Ulcerosa

    DEFF Research Database (Denmark)

    Hansen, Lars Koch

    2011-01-01

    Gennemgang af T-cellers kalium kanaler og deres mulige rolle i Colitis Ulcerosa. Artiklen skrevet til Den danske Colitis-Crohn Forenings Medlemsblad.......Gennemgang af T-cellers kalium kanaler og deres mulige rolle i Colitis Ulcerosa. Artiklen skrevet til Den danske Colitis-Crohn Forenings Medlemsblad....

  4. Chemically induced skin carcinogenesis: Updates in experimental models (Review).

    Science.gov (United States)

    Neagu, Monica; Caruntu, Constantin; Constantin, Carolina; Boda, Daniel; Zurac, Sabina; Spandidos, Demetrios A; Tsatsakis, Aristidis M

    2016-05-01

    Skin cancer is one of the most common malignancies affecting humans worldwide, and its incidence is rapidly increasing. The study of skin carcinogenesis is of major interest for both scientific research and clinical practice and the use of in vivo systems may facilitate the investigation of early alterations in the skin and of the mechanisms involved, and may also lead to the development of novel therapeutic strategies for skin cancer. This review outlines several aspects regarding the skin toxicity testing domain in mouse models of chemically induced skin carcinogenesis. There are important strain differences in view of the histological type, development and clinical evolution of the skin tumor, differences reported decades ago and confirmed by our hands‑on experience. Using mouse models in preclinical testing is important due to the fact that, at the molecular level, common mechanisms with human cutaneous tumorigenesis are depicted. These animal models resemble human skin cancer development, in that genetic changes caused by carcinogens and pro‑inflammatory cytokines, and simultaneous inflammation sustained by pro‑inflammatory cytokines and chemokines favor tumor progression. Drugs and environmental conditions can be tested using these animal models. keeping in mind the differences between human and rodent skin physiology. PMID:26986013

  5. Increased Neuronal Hypoxic Tolerance Induced by Repetitive Chemical Hypoxia

    Institute of Scientific and Technical Information of China (English)

    李红戈; 刘昌勤; 孙圣刚

    2002-01-01

    Summary: To investigate the effects of time interval and cumulative dosage of repetitive mild cellular hypoxia on shape of neurodegeneration and neuroprotection in mice, population spike amplitude (PSA) was measured during hypoxia and posthypoxic recovery in hippocampal slices from untreated control and mice pretreated in vivo with a single or repeatedly intraperitoneal injection of 3-nitropropi onate (3-NP). Posthypoxic recovery of PSA was dose-dependent in single pretreated slices, with maximal recovery on pretreatment attained with 20 mg/kg 3-NP (82±32%, P< 0. 01). Upon 5 and 9 treatments with 20 mg/kg 3-NP (dosage interval 3 days), PSA recovered to (38±9) % with the difference being not significant vs control group and (72±45) % with the difference being signif icant (P< 0. 05 to control, P<0.05 to 5 treatments), respectively. In contrast, with 2 days time interval, recovery after 5 and 9 treatments was (30±25) % and (16±14) %, respectively (without significant difference from control). Continued neuroprotection was also observed upon increase of dosage interval to 4 and 5 days. It was suggested that repetitive chemical hypoxia is a model for neu rodegenerative disease and continued neuroprotection depending on time interval between repetitive hypoxic episodes rather than cumulative dosage. At appropriate time intervals increased neuronal hy-poxic tolerance could be induced with number of hypoxic episodes.

  6. Doenjang prepared with mixed starter cultures attenuates azoxymethane and dextran sulfate sodium-induced colitis-associated colon carcinogenesis in mice

    Directory of Open Access Journals (Sweden)

    Ji-Kang Jeong

    2014-01-01

    Full Text Available Backgrounds: Doenjang is traditional Korean fermented soybean paste and widely known for its various health benefits including anticancer effect. In this study, we manufactured doenjang with the grain-type meju using probiotic mixed starter cultures of Aspegillus oryzae, Bacillus subtilis-SKm, and Lactococcus lactis-GAm to improve the qualities and beneficial properties of doenjang. Materials and Methods: The inhibitory effects of the doenjang prepared with the grain-type meju using mixed starter cultures were investigated in azoxymethane (AOM and dextran sulfate sodium (DSS-induced colon carcinogenesis mice model. AOM and DSS colon carcinogenesis was induced in female C57BL/6 mice, and doenjang was orally administered for 4 weeks. Body weight, colon length, and colon weight of mice were determined, and colonic tissues were histologically evaluated. The serum levels of proinflammatory cytokines as well as the expression of inflammation- and apoptosis-related genes in colonic tissue were also analyzed. Results: Administration of the doenjang using probiotic mixed starter cultures ameliorated the symptoms of colon cancer, and reduced the incidence of neoplasia, and reduced the levels of serum proinflammatory cytokines such as interleukin-6, and tumor necrosis factor-α and inducible nitric oxide synthase and cycloooxygenase-2 expression levels in colonic tissue. In addition, it increased Bax and reduced Bcl-2 expression levels and increased p21 and p53 expression in the colonic tissues. Conclusion: These findings indicate that the doenjang attenuated colon carcinogenesis induced by AOM and DSS by ameliorating the symptoms of colon cancer, reducing the occurrence of neoplasia, regulating proinflammatory cytokine levels, and controlling the expressions of inflammation- and apoptosis-related genes in the colonic tissue.

  7. CXCR4 antagonist AMD3100 attenuates colonic damage in mice with experimental colitis

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM:To investigate the effects of the chemokine stromal cell-derived factor-1(CXCL12) receptor(CXCR4) antagonist AMD3100 on colonic inflammation and epithelial barrier in dextran sulfate sodium(DSS)-induced colitis in mice.METHODS:Experimental colitis was induced by administration of 5% DSS for 7 d,and assays performed on intestinal segments from the ileocecal valve to the anus.Colonic morphology was examined by hematoxylin and eosin staining.Colonic cytokines were determined by enzyme-linked immunosorbent ...

  8. Modulation of the intestinal microbiota alters colitis-associated colorectal cancer susceptibility.

    Directory of Open Access Journals (Sweden)

    Joshua M Uronis

    Full Text Available It is well established that the intestinal microbiota plays a key role in the pathogenesis of Crohn's disease (CD and ulcerative colitis (UC collectively referred to as inflammatory bowel disease (IBD. Epidemiological studies have provided strong evidence that IBD patients bear increased risk for the development of colorectal cancer (CRC. However, the impact of the microbiota on the development of colitis-associated cancer (CAC remains largely unknown. In this study, we established a new model of CAC using azoxymethane (AOM-exposed, conventionalized-Il10(-/- mice and have explored the contribution of the host intestinal microbiota and MyD88 signaling to the development of CAC. We show that 8/13 (62% of AOM-Il10(-/- mice developed colon tumors compared to only 3/15 (20% of AOM- wild-type (WT mice. Conventionalized AOM-Il10(-/- mice developed spontaneous colitis and colorectal carcinomas while AOM-WT mice were colitis-free and developed only rare adenomas. Importantly, tumor multiplicity directly correlated with the presence of colitis. Il10(-/- mice mono-associated with the mildly colitogenic bacterium Bacteroides vulgatus displayed significantly reduced colitis and colorectal tumor multiplicity compared to Il10(-/- mice. Germ-free AOM-treated Il10(-/- mice showed normal colon histology and were devoid of tumors. Il10(-/-; Myd88(-/- mice treated with AOM displayed reduced expression of Il12p40 and Tnfalpha mRNA and showed no signs of tumor development. We present the first direct demonstration that manipulation of the intestinal microbiota alters the development of CAC. The TLR/MyD88 pathway is essential for microbiota-induced development of CAC. Unlike findings obtained using the AOM/DSS model, we demonstrate that the severity of chronic colitis directly correlates to colorectal tumor development and that bacterial-induced inflammation drives progression from adenoma to invasive carcinoma.

  9. Colitis ulserosaa sairastavan potilaan ohjaus

    OpenAIRE

    Södervik, Satu; Liimatainen, Erja

    2011-01-01

    Opinnäytetyön toimeksiantajana olivat Keski-Suomen Sairaanhoitopiirin sisätautiosasto 11 ja sisätau-tien poliklinikka. Opinnäytetyön tarkoituksena oli selvittää, miten Colitis ulcerosa potilaat kokevat saa-mansa ohjauksen riittävyyden ja ajankohdan, sekä mitä asioita hoitajat ohjaavat potilaille ja millä taval-la hoitajat haluavat kehittää jo annettavaa ohjausta. Opinnäytetyön tavoitteena oli, että tutkimustuloksia voidaan hyödyntää sisätautien osastoilla ja polikli-nikoilla annettavassa C...

  10. Colitis after polytrauma: Case report

    Directory of Open Access Journals (Sweden)

    William E. Carter, MD, MPH

    2014-07-01

    Full Text Available Across the medical literature, delayed diagnosis and treatment leads to more costly and worse outcomes. Rehabilitation patients, especially those with polytrauma, often have a complex mixture of medical, social, and psychological health problems that can impair effective diagnosis and treatment. The case presentation describes the procession toward the diagnosis of ulcerative colitis in a preinjury asymptomatic male, suggesting a potential mechanism for its emergence and describing the effect of delayed diagnosis on the efficiency of rehabilitative care. As such, the differential diagnosis for early posttraumatic diarrhea should remain broad, particularly if unexplained or ineffectively controlled.

  11. Phylotype-level 16S rRNA analysis reveals new bacterial indicators of health state in acute murine colitis

    OpenAIRE

    Berry, David; Schwab, Clarissa; Milinovich, Gabriel; Reichert, Jochen; Ben Mahfoudh, Karim; Decker, Thomas; Engel, Marion; Hai, Brigitte; Hainzl, Eva; Heider, Susanne; Kenner, Lukas; Müller, Mathias; Rauch, Isabella; Strobl, Birgit; Wagner, Michael

    2012-01-01

    Human inflammatory bowel disease and experimental colitis models in mice are associated with shifts in intestinal microbiota composition, but it is unclear at what taxonomic/phylogenetic level such microbiota dynamics can be indicative for health or disease. Here, we report that dextran sodium sulfate (DSS)-induced colitis is accompanied by major shifts in the composition and function of the intestinal microbiota of STAT1−/− and wild-type mice, as determined by 454 pyrosequencing of bacterial...

  12. Preventive use of Lactobacillus plantarum LS/07 and inulin to relieve symptoms of acute colitis.

    Science.gov (United States)

    Hijová, Emília; Šoltésová, Alena; Salaj, Rastislav; Kuzma, Jozef; Strojný, Ladislav; Bomba, Alojz; Gregová, Kristína

    2015-01-01

    The aim of presented study was to investigate the influence of Lactobacillus plantarum LS/07 and inulin on the activity of β-glucuronidase enzyme, and counts of coliform and lactobacilli in fresh caecal digesta, cytokine levels (IL-6, IL-8), and trancription nuclear factor kappa beta (NFκB) activities in colon tissue and blood samples of rats with dextran sulphate sodium (DSS) induced acute colitis. The rats were randomly divided into four groups - CG, AC, AC+PRE and AC+PRO. Colitis was induced using of 5% DSS in drinking water for 7d. DSS application increased activity of β-glucuronidase (P LS/07 decreased β-glucuronidase activity (P LS/07 and inulin suppressed expression observed markers, which play an important role in the inflammatory process, which predisposes their use in prevention or treatment of acute colitis.

  13. Jumihaidokuto effectively inhibits colon inflammation and apoptosis in mice with acute colitis.

    Science.gov (United States)

    Sreedhar, Remya; Arumugam, Somasundaram; Karuppagounder, Vengadeshprabhu; Thandavarayan, Rajarajan A; Giridharan, Vijayasree V; Pitchaimani, Vigneshwaran; Afrin, Mst Rejina; Harima, Meilei; Nakamura, Takashi; Nakamura, Masahiko; Suzuki, Kenji; Watanabe, Kenichi

    2015-12-01

    Jumihaidokuto, a Japanese kampo medicine, is prescribed in Japan for its anti-inflammatory activity. Here we have examined its beneficial effects against acute colitis induced by dextran sulfate sodium (DSS) in mice. We have used C57BL/6 female mice, divided into two groups and received 3% DSS in drinking water during the experimental period (8days). Treatment group mice received 1g/kg/day dose of Jumihaidokuto orally whereas DSS control group received equal volume of distilled water. Normal control group mice received plain drinking water. Jumihaidokuto treatment attenuated the colitis symptoms along with suppression of various inflammatory marker proteins such as IL-1β, IL-2Rα, IL-4, CTGF and RAGE. It has also down-regulated the oxidative stress and apoptotic signaling in the colons of mice with colitis. The present study has confirmed the beneficial effects of Jumihaidokuto on DSS induced acute colitis in mice and suggests that it can be a potential agent for the treatment of colitis.

  14. Cytomegalovirus-colitis hos immunkompetent ung mand

    DEFF Research Database (Denmark)

    Rasmussen, Eva; Grønbaek, Karin; Linnemann, Dorte

    2009-01-01

    haematochezia remained present after six months. Development of IBD subsequent to CMV colitis has previously been described, and is now suspected in our patient. CMV colitis is a rare but possible differential diagnosis in immunocompetent patients with fever, elevated liver enzymes and bloody stools......A healthy young man was hospitalized due to fever, malaise and bloody stools for three weeks. The patient had a primary CMV infection based on biochemical, serological and ultrasonic results, and a colonoscopy was consistent with left-sided CMV colitis. He recovered spontaneously, though...

  15. Left Ventricular Thrombosis in Ulcerative Colitis

    Directory of Open Access Journals (Sweden)

    Tarek Saleh

    2010-07-01

    Full Text Available Left ventricular thrombi usually occur in the setting of an acute myocardial infarction, left ventricular aneurysm, or dilated cardiomyopathy. In the absence of ventricular wall motion abnormalities, they are rare. This report describes a patient with ulcerative colitis in whom two-dimensional echocardiography revealed a left intraventricular mass. Thrombosis in ulcerative colitis is a serious condition and can occur in a very young population. This case also shows that left ventricular thrombi can occur in the active setting of ulcerative colitis.

  16. The Synergic Anti-inflammatory Impact of Gleditsia sinensis Lam. and Lactobacillus brevis KY21 on Intestinal Epithelial Cells in a DSS-induced Colitis Model.

    Science.gov (United States)

    Kim, Younghoon; Koh, Ji Hoon; Ahn, Young Jun; Oh, Sejong; Kim, Sea Hun

    2015-01-01

    We investigated the synergic anti-inflammatory activity of Gleditsia sinensis Lam. (GS) extract and Lactobacillus brevis KY21 both in vitro and in vivo. Western blot analysis and immunostaining showed that AKT phosphorylation that increased by the exposure of LPS were significantly decreased by the presence of either GS extract or L. brevis KY21. In addition, p65 intracellular transport was critically inhibited by GS extract and L. brevis KY21. We further studied these effects using an in vivo dextran sulfate sodium (DSS)-induced mouse model. Body weight, food intake, and clinical scores were dramatically decreased after treatment with DSS, whereas these effects were palliated by the addition of GS extract and L. brevis KY21. Importantly, transcription of genes encoding pro-inflammatory cytokines including IL-1β, TNF-α, and IFN-γ in mesenteric lymph nodes (MLN) and the spleen were increased by DSS treatment, whereas they were inhibited by the presence of GS extract and L. brevis KY21.

  17. Fermented Pueraria Lobata extract ameliorates dextran sulfate sodium-induced colitis by reducing pro-inflammatory cytokines and recovering intestinal barrier function

    Science.gov (United States)

    Choi, Seungho; Woo, Jong-Kyu; Jang, Yeong-Su; Kang, Ju-Hee; Jang, Jung-Eun; Yi, Tae-Hoo; Park, Sang-Yong; Kim, Sun-Yeou; Yoon, Yeo-Sung

    2016-01-01

    Inflammatory bowel disease is a chronic inflammatory disorder occurring in the gastrointestinal track. However, the efficacy of current therapeutic strategies has been limited and accompanied by side effects. In order to eliminate the limitations, herbal medicines have recently been developed for treatment of IBD. Peuraria Lobata (Peuraria L.) is one of the traditional herbal medicines that have anti-inflammatory effects. Bioavailability of Peuraria L., which is rich in isoflavones, is lower than that of their fermented forms. In this study, we generated fermented Peuraria L. extracts (fPue) and investigated the role of fPue in inflammation and intestinal barrier function in vitro and in vivo. As the mice or intestinal epithelial cells were treated with DSS/fPue, mRNA expression of pro-inflammatory cytokines was reduced and the architecture and expression of tight junction proteins were recovered, compared to the DSS-treated group. In summary, fPue treatment resulted in amelioration of DSS-induced inflammation in the colon, and the disrupted intestinal barrier was recovered as the expression and architecture of tight junction proteins were retrieved. These results suggest that use of fPue could be a new therapeutic strategy for treatment of IBD. PMID:27729931

  18. [Simultaneous occurrence of lymphocytic gastritis and lymphocytic colitis with transition to collagenous colitis].

    Science.gov (United States)

    Christ, A D; Meier, R; Bauerfeind, P; Wegmann, W; Gyr, K

    1993-07-31

    Lymphocytic gastritis and lymphocytic colitis are two rare disorders of unknown etiology, only diagnosable by histology. Simultaneous occurrence of lymphocytic colitis and lymphocytic gastritis has not been described up to now. A 69-year-old female patient was examined because of crampy abdominal pain and watery diarrhea. Laboratory tests did not reveal an etiology and in colonoscopy the colon and terminal ileum were normal. Histology disclosed lymphocytic colitis. Esophagogastroduodenoscopy showed erosive bulbitis. Biopsies of the stomach revealed lymphocytic gastritis. A second colonoscopy one year later showed the development of collagenous colitis. PMID:8367708

  19. Chemical -induced apoptotic cell death in tomato cells : involvement of caspase-like proteases

    NARCIS (Netherlands)

    Jong, de A.J.; Hoeberichts, F.A.; Yakimova, E.T.; Maximova, E.; Woltering, E.J.

    2000-01-01

    A new system to study programmed cell death in plants is described. Tomato (Lycopersicon esculentum Mill.) suspension cells were induced to undergo programmed cell death by treatment with known inducers of apoptosis in mammalian cells. This chemical-induced cell death was accompanied by the characte

  20. Giardia duodenalis infection reduces granulocyte infiltration in an in vivo model of bacterial toxin-induced colitis and attenuates inflammation in human intestinal tissue.

    Directory of Open Access Journals (Sweden)

    James A Cotton

    Full Text Available Giardia duodenalis (syn. G. intestinalis, G. lamblia is a predominant cause of waterborne diarrheal disease that may lead to post-infectious functional gastrointestinal disorders. Although Giardia-infected individuals could carry as much as 106 trophozoites per centimetre of gut, their intestinal mucosa is devoid of overt signs of inflammation. Recent studies have shown that in endemic countries where bacterial infectious diseases are common, Giardia infections can protect against the development of diarrheal disease and fever. Conversely, separate observations have indicated Giardia infections may enhance the severity of diarrheal disease from a co-infecting pathogen. Polymorphonuclear leukocytes or neutrophils (PMNs are granulocytic, innate immune cells characteristic of acute intestinal inflammatory responses against bacterial pathogens that contribute to the development of diarrheal disease following recruitment into intestinal tissues. Giardia cathepsin B cysteine proteases have been shown to attenuate PMN chemotaxis towards IL-8/CXCL8, suggesting Giardia targets PMN accumulation. However, the ability of Giardia infections to attenuate PMN accumulation in vivo and how in turn this effect may alter the host inflammatory response in the intestine has yet to be demonstrated. Herein, we report that Giardia infection attenuates granulocyte tissue infiltration induced by intra-rectal instillation of Clostridium difficile toxin A and B in an isolate-dependent manner. This attenuation of granulocyte infiltration into colonic tissues paralled decreased expression of several cytokines associated with the recruitment of PMNs. Giardia trophozoite isolates that attenuated granulocyte infiltration in vivo also decreased protein expression of cytokines released from inflamed mucosal biopsy tissues collected from patients with active Crohn's disease, including several cytokines associated with PMN recruitment. These results demonstrate for the first time

  1. Chemically and temperature-induced phase transformations of metal vanadates

    Science.gov (United States)

    Patridge, Christopher James

    Metal vanadates contain a diverse family of compounds due to the facile accessibility of different vanadium oxidation states and local coordination environments. Though these systems present a number of applications in catalysis and electronics, there may exist untapped physical phenomena that only reveal themselves when scaling these materials to nanoscale dimensions. Finite-size effects result from a number of factors including surface energy structural instabilities, nanostructure "self-purification," and physical constraints on mechanistic or conductive pathways. The MxV2O 5 bronze materials possess non-stoichiometry and this interesting property has hindered synthetic techniques to procure perfect crystalline material which is needed to expose the true physical properties. Through hydrothermal synthesis methods, pseudo one---dimensional nanostructures of Mx V2O5 display fascinating new properties and may be model systems for studying fundamentals associated with correlated electron dynamics in solid-state physics. Electron microscopy and powder X-ray diffraction reveal the near-perfect crystalline nanostructures. X-ray absorption spectroscopy studies show strong evidence for the localization of electron density and long-range crystal structure alignment of the nanowires. Single-nanowire electron transport measurements for the beta'-CuxV2O5 and the delta-KxV2O5 data shows novel temperature-induced reversible metal---insulator transition (MIT) near room temperature. The unprecedented magnitude (˜105) and discontinuous nature of the MIT suggests a mechanism closely associated with correlated electron motion. Additionally, the MIT can be induced by voltage ramping. The simultaneous temperature/voltage studies of single-nanowire transport support the existence of a critical threshold to overcome in order to facilitate instability in the insulating phase and transition to a metallic phase for the delta-KxV2O5 bronze. The MIT transition magnitudes of several

  2. Future targets for immune therapy in colitis?

    DEFF Research Database (Denmark)

    Kristensen, Nanna Ny; Claesson, M H

    2008-01-01

    Crohn's disease and Ulcerative Colitis, collectively termed inflammatory bowel disease (IBD), are chronic inflammatory disorders of the bowel. It is generally accepted that the pathology associated with IBD is characterized by a hyper-reactive immune response in the gut wall directed against...... cells to the inflamed bowel of IBD patients, making the chemokine/receptor system appealing as new therapeutic targets to sustain remission in these patients. In the severe combined immunodeficiency transfer model of colitis, which histopathologically resembles human IBD, low numbers of CD4+CD25- T...... cells from congenic normal mice are transplanted into immune deficient mice, which in turn develop a chronic lethal colitis within 1-2 months. By simultaneous transplantation of CD4+CD25+ regulatory T cells (Tregs) it is possible to hinder development of colitis. Thus the model is well suited...

  3. A Limited Role of p53 on the Ability of a Hexane Fraction of American Ginseng to Suppress Mouse Colitis

    Directory of Open Access Journals (Sweden)

    Deepak Poudyal

    2012-01-01

    Full Text Available Ulcerative colitis (UC is debilitating and carries a high colon cancer risk. Apoptosis of inflammatory cells is a key mechanism regulating UC. We have recently shown that American ginseng (AG, and to a greater extent, a Hexane fraction of AG (HAG can cause apoptosis and suppress mouse colitis through a p53-mediated mechanism. Here, we tested the hypothesis that HAG suppresses colitis through a p53 mechanism. We found only a limited impact of p53 in the ability of HAG to induce inflammatory cell apoptosis and suppress mouse colitis in vitro and in vivo. Finally, we asked whether HAG could cause cell cycle arrest of HCT116 colon cancer cells in vitro. Interestingly, HAG caused a G1 arrest of such cells independent of p53 status. Findings are significant because HAG suppresses colitis and associated colon cancer, and mutation in p53 is observed in most colitis-driven colon cancers. Therefore, HAG might be very effective in targeting the inflammatory cells and cancer cells since it induces apoptosis of inflammatory cells and cell cycle arrest in both p53−/− and WT p53 colon cancer cells.

  4. Effect of iron supplementation on oxidative stress and intestinal inflammation in rats with acute colitis.

    Science.gov (United States)

    Aghdassi, E; Carrier, J; Cullen, J; Tischler, M; Allard, J P

    2001-05-01

    In this study, we investigated the effect of intraperitoneal iron dextran (100 mg/100 g body weight) on oxidative stress and intestinal inflammation in rats with acute colitis induced by 5% dextran sulfate sodium. In both colitis and healthy animals, disease activity index, crypt and inflammatory scores, colon length, plasma and colonic lipid peroxides, and plasma vitamins E, C, and retinol were assessed. The results showed that iron-supplemented groups had moderate iron deposition in the colonic submucosa and lamina propria. In the colitis group supplemented with iron, colon length was significantly shorter; disease activity index, crypt, and inflammatory scores and colonic lipid peroxides were significantly higher; and plasma alpha-tocopherol was significantly lower compared to the colitis group without iron supplementation. There was no intestinal inflammation and no significant increase in colonic lipid peroxides in healthy rats supplemented with iron. In conclusion, iron injection resulted in an increased oxidative stress and intestinal inflammation in rats with colitis but not in healthy rats. PMID:11341654

  5. Platelet-Derived CCL5 Regulates CXC Chemokine Formation and Neutrophil Recruitment in Acute Experimental Colitis.

    Science.gov (United States)

    Yu, Changhui; Zhang, Songen; Wang, Yongzhi; Zhang, Su; Luo, Lingtao; Thorlacius, Henrik

    2016-02-01

    Accumulating data suggest that platelets not only regulate thrombosis and haemostasis but also inflammatory processes. Platelets contain numerous potent pro-inflammatory compounds, including the chemokines CCL5 and CXCL4, although their role in acute colitis remains elusive. The aim of this study is to examine the role of platelets and platelet-derived chemokines in acute colitis. Acute colitis is induced in female Balb/c mice by administration of 5% dextran sodium sulfate (DSS) for 5 days. Animals receive a platelet-depleting, anti-CCL5, anti-CXCL4, or a control antibody prior to DSS challenge. Colonic tissue is collected for quantification of myeloperoxidase (MPO) activity, CXCL5, CXCL2, interleukin-6 (IL-6), and CCL5 levels as well as morphological analyses. Platelet depletion reduce tissue damage and clinical disease activity index in DSS-exposed animals. Platelet depletion not only reduces levels of CXCL2 and CXCL5 but also levels of CCL5 in the inflamed colon. Immunoneutralization of CCL5 but not CXCL4 reduces tissue damage, CXC chemokine expression, and neutrophil recruitment in DSS-treated animals. These findings show that platelets play a key role in acute colitis by regulating CXC chemokine generation, neutrophil infiltration, and tissue damage in the colon. Moreover, our results suggest that platelet-derived CCL5 is an important link between platelet activation and neutrophil recruitment in acute colitis.

  6. Abnormal cannabidiol attenuates experimental colitis in mice, promotes wound healing and inhibits neutrophil recruitment

    OpenAIRE

    Regina M Krohn; Parsons, Sean A.; Fichna, Jakub; Patel, Kamala D.; Yates, Robin M; Keith A Sharkey; Storr, Martin A

    2016-01-01

    Background Non-psychotropic atypical cannabinoids have therapeutic potential in a variety of inflammatory conditions including those of the gastrointestinal tract. Here we examined the effects of the atypical cannabinoid abnormal cannabidiol (Abn-CBD) on wound healing, inflammatory cell recruitment and colitis in mice. Methods Colitis was induced in CD1 mice by a single intrarectal administration of trinitrobenzene sulfonic acid (TNBS, 4 mg/100 μl in 30 % ethanol) and Abn-CBD and/or the antag...

  7. Effect of Arctium lappa L.in the dextran sulfate sodium colitis mouse model

    Institute of Scientific and Technical Information of China (English)

    Tzou-Chi; Huang; Shinn-Shyong; Tsai

    2010-01-01

    AIM:To analyze the possible protective role of Arctium lappa L.(AL)in a murine model of ulcerative colitis(UC).METHODS:BALB/c mice were administered 100 mg/kg AL powder orally each day.After 7 d,colitis was induced by administration of dextran sulfate sodium(DSS)(5% W/V)in drinking water for a further 8 consecutive days.Diarrhea and bloody stools as well as colonic histology were observed.The level of interleukin-6(IL-6)and tu-mor necrosis factor-α(TNF-α)in colonic sections were detected by immunohistochemi...

  8. Intestinal microbiota and ulcerative colitis.

    Science.gov (United States)

    Ohkusa, Toshifumi; Koido, Shigeo

    2015-11-01

    There is a close relationship between the human host and the intestinal microbiota, which is an assortment of microorganisms, protecting the intestine against colonization by exogenous pathogens. Moreover, the intestinal microbiota play a critical role in providing nutrition and the modulation of host immune homeostasis. Recent reports indicate that some strains of intestinal bacteria are responsible for intestinal ulceration and chronic inflammation in inflammatory bowel diseases (IBD) such as ulcerative colitis (UC) and Crohn's disease (CD). Understanding the interaction of the intestinal microbiota with pathogens and the human host might provide new strategies treating patients with IBD. This review focuses on the important role that the intestinal microbiota plays in maintaining innate immunity in the pathogenesis and etiology of UC and discusses new antibiotic therapies targeting the intestinal microbiota.

  9. Protein tyrosine phosphatase 1B deficiency ameliorates murine experimental colitis via the expansion of myeloid-derived suppressor cells.

    Directory of Open Access Journals (Sweden)

    Jing Zhang

    Full Text Available Protein tyrosine phosphatase 1B (PTP1B is a key molecule in modulating low-degree inflammatory conditions such as diabetes. The role of PTP1B in other chronic inflammations, however, remains unknown. Here, we report that PTP1B deficiency ameliorates Dextran Sulfate Sodium (DSS-induced murine experimental colitis via expanding CD11b(+Gr-1(+ myeloid-derived suppressor cells (MDSCs. Employing DSS-induced murine experimental colitis as inflammatory animal model, we found that, compared with wild-type littermates, PTP1B-null mice demonstrated greater resistance to DSS-induced colitis, as reflected by slower weight-loss, greater survival rates and decreased PMN and macrophage infiltration into the colon. The evidence collectively also demonstrated that the resistance of PTP1B-null mice to DSS-induced colitis is based on the expansion of MDSCs. First, PTP1B-null mice exhibited a greater frequency of MDSCs in the bone marrow (BM, peripheral blood and spleen when compared with wild-type littermates. Second, PTP1B levels in BM leukocytes were significantly decreased after cells were induced into MDSCs by IL-6 and GM-CSF, and the MDSC induction occurred more rapidly in PTP1B-null mice than in wild-type littermates, suggesting PTP1B as a negative regulator of MDSCs. Third, the adoptive transfer of MDSCs into mice with DSS-colitis significantly attenuated colitis, which accompanies with a decreased serum IL-17 level. Finally, PTP1B deficiency increased the frequency of MDSCs from BM cells likely through enhancing the activities of signal transducer and activator of transcription 3 (STAT3 and Janus kinase 2 (JAK2. In conclusion, our study provides the first evidences that PTP1B deficiency ameliorates murine experimental colitis via expanding MDSCs.

  10. Oral Bifidobacterium longum expressing alpha-melanocyte-stimulating hormone to fight experimental colitis.

    Science.gov (United States)

    Wei, Pijin; Yang, Yan; Liu, Zhaobing; Huang, Junli; Gong, Yahui; Sun, Hanxiao

    2016-07-01

    The oral delivery of peptides is a highly attractive treatment approach. However, the harsh environment of the gastrointestinal tract limits its application. Here, we utilize Bifidobacterium as a delivery system to orally deliver a potent anti-inflammatory but short duration peptide alpha-melanocyte-stimulating hormone (α-MSH) against experimental colitis. The aim of our study was to facilitate the efficient oral delivery of α-MSH. We designed a vector of pBDMSH and used it to construct a Bifidobacterium longum expressing α-MSH. We then determined the bioactivity of recombinant Bifidobacterium in lipopolysaccharide-induced inflammatory models of HT-29 cells. Finally, we used Bifidobacterium expressing α-MSH against dextran sulfate sodium (DSS)-induced ulcerative colitis mice. Results based on the myeloperoxidase activity, the levels of inflammatory cytokines TNF-α, IL-1β, IL-6, and IL-10 and the histological injury of colon tissue reveal recombinant Bifidobacterium was efficient in attenuating DSS-induced ulcerative colitis, suggesting an alternative way to use Bifidobacterium as a delivery system to deliver α-MSH for DSS-induced ulcerative colitis therapy. PMID:26673899

  11. Gene expression profiling identifies mechanisms of protection to recurrent trinitrobenzene sulfonic acid colitis mediated by probiotics

    NARCIS (Netherlands)

    Mariman, R.; Kremer, S.H.A.; Erk, M. van; Lagerweij, T.; Koning, F.; Nagelkerken, L.

    2012-01-01

    Background: Host-microbiota interactions in the intestinal mucosa play a major role in intestinal immune homeostasis and control the threshold of local inflammation. The aim of this study was to evaluate the efficacy of probiotics in the recurrent trinitrobenzene sulfonic acid (TNBS)-induced colitis

  12. Ciprofloxacin and probiotic Escherichia coli Nissle add-on treatment in active ulcerative colitis

    DEFF Research Database (Denmark)

    Petersen, Andreas Munk; Mirsepasi, Hengameh; Halkjær, Sofie Ingdam;

    2014-01-01

    BACKGROUND AND AIM: Ulcerative colitis (UC) is a chronic inflammatory bowel disease. The probiotic bacterium Escherichia coli Nissle 1917 (EcN) has been used to maintain and induce clinical remission in UC. Our aim was to test the effect of Ciprofloxacin and/or orally administered EcN as add-on to...

  13. Dietary heme adversely affects experimental colitis in rats, despite heat-shock protein induction

    NARCIS (Netherlands)

    Schepens, Marloes A. A.; Vink, Carolien; Schonewille, Arjan J.; Dijkstra, Gerard; van der Meer, Roelof; Bovee-Oudenhoven, Ingeborg M. J.

    2011-01-01

    Objective: Research on dietary modulation of inflammatory bowel disease is in its infancy. Dietary heme, mimicking red meat, is cytotoxic to colonic epithelium and thus may aggravate colitis. Alternatively, heme-induced colonic stress might also result in potential protective heat-shock proteins (HS

  14. Consumption of probiotics increases the effect of regulatory T cells in transfer colitis

    DEFF Research Database (Denmark)

    Petersen, Emil Rathsach; Claesson, Mogens Helweg; Schmidt, Esben Gjerløff Wedebye;

    2012-01-01

    BACKGROUND: Probiotics may alter immune regulation. Recently, we showed that the probiotic bacteria Lactobacillus acidophilus NCFM™ influenced the activity of regulatory T cells (Tregs) in vitro. The aim of the present work was to demonstrate if L. acidophilus NCFM™ also affects the function...... of Tregs in vivo. METHODS: Development of colitis after transfer of CD4+CD25- T cells and protection from colitis by Tregs was studied in immunodeficient SCID mice which were simultaneously tube-fed with L. acidophilus NCFM™ or L. salivarius Ls-33 for 5 weeks. RESULTS: Probiotic-fed SCID mice transplanted...... with low numbers of Tregs in addition to the disease-inducing T cells were completely protected from colitis. This was in contrast to the control group, which showed intermediate levels of inflammation. In addition, feeding with probiotics lowered serum levels of inflammatory cytokines in both colitic mice...

  15. Colonic production of nitric oxide gas in ulcerative colitis, collagenous colitis and uninflamed bowel

    DEFF Research Database (Denmark)

    Perner, Anders; Lassen, Inge Nordgaard; Matzen, Peter;

    2002-01-01

    ulcerative colitis, 10 patients with collagenous colitis and 20 controls with uninflamed mucosa. METHODS: The tip of a Teflon tube was placed in the caecum during colonoscopy. Subsequently, argon was infused at a constant rate for 70-180 min. Argon and NO in gas sampled from the rectum were measured by...

  16. Lansoprazole-associated collagenous colitis: Diffuse mucosal cloudiness mimicking ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Mitsuro Chiba; Takeshi Sugawara; Haruhiko Tozawa; Hidehiko Tsuda; Toru Abe; Takuo Tokairin; Iwao Ono; Eriko Ushiyama

    2009-01-01

    There have only been a few reports on lansoprazoleassociated collagenous colitis. Colonic mucosa of collagenous colitis is known to be endoscopically normal. We present a case of collagenous colitis where the mucosa showed diffuse cloudiness mimicking ulcerative colitis. A 70-year-old woman developed watery diarrhea four to nine times a day. She had interstitial pneumonia at 67 and reflux esophagitis at 70 years. Lansoprazole 30 mg/d had been prescribed for reflux esophagitis for nearly 6 mo. Lansoprazole was withdrawn due to its possible side effect of diarrhea. Colonoscopy disclosed diffuse cloudiness of the mucosa which suggested ulcerative colitis. Consequently sulfasalazine 2 g/d was started. The patient's diarrhea dramatically disappeared on the following day. However, biopsy specimens showed subepithelial collagenous thickening and infiltration of inflammatory cells in the lamina propria, confirming the diagnosis of collagenous colitis. One month after sulfasalazine therapy was initiated, colonoscopic and histological abnormalities resolved completely. Five months later the diarrhea recurred. The findings on colonoscopy and histology were the same as before, confirming a diagnosis of collagenous colitis relapse. We found that the patient had begun to take lansoprazole again 3 mo ahead of the recent diarrhea. Withdrawal of lansoprazole promptly resolved the diarrhea. Endoscopic and histological abnormalities were also completely resolved, similar to the first episode. Retrospectively, the date of commencement of sulfasalazine and discontinuation of lansoprazole in the first episode was found to be the same. We conclude that this patient had lansoprazole-associated collagenous colitis.

  17. Escherichia coli strain Nissle 1917 ameliorates experimental colitis by modulating intestinal permeability, the inflammatory response and clinical signs in a faecal transplantation model.

    Science.gov (United States)

    Souza, Éricka L; Elian, Samir D; Paula, Laís M; Garcia, Cristiana C; Vieira, Angélica T; Teixeira, Mauro M; Arantes, Rosa M; Nicoli, Jacques R; Martins, Flaviano S

    2016-03-01

    Inflammatory bowel diseases (IBDs) are a group of inflammatory conditions of the gut that include ulcerative colitis and Crohn's disease. Probiotics are live micro-organisms that may be used as adjuvant therapy for patients with IBD. The aim of this study was to evaluate the effect of prophylactic ingestion of Escherichia coli strain Nissle 1917 (EcN) in a murine model of colitis. For induction of colitis, mice were given a 3.5% dextran sodium sulfate (DSS) solution for 7 days in drinking water. EcN administration to mice subjected to DSS-induced colitis resulted in significant reduction in clinical and histopathological signs of disease and preservation of intestinal permeability. We observed reduced inflammation, as assessed by reduced levels of neutrophils, eosinophils, chemokines and cytokines. We observed an increase in the number of regulatory T-cells in Peyer's patches. Germ-free mice received faecal content from control or EcN-treated mice and were then subjected to DSS-induced colitis. We observed protection from colitis in animals that were colonized with faecal content from EcN-treated mice. These results suggest that preventative oral administration of EcN or faecal microbiota transplantation with EcN-containing microbiota ameliorates DSS-induced colitis by modifying inflammatory responsiveness to DSS.

  18. Usefulness of colonoscopy in ischemic colitis Utilidad de la colonoscopia en la colitis isquémica

    Directory of Open Access Journals (Sweden)

    M. Lozano Maya

    2010-08-01

    colonoscopia y biopsia, en un periodo de tiempo de cinco años. Se analizaron: edad, sexo, motivo de exploración, factores de riesgo cardiovascular, grado endoscópico de isquemia, cambio en la actitud terapéutica, tratamiento y evolución. Resultados: la edad media de nuestros pacientes fue de 73,6 ± 12,1 años con una incidencia similar en ambos sexos (50,9% mujeres y 49,1% hombres. Los factores de riesgo asociados fueron la hipertensión arterial (61,1%, el tabaco (37,2% y antecedente de accidente cardiovascular previo (52,2%. El motivo más frecuente de realización de colonoscopia fue rectorragia (53,6% seguido de dolor abdominal (30,4%, realizándose de forma urgente en el 65,3% de los casos. La colonoscopia permitió un cambio en la actitud terapéutica en el 50% de los casos, aumentando en la urgente al 65,75%. La mortalidad global fue del 27,67%. La colitis isquémica grave (25% fue más frecuente en varones (64,3%, y cuando la indicación de colonoscopia fue urgente (85,71% y cursó con mortalidad alta (53,57%. En estos se realizó tratamiento quirúrgico en el 57,14% de los casos con una evolución favorable en el 50%, mientras que los pacientes con colitis isquémica leve o moderada tuvieron un pronóstico mejor, con evolución favorable en el 80,95% de los casos y con menor requerimiento de tratamiento quirúrgico (4,76%, p < 0,05. Conclusión: la colitis isquémica es más frecuente en la edad avanzada. La sintomatología más común es la rectorragia y el dolor abdominal. La colonoscopia permite evaluar la gravedad e induce un cambio de actitud según el resultado de la misma. La evidencia de una colitis grave supuso un aumento de la necesidad de cirugía y peor pronóstico.

  19. Plecanatide and dolcanatide, novel guanylate cyclase-C agonists, ameliorate gastrointestinal inflammation in experimental models of murine colitis

    Institute of Scientific and Technical Information of China (English)

    Kunwar; Shailubhai; Vaseem; Palejwala; Krishna; Priya; Arjunan; Sayali; Saykhedkar; Bradley; Nefsky; John; A; Foss; Stephen; Comiskey; Gary; S; Jacob; Scott; E; Plevy

    2015-01-01

    AIM: To evaluate the effect of orally administeredplecanatide or dolcanatide, analogs of uroguanylin, on amelioration of colitis in murine models.METHODS: The cyclic guanosine monophosphate(cG MP) stimulatory potency of plecanatide and dolcanatide was measured using a human colon carcinoma T84 cellbased assay. For animal studies all test agents were formulated in phosphate buffered saline. Sulfasalazine or 5-amino salicylic acid(5-ASA) served as positive controls. Effect of oral treatment with test agents on amelioration of acute colitis induced either by dextran sulfate sodium(DSS) in drinking water or by rectal instillation of trinitrobenzene sulfonic(TNBS) acid, was examined in BALB/c and/or BDF1 mice. Additionally, the effect of orally administered plecanatide on the spontaneous colitis in T-cell receptor alpha knockout(TCRα-/-) mice was also examined. Amelioration of colitis was assessed by monitoring severity of colitis, disease activity index and by histopathology. Frozen colon tissues were used to measure myeloperoxidase activity.RESULTS: Plecanatide and dolcanatide are structurally related analogs of uroguanylin, which is an endogenous ligand of guanylate cyclase-C(GC-C). As expected from the agonists of GC-C, both plecanatide and dolcanatide exhibited potent cG MP-stimulatory activity in T84 cells. Once-daily treatment by oral gavage with either of these analogs(0.05-0.5 mg/kg) ameliorated colitis in both DSS and TNBS-induced models of acute colitis, as assessed by body weight, reduction in colitis severity(P < 0.05) and disease activity index(P < 0.05). Amelioration of colitis by either of the drug candidates was comparable to that achieved by orally administered sulfasalazine or 5-ASA. Plecanatide also effectively ameliorated colitis in TCRα-/- mice, a model of spontaneous colitis. As dolcanatide exhibited higher resistance to proteolysis in simulated gastric and intestinal juices, it was selected for further studies. CONCLUSION: This is the first

  20. Spectroscopic Observation of Chemical Interaction Between Impact-induced Vapor Clouds and the Ambient Atmosphere

    Science.gov (United States)

    Sugita, S.; Heineck, J. T.; Schultz, P. H.

    2000-01-01

    Chemical reactions within impact-induced vapor clouds were observed in laboratory experiments using a spectroscopic method. The results indicate that projectile-derived carbon-rich vapor reacts intensively with atmospheric nitrogen.

  1. Polyphosphate, an active molecule derived from probiotic Lactobacillus brevis, improves the fibrosis in murine colitis.

    Science.gov (United States)

    Kashima, Shin; Fujiya, Mikihiro; Konishi, Hiroaki; Ueno, Nobuhiro; Inaba, Yuhei; Moriichi, Kentaro; Tanabe, Hiroki; Ikuta, Katsuya; Ohtake, Takaaki; Kohgo, Yutaka

    2015-08-01

    Inflammatory bowel disease frequently causes intestinal obstruction because of extensive fibrosis. This study investigated whether polyphosphate (poly P), an active molecule derived from Lactobacillus brevis, could improve the fibrosis in a model of chronic colitis. In this study, dextran sodium sulfate (DSS)-induced chronic colitis models and trinitrobenzene sulfonic acid (TNBS)-induced colitis models were used as models of fibrosis. To clarify the mechanism responsible for the observed effects, Caco-2/brush border epithelial (BBE) and naive T helper lymphocyte (THP)-1 cells were treated with lipopolysaccharide (LPS) to induce inflammation. Non-cancer human colon fibroblast (CCD-18) cells were treated with transforming growth factor beta 1 (TGF-β1) to induce fibrosis. The expression levels of fibrosis- and inflammation-associated molecules were evaluated by both a Western blotting analysis and reverse transcriptase-polymerase chain reaction (RT-PCR). The histologic inflammation and fibrosis were significantly improved in the group administered poly P in both the DSS and TNBS colitis models. The levels of interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) were significantly decreased by poly P treatment. The expression levels of TGF-β1 and collagens in the colitis mice were decreased by poly P. The LPS-induced expressions of IL-1β and TGF-β1 in Caco-2/BBE cells and of TNF-α in THP-1 cells were reduced by poly P treatment. Poly P did not affect the expression of collagens and connective tissue growth factor in the CCD-18 cells. In conclusion, poly P suppresses intestinal inflammation and fibrosis by downregulating the expression of inflammation- and fibrosis-associated molecules in the intestinal epithelium. The administration of poly P is therefore a novel option to treat fibrosis because of chronic intestinal inflammation. PMID:25766132

  2. Chemically-induced Mouse Lung Tumors: Applications to Human Health Assessments

    Science.gov (United States)

    A state-of-the-science workshop on chemically-induced mouse lung tumors was conducted by U.S. Environmental Protection Agency to better understand the mouse lung tumor data’s role in human health assessments. Three environmental chemicals - naphthalene, styrene, and ethylbe...

  3. Chlorine Dioxide Induced Multiple Chemical Sensitivity: MMPI Validity Problems.

    Science.gov (United States)

    Tentoni, Stuart C.

    This paper discusses Minnesota Multiphasic Personality Inventory (MMPI) data obtained from individuals exposed to chlorine dioxide in the workplace who developed Multiple Chemical Sensitivity Syndrome. The paper explores current research on chlorine dioxide exposed persons who were misdiagnosed on the basis of MMPI interpretations. Difficulties…

  4. Mammalian models of chemically induced primary malignancies exploitable for imaging-based preclinical theragnostic research

    OpenAIRE

    Liu, Yewei; YIN Ting; Feng, Yuanbo; Cona, Marlein Miranda; Huang, Gang; Liu, Jianjun; Song, Shaoli; Jiang, Yansheng; Xia, Qian; Swinnen, Johannes V; Bormans, Guy; Himmelreich, Uwe; Oyen, Raymond; Ni, Yicheng

    2015-01-01

    Compared with transplanted tumor models or genetically engineered cancer models, chemically induced primary malignancies in experimental animals can mimic the clinical cancer progress from the early stage on. Cancer caused by chemical carcinogens generally develops through three phases namely initiation, promotion and progression. Based on different mechanisms, chemical carcinogens can be divided into genotoxic and non-genotoxic ones, or complete and incomplete ones, usually with an organ-spe...

  5. Vedolizumab as induction and maintenance therapy for ulcerative colitis

    DEFF Research Database (Denmark)

    Feagan, Brian G; Rutgeerts, Paul; Sands, Bruce E;

    2013-01-01

    Gut-selective blockade of lymphocyte trafficking by vedolizumab may constitute effective treatment for ulcerative colitis.......Gut-selective blockade of lymphocyte trafficking by vedolizumab may constitute effective treatment for ulcerative colitis....

  6. Infliximab and complications after colectomy in patients with ulcerative colitis

    DEFF Research Database (Denmark)

    Bregnbak, David; Mortensen, Christian; Bendtsen, Flemming

    2012-01-01

    Infliximab treatment may increase the risk of subsequent postoperative complications in patients with ulcerative colitis. The main purpose of the present study therefore was to assess postoperative complications in patients who have undergone colectomy for ulcerative colitis with and without...

  7. Antiviral treatment in patients with cytomegalovirus positive ulcerative colitis

    OpenAIRE

    Kadir OZTURK

    2014-01-01

    Cytomegalovirus (CMV) is a common virus in patients with ulcerative colitis receiving immunosuppressive drugs. Many studies suggested that CMV infection is an exacerbating factor in patients with ulcerative colitis. The role of CMV in exacerbations of ulcerative colitis has been discussed. One of studies starting this discussion is an article entitled “CMV positive ulcerative colitis: A single center experience and literature review” by Kopylov et al. However, we think that there are some poi...

  8. Hazard classification of chemicals inducing haemolytic anaemia: An EU regulatory perspective.

    NARCIS (Netherlands)

    Muller, Andre; Jacobsen, Helene; Healy, Edel; McMickan, Sinead; Istace, Fréderique; Blaude, Marie-Noëlle; Howden, Peter; Fleig, Helmut; Schulte, Agnes

    2006-01-01

    Haemolytic anaemia is often induced following prolonged exposure to chemical substances. Currently, under EU Council Directive 67/548/EEC, substances which induce such effects are classified as dangerous and assigned the risk phrase R48 'Danger of serious damage to health by prolonged exposure.' Whi

  9. Interleukin-7 receptor blockade suppresses adaptive and innate inflammatory responses in experimental colitis

    Directory of Open Access Journals (Sweden)

    Willis Cynthia R

    2012-10-01

    Full Text Available Abstract Background Interleukin-7 (IL-7 acts primarily on T cells to promote their differentiation, survival, and homeostasis. Under disease conditions, IL-7 mediates inflammation through several mechanisms and cell types. In humans, IL-7 and its receptor (IL-7R are increased in diseases characterized by inflammation such as atherosclerosis, rheumatoid arthritis, psoriasis, multiple sclerosis, and inflammatory bowel disease. In mice, overexpression of IL-7 results in chronic colitis, and T-cell adoptive transfer studies suggest that memory T cells expressing high amounts of IL-7R drive colitis and are maintained and expanded with IL-7. The studies presented here were undertaken to better understand the contribution of IL-7R in inflammatory bowel disease in which colitis was induced with a bacterial trigger rather than with adoptive transfer. Methods We examined the contribution of IL-7R on inflammation and disease development in two models of experimental colitis: Helicobacter bilis (Hb-induced colitis in immune-sufficient Mdr1a−/− mice and in T- and B-cell-deficient Rag2−/− mice. We used pharmacological blockade of IL-7R to understand the mechanisms involved in IL-7R-mediated inflammatory bowel disease by analyzing immune cell profiles, circulating and colon proteins, and colon gene expression. Results Treatment of mice with an anti-IL-7R antibody was effective in reducing colitis in Hb-infected Mdr1a−/− mice by reducing T-cell numbers as well as T-cell function. Down regulation of the innate immune response was also detected in Hb-infected Mdr1a−/− mice treated with an anti-IL-7R antibody. In Rag2−/− mice where colitis was triggered by Hb-infection, treatment with an anti-IL-7R antibody controlled innate inflammatory responses by reducing macrophage and dendritic cell numbers and their activity. Conclusions Results from our studies showed that inhibition of IL-7R successfully ameliorated inflammation and disease development

  10. Chemical products induce resistance to Xanthomonas perforans in tomato

    Directory of Open Access Journals (Sweden)

    Adriana Terumi Itako

    2015-09-01

    Full Text Available The bacterial spot of tomato, caused by Xanthomonas spp., is a very important disease, especially in the hot and humid periods of the year. The chemical control of the disease has not been very effective for a number of reasons. This study aimed to evaluate, under greenhouse conditions, the efficacy of leaf-spraying chemicals (acibenzolar-S-methyl (ASM (0.025 g.L−1, fluazinam (0.25 g.L−1, pyraclostrobin (0.08 g.L−1, pyraclostrobin + methiran (0.02 g.L−1 + 2.2 g.L−1, copper oxychloride (1.50 g.L−1, mancozeb + copper oxychloride (0.88 g.L−1 + 0.60 g.L−1, and oxytetracycline (0.40 g.L−1 on control of bacterial spot. Tomatoes Santa Clara and Gisele cultivars were pulverized 3 days before inoculation with Xanthomonas perforans. The production of enzymes associated with resistance induction (peroxidase, polyphenol oxidase, phenylalanine ammonia-lyase, β-1,3-glucanase, and protease was quantified from leaf samples collected 24 hours before and 24 hours after chemical spraying and at 1, 2, 4, 6, and 8 days after bacterial inoculation. All products tested controlled bacterial spot, but only ASM, pyraclostrobin, and pyraclostrobin + metiram increased the production of peroxidase in the leaves of the two tomato cultivars, and increased the production of polyphenol oxidase and β-1,3-glucanase in the Santa Clara cultivar.

  11. IL-22 Restrains Tapeworm-Mediated Protection against Experimental Colitis via Regulation of IL-25 Expression.

    Science.gov (United States)

    Reyes, José L; Fernando, Maria R; Lopes, Fernando; Leung, Gabriella; Mancini, Nicole L; Matisz, Chelsea E; Wang, Arthur; McKay, Derek M

    2016-04-01

    Interleukin (IL)-22, an immune cell-derived cytokine whose receptor expression is restricted to non-immune cells (e.g. epithelial cells), can be anti-inflammatory and pro-inflammatory. Mice infected with the tapeworm Hymenolepis diminuta are protected from dinitrobenzene sulphonic acid (DNBS)-induced colitis. Here we assessed expulsion of H. diminuta, the concomitant immune response and the outcome of DNBS-induced colitis in wild-type (WT) and IL-22 deficient mice (IL-22-/-) ± infection. Interleukin-22-/- mice had a mildly impaired ability to expel the worm and this correlated with reduced or delayed induction of TH2 immunity as measured by splenic and mesenteric lymph node production of IL-4, IL-5 and IL-13 and intestinal Muc-2 mRNA and goblet cell hyperplasia; in contrast, IL-25 increased in the small intestine of IL-22-/- mice 8 and 12 days post-infection compared to WT mice. In vitro experiments revealed that H. diminuta directly evoked epithelial production of IL-25 that was inhibited by recombinant IL-22. Also, IL-10 and markers of regulatory T cells were increased in IL-22-/- mice that displayed less DNBS (3 mg, ir. 72h)-induced colitis. Wild-type mice infected with H. diminuta were protected from colitis, as were infected IL-22-/- mice and the latter to a degree that they were almost indistinguishable from control, non-DNBS treated mice. Finally, treatment with anti-IL-25 antibodies exaggerated DNBS-induced colitis in IL-22-/- mice and blocked the anti-colitic effect of infection with H. diminuta. Thus, IL-22 is identified as an endogenous brake on helminth-elicited TH2 immunity, reducing the efficacy of expulsion of H. diminuta and limiting the effectiveness of the anti-colitic events mobilized following infection with H. diminuta in a non-permissive host.

  12. IL-22 Restrains Tapeworm-Mediated Protection against Experimental Colitis via Regulation of IL-25 Expression.

    Directory of Open Access Journals (Sweden)

    José L Reyes

    2016-04-01

    Full Text Available Interleukin (IL-22, an immune cell-derived cytokine whose receptor expression is restricted to non-immune cells (e.g. epithelial cells, can be anti-inflammatory and pro-inflammatory. Mice infected with the tapeworm Hymenolepis diminuta are protected from dinitrobenzene sulphonic acid (DNBS-induced colitis. Here we assessed expulsion of H. diminuta, the concomitant immune response and the outcome of DNBS-induced colitis in wild-type (WT and IL-22 deficient mice (IL-22-/- ± infection. Interleukin-22-/- mice had a mildly impaired ability to expel the worm and this correlated with reduced or delayed induction of TH2 immunity as measured by splenic and mesenteric lymph node production of IL-4, IL-5 and IL-13 and intestinal Muc-2 mRNA and goblet cell hyperplasia; in contrast, IL-25 increased in the small intestine of IL-22-/- mice 8 and 12 days post-infection compared to WT mice. In vitro experiments revealed that H. diminuta directly evoked epithelial production of IL-25 that was inhibited by recombinant IL-22. Also, IL-10 and markers of regulatory T cells were increased in IL-22-/- mice that displayed less DNBS (3 mg, ir. 72h-induced colitis. Wild-type mice infected with H. diminuta were protected from colitis, as were infected IL-22-/- mice and the latter to a degree that they were almost indistinguishable from control, non-DNBS treated mice. Finally, treatment with anti-IL-25 antibodies exaggerated DNBS-induced colitis in IL-22-/- mice and blocked the anti-colitic effect of infection with H. diminuta. Thus, IL-22 is identified as an endogenous brake on helminth-elicited TH2 immunity, reducing the efficacy of expulsion of H. diminuta and limiting the effectiveness of the anti-colitic events mobilized following infection with H. diminuta in a non-permissive host.

  13. Therapeutic effects of four strains of probiotics on experimental colitis in mice

    Institute of Scientific and Technical Information of China (English)

    Lin-Lin Chen; Xue-Hong Wang; Yi Cui; Guang-Hui Lian; Jie Zhang; Chun-Hui Ouyang; Fang-Gen Lu

    2009-01-01

    AIM: To investigate the therapeutic effects of four strains of probiotics ( E. feacalis, L. acidophilus,C. butyricum and B. adolescentis) on dextran sulphate sodium (DSS)-induced experimental colitis in Balb/c mice.METHODS: Eighty Balb/c mice were randomly divided into 8 groups. Weight-loss, fecal character, fecal occult blood and hematochezia were recorded daily. Disease activity index (DAI) scores were also evaluated everyday. Length of colon was measured and histological scores were evaluated on the 13th day. Myeloperoxidase (MPO) activity was detected. Interleukin-1 (IL-1) and IL-4 expression was detected by ELISA and RT-PCR.RESULTS: The four strains of probiotics relieved the inflammatory condition of DSS-induced experimental colitis in mice. Weight loss was slowed down in all probiotics-treated mice. Even weight gain was observed by the end of probiotics treatment. The DAI and histological scores of probiotics-treated mice were lower than those of mice in the control group (1.9 ± 0.2vs 8.6 ± 0.4, P < 0.05 for E. faecalis). The length of colon of probiotics-treated mice was longer than thatof mice in the control group (10.3 ± 0.34 vs 8.65 ± 0.77,P < 0.05 for E. faecalis). The four strains of probiotics decreased the MP activity and the IL-1 expression, but increased the IL-4 expression. E. faecalis had a better effect on DSS-induced experimental colitis in mice than the other three strains.CONCLUSION: The four strains of probiotics have beneficial effects on experimental colitis in mice. E. faecalis has a better effect on DSS-induced experimental colitis in mice than the other three strains. Supplement of probiotics provides a new therapy for UC.

  14. CD4+ T regulatory cells from the colonic lamina propria of normal mice inhibit proliferation of enterobacteria-reactive, disease-inducing Th1-cells from scid mice with colitis

    DEFF Research Database (Denmark)

    Gad, M; Brimnes, J; Claesson, Mogens Helweg

    2003-01-01

    -derived dendritic cells effectively suppress the antibacterial proliferative response of CD4+ T cells from scid mice with colitis. The majority of these LP T-reg cells display a nonactivated phenotype and suppression is independent of antigen exposure, is partly mediated by soluble factor(s) different from IL-10...... and TGF-beta, and is not prevented by the addition of high doses of IL-2 to the assay culture. Functionally and phenotypically the T-reg cells of the present study differ from previously described subsets of T-reg cells. The presence of T cells with a regulatory potential in the normal colonic mucosa...

  15. Collagenous colitis as a possible cause of toxic megacolon.

    LENUS (Irish Health Repository)

    Fitzgerald, S C

    2009-03-01

    Collagenous colitis is a microscopic colitis characterized by normal appearing colonic mucosa on endoscopy. It is regarded as a clinically benign disease which rarely results in serious complications. We report a case of toxic megacolon occurring in a patient with collagenous colitis. This is the first reported case of toxic megacolon occurring in this subset of patients.

  16. Noise-induced multistability in chemical systems: Discrete versus continuum modeling.

    Science.gov (United States)

    Duncan, Andrew; Liao, Shuohao; Vejchodský, Tomáš; Erban, Radek; Grima, Ramon

    2015-04-01

    The noisy dynamics of chemical systems is commonly studied using either the chemical master equation (CME) or the chemical Fokker-Planck equation (CFPE). The latter is a continuum approximation of the discrete CME approach. It has recently been shown that for a particular system, the CFPE captures noise-induced multistability predicted by the CME. This phenomenon involves the CME's marginal probability distribution changing from unimodal to multimodal as the system size decreases below a critical value. We here show that the CFPE does not always capture noise-induced multistability. In particular we find simple chemical systems for which the CME predicts noise-induced multistability, whereas the CFPE predicts monostability for all system sizes.

  17. Noise-induced multistability in chemical systems: Discrete versus continuum modeling.

    Science.gov (United States)

    Duncan, Andrew; Liao, Shuohao; Vejchodský, Tomáš; Erban, Radek; Grima, Ramon

    2015-04-01

    The noisy dynamics of chemical systems is commonly studied using either the chemical master equation (CME) or the chemical Fokker-Planck equation (CFPE). The latter is a continuum approximation of the discrete CME approach. It has recently been shown that for a particular system, the CFPE captures noise-induced multistability predicted by the CME. This phenomenon involves the CME's marginal probability distribution changing from unimodal to multimodal as the system size decreases below a critical value. We here show that the CFPE does not always capture noise-induced multistability. In particular we find simple chemical systems for which the CME predicts noise-induced multistability, whereas the CFPE predicts monostability for all system sizes. PMID:25974443

  18. The atypical chemokine receptor D6 contributes to the development of experimental colitis1

    Science.gov (United States)

    Bordon, Yvonne; Hansell, Chris A. H.; Sester, David P; Clarke, Mairi; Mowat, Allan McI.; Nibbs, Robert J. B.

    2009-01-01

    Pro-inflammatory CC chemokines control leukocyte recruitment and function during inflammation by engaging chemokine receptors expressed on circulating leukocytes. The D6 chemokine receptor can bind several of these chemokines but appears unable to couple to signal transduction pathways or direct cell migration. Instead, D6 has been proposed to act as a chemokine scavenger, removing pro-inflammatory chemokines to dampen leukocyte responses. In this report, we have examined the role of D6 in the colon using the dextran sodium sulphate-induced model of colitis. We show that D6 is expressed in the resting colon, predominantly by stromal cells and B cells, and is up-regulated during colitis. Unexpectedly, D6-deficient mice showed reduced susceptibility to colitis and had less pronounced clinical symptoms associated with this model. D6 deletion had no impact on the level of pro-inflammatory CC chemokines released from cultured colon explants, or on the balance of leukocyte subsets recruited to the inflamed colon. However, late in colitis, inflamed D6-deficient colons showed enhanced production of several pro-inflammatory cytokines, including IFNγ and IL-17A, and there was a marked increase in IL-17A-secreting γδ T cells in the lamina propria. Moreover, antibody-mediated neutralisation of IL-17A worsened the clinical symptoms of colitis at these later stages of the response in D6-deficient, but not wild-type, mice. Thus, D6 can contribute to the development of colitis by regulating IL-17A secretion by γδ T cells in the inflamed colon. PMID:19342683

  19. Inflammatory cytokine gene expression in mesenteric adipose tissue during acute experimental colitis.

    Directory of Open Access Journals (Sweden)

    W Conan Mustain

    Full Text Available BACKGROUND: Production of inflammatory cytokines by mesenteric adipose tissue (MAT has been implicated in the pathogenesis of inflammatory bowel disease (IBD. Animal models of colitis have demonstrated inflammatory changes within MAT, but it is unclear if these changes occur in isolation or as part of a systemic adipose tissue response. It is also unknown what cell types are responsible for cytokine production within MAT. The present study was designed to determine whether cytokine production by MAT during experimental colitis is depot-specific, and also to identify the source of cytokine production within MAT. METHODS: Experimental colitis was induced in 6-month-old C57BL/6 mice by administration of dextran sulfate sodium (2% in drinking water for up to 5 days. The induction of cytokine mRNA within various adipose tissues, including mesenteric, epididymal, and subcutaneous, was analyzed by qRT-PCR. These adipose tissues were also examined for histological evidence of inflammation. The level of cytokine mRNA during acute colitis was compared between mature mesenteric adipocytes, mesenteric stromal vascular fraction (SVF, and mesenteric lymph nodes. RESULTS: During acute colitis, MAT exhibited an increased presence of infiltrating mononuclear cells and fibrotic structures, as well as decreased adipocyte size. The mRNA levels of TNF-α, IL-1β, and IL-6 were significantly increased in MAT but not other adipose tissue depots. Within the MAT, induction of these cytokines was observed mainly in the SVF. CONCLUSIONS: Acute experimental colitis causes a strong site-specific inflammatory response within MAT, which is mediated by cells of the SVF, rather than mature adipocytes or mesenteric lymph nodes.

  20. A new therapeutic association to manage relapsing experimental colitis: Doxycycline plus Saccharomyces boulardii.

    Science.gov (United States)

    Garrido-Mesa, José; Algieri, Francesca; Rodriguez-Nogales, Alba; Utrilla, Maria Pilar; Rodriguez-Cabezas, Maria Elena; Zarzuelo, Antonio; Ocete, Maria Angeles; Garrido-Mesa, Natividad; Galvez, Julio

    2015-07-01

    Immunomodulatory antibiotics have been proposed for the treatment of multifactorial conditions such as inflammatory bowel disease. Probiotics are able to attenuate intestinal inflammation, being considered as safe when chronically administered. The aim of the study was to evaluate the anti-inflammatory effects of doxycycline, a tetracycline with immunomodulatory properties, alone and in association with the probiotic Saccharomyces boulardii CNCMI-745. Doxycycline was assayed both in vitro (Caco-2 epithelial cells and RAW 264.7 macrophages) and in vivo, in the trinitrobenzenesulfonic acid (TNBS) model of rat colitis and the dextran sodium sulfate (DSS) model of mouse colitis. In addition, the anti-inflammatory effect of the association of doxycycline and the probiotic was evaluated in vitro and in vivo in a DSS model of reactivated colitis in mice. Doxycycline displayed immunomodulatory activity in vitro, reducing IL-8 production by intestinal epithelial cells and nitric oxide by macrophages. Doxycycline administration to TNBS-colitic rats (5, 10 and 25 mg/kg) ameliorated the intestinal inflammatory process, being its efficacy comparable to that previously showed by minocycline. Doxycycline treatment was also effective in reducing acute intestinal inflammation in the DSS model of mouse colitis. The association of doxycycline and S. boulardii helped managing colitis in a reactivated model of colitis, by reducing intestinal inflammation and accelerating the recovery and attenuating the relapse. This was evidenced by a reduced disease activity index, colonic tissue damage and expression of inflammatory mediators. This study confirms the intestinal anti-inflammatory activity of doxycycline and supports the potential use of its therapeutic association with S. boulardii for the treatment of inflammatory bowel diseases, in which doxycycline is used to induce remission and long term probiotic administration helps to prevent the relapses. PMID:25917208

  1. Chemically defined diet alters the protective properties of fructo-oligosaccharides and isomalto-oligosaccharides in HLA-B27 transgenic rats.

    Directory of Open Access Journals (Sweden)

    Petya Koleva

    Full Text Available Non-digestible oligosaccharides (NDO were shown to reduce inflammation in experimental colitis, but it remains unclear whether microbiota changes mediate their colitis-modulating effects. This study assessed intestinal microbiota and intestinal inflammation after feeding chemically defined AIN-76A or rat chow diets, with or without supplementation with 8 g/kg body weight of fructo-oligosaccharides (FOS or isomalto-oligosaccharides (IMO. The study used HLA-B27 transgenic rats, a validated model of inflammatory bowel disease (IBD, in a factorial design with 6 treatment groups. Intestinal inflammation and intestinal microbiota were analysed after 12 weeks of treatment. FOS and IMO reduced colitis in animals fed rat chow, but exhibited no anti-inflammatory effect when added to AIN-76A diets. Both NDO induced specific but divergent microbiota changes. Bifidobacteria and Enterobacteriaceae were stimulated by FOS, whereas copy numbers of Clostridium cluster IV were decreased. In addition, higher concentrations of total short-chain fatty acids (SCFA were observed in cecal contents of rats on rat chow compared to the chemically defined diet. AIN-76A increased the relative proportions of propionate, iso-butyrate, valerate and iso-valerate irrespective of the oligosaccharide treatment. The SCFA composition, particularly the relative concentration of iso-butyrate, valerate and iso-valerate, was associated (P ≤ 0.004 and r ≥ 0.4 with increased colitis and IL-1 β concentration of the cecal mucosa. This study demonstrated that the protective effects of fibres on colitis development depend on the diet. Although diets modified specific cecal microbiota, our study indicates that these changes were not associated with colitis reduction. Intestinal inflammation was positively correlated to protein fermentation and negatively correlated with carbohydrate fermentation in the large intestine.

  2. Golimumab in unresponsive ulcerative colitis

    Directory of Open Access Journals (Sweden)

    Lippert E

    2014-05-01

    Full Text Available Elisabeth Lippert, Martina Müller, Claudia Ott University Hospital Regensburg, Department of Internal Medicine I, Regensburg, Germany Abstract: Ulcerative colitis (UC is a chronic inflammation mainly affecting the colon mucosa. It predominantly occurs in younger patients. Until recently, the main goals in the treatment of UC were to temper the symptoms, such as diarrhea, pain, and weight loss, by using mesalazine and steroids. With newer medications, such as immunomodulators (thiopurines and the biologics providing blockade of tumor necrosis factor (TNF, the goals of the therapy in UC have changed to long-term remission and mucosal healing. The first available anti-TNF therapy in UC included infusion therapy with infliximab every few weeks. In 2012, subcutaneously administered adalimumab gained approval for the treatment of UC in Germany. In patients with a mild disease, therapy with mesalazine, orally or topically, can be sufficient. In patients with moderate to severe disease, therapy with azathioprine or anti-TNF is often required to reach disease control; however, this is only efficient in about two-thirds of patients. Some patients either show no response or a lost response while on treatment. So, further medical options are warranted in the treatment of UC. With golimumab, a new approach in the treatment of mild to moderate UC recently became available in Germany and is a promising new option in the therapy regimen for patients with UC. Keywords: anti-TNF, biological therapy, inflammatory bowel disease

  3. Caspase-2 deficiency accelerates chemically induced liver cancer in mice.

    Science.gov (United States)

    Shalini, S; Nikolic, A; Wilson, C H; Puccini, J; Sladojevic, N; Finnie, J; Dorstyn, L; Kumar, S

    2016-10-01

    Aberrant cell death/survival has a critical role in the development of hepatocellular carcinoma (HCC). Caspase-2, a cell death protease, limits oxidative stress and chromosomal instability. To study its role in reactive oxygen species (ROS) and DNA damage-induced liver cancer, we assessed diethylnitrosamine (DEN)-mediated tumour development in caspase-2-deficient (Casp2(-/-)) mice. Following DEN injection in young animals, tumour development was monitored for 10 months. We found that DEN-treated Casp2(-/-) mice have dramatically elevated tumour burden and accelerated tumour progression with increased incidence of HCC, accompanied by higher oxidative damage and inflammation. Furthermore, following acute DEN injection, liver injury, DNA damage, inflammatory cytokine release and hepatocyte proliferation were enhanced in mice lacking caspase-2. Our study demonstrates for the first time that caspase-2 limits the progression of tumourigenesis induced by an ROS producing and DNA damaging reagent. Our findings suggest that after initial DEN-induced DNA damage, caspase-2 may remove aberrant cells to limit liver damage and disease progression. We propose that Casp2(-/-) mice, which are more susceptible to genomic instability, are limited in their ability to respond to DNA damage and thus carry more damaged cells resulting in accelerated tumourigenesis.

  4. Cerebroside D, a glycoceramide compound, improves experimental colitis in mice with multiple targets against activated T lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Xue-Feng; Wu, Xing-Xin; Guo, Wen-Jie; Luo, Qiong [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093 (China); Gu, Yan-Hong [Department of Clinical Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029 (China); Shen, Yan; Tan, Ren-Xiang [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093 (China); Sun, Yang, E-mail: yangsun@nju.edu.cn [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093 (China); Xu, Qiang, E-mail: molpharm@163.com [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093 (China)

    2012-09-15

    In the present paper, we aimed to examine the novel effects of cerebroside D, a glycoceramide compound, on murine experimental colitis. Cerebroside D significantly reduced the weight loss, mortality rate and alleviated the macroscopic and microscopic appearances of colitis induced by dexran sulfate sodium. This compound also decreased the levels of TNF-α, IFN-γ and IL-1β in intestinal tissue of mice with experimental colitis in a concentration-dependent manner, accompanied with markedly increased serum level of IL-10. Cerebroside D inhibited proliferation and induced apoptosis of T cells activated by concanavalin A or anti-CD3 plus anti-CD28 antibodies. The compound did not show an effect on naive lymphocytes but prevented cells from entering S phase and G2/M phase during T cells activation. Moreover, the treatment of cerebroside D led to apoptosis of activated T cells with the cleavage of caspase 3, 9, 12 and PARP. These results showed multiple effects of cerebroside D against activated T cells for a novel approach to treatment of colonic inflammation. Highlights: ► Cerebroside D, a glycoceramide compound, alleviated DSS induced colitis. ► The mechanism of the compound involved multiple effects against activated T cells. ► It regulated cytokine profiles in mice with experimental colitis. ► It prevented T cells from entering S and G2/M phases during activation. ► It led to apoptosis of activated T cells with the cleavage of caspases and PARP.

  5. Induction of colitis in mice with food allergen-specific immune response

    Science.gov (United States)

    Li, Lin-Jing; Zeng, Lu; Li, Xiao-Xi; Mo, Li-Hua; Geng, Xiao-Rui; Zheng, Peng-Yuan; Liu, Zhi-Gang; Feng, Bai-Sui; Yang, Ping-Chang

    2016-09-01

    The pathogenesis of intestinal chronic inflammation is unclear. Food allergy plays an important role in the induction of intestinal inflammation. This study aims to test a hypothesis that food allergy initiates colitis. In this study, BALB/c mice were sensitized to a common food allergen, ovalbumin (OVA) with cholera toxin (CT) as an adjuvant. The colon epithelial barrier function was assessed with Ussing chamber technique. Expression of T cell immunoglobulin mucin domain molecule-4 (TIM4) in dendritic cells was evaluated by flow cytometry, RT-PCR and Western blotting. The results showed that allergen-related colitis was induced in mice as shown by heavy infiltration of inflammatory cells in the colon mucosa, loss of body weight of mice, increases in myeloperoxidase, tumor necrosis factor-α, interleukin-4, OVA-specific IgE in the colon tissue. The colon epithelial barrier function was markedly compromised in colitis group mice, which was mimicked by exposure the colon mucosa to CT in Ussing chamber. High frequency of TIM4+ dendritic cells was detected in the colon mucosa of colitis mice. Exposure of dendritic cells to CT markedly increased the expression of TIM4. We conclude that IBD-like inflammation can be induced in the mouse colon by the food allergen-related immune response.

  6. Intestinal Epithelial Cell Tyrosine Kinase 2 Transduces IL-22 Signals To Protect from Acute Colitis.

    Science.gov (United States)

    Hainzl, Eva; Stockinger, Silvia; Rauch, Isabella; Heider, Susanne; Berry, David; Lassnig, Caroline; Schwab, Clarissa; Rosebrock, Felix; Milinovich, Gabriel; Schlederer, Michaela; Wagner, Michael; Schleper, Christa; Loy, Alexander; Urich, Tim; Kenner, Lukas; Han, Xiaonan; Decker, Thomas; Strobl, Birgit; Müller, Mathias

    2015-11-15

    In the intestinal tract, IL-22 activates STAT3 to promote intestinal epithelial cell (IEC) homeostasis and tissue healing. The mechanism has remained obscure, but we demonstrate that IL-22 acts via tyrosine kinase 2 (Tyk2), a member of the Jak family. Using a mouse model for colitis, we show that Tyk2 deficiency is associated with an altered composition of the gut microbiota and exacerbates inflammatory bowel disease. Colitic Tyk2(-/-) mice have less p-STAT3 in colon tissue and their IECs proliferate less efficiently. Tyk2-deficient primary IECs show reduced p-STAT3 in response to IL-22 stimulation, and expression of IL-22-STAT3 target genes is reduced in IECs from healthy and colitic Tyk2(-/-) mice. Experiments with conditional Tyk2(-/-) mice reveal that IEC-specific depletion of Tyk2 aggravates colitis. Disease symptoms can be alleviated by administering high doses of rIL-22-Fc, indicating that Tyk2 deficiency can be rescued via the IL-22 receptor complex. The pivotal function of Tyk2 in IL-22-dependent colitis was confirmed in Citrobacter rodentium-induced disease. Thus, Tyk2 protects against acute colitis in part by amplifying inflammation-induced epithelial IL-22 signaling to STAT3. PMID:26432894

  7. Infliximab: the evidence for its place in therapy in ulcerative colitis

    Science.gov (United States)

    Van Assche, Gert; Vermeire, Séverine; Rutgeerts, Paul

    2007-01-01

    Introduction: Refractory ulcerative colitis has a high, unmet medical need for avoiding steroid dependency and avoiding colectomy. Controlled trials with biologic agents have recently been reported. Aims: We aimed to review the current evidence supporting the use of the monoclonal antitumor necrosis factor antibody, infliximab, in active ulcerative colitis and determine its current place in therapy. Evidence review: Although faced with initial conflicting data particularly in steroid-refractory patients, two large, placebo-controlled trials have shown that intravenous infliximab induces and maintains clinical improvement in a clinically significant proportion of patients when used with scheduled re-treatment. Infliximab also spares steroids and induces endoscopic remission in moderately ill patients. In fulminant colitis unresponsive to intravenous steroids, one placebo-controlled trial indicates that infliximab is able to prevent colectomy in this patient population. Evidence for cost effectiveness and avoidance of colectomy long term are still lacking. Place in therapy: Infliximab 5 mg/kg induction at 0, 2, and 6 weeks, and every 8 weeks thereafter should be considered in patients with moderately to severely active ulcerative colitis failing medical therapy. Steroid-dependent and steroid-refractory patients also qualify for infliximab therapy. PMID:21221182

  8. A Complicated Case of Tacrolimus-Induced Rapid Remission after Cesarean Section in the Early Third Trimester for Refractory Severe Ulcerative Colitis Flaring in the Initial Period of Gestation

    Directory of Open Access Journals (Sweden)

    Takashi Mizushima

    2011-04-01

    Full Text Available A 36-year-old woman who had been diagnosed with ulcerative colitis at the age of 17 years was referred to our hospital because of severe abdominal pain and repeated bloody diarrhea that persisted during pregnancy despite combination therapy with high-dose corticosteroids and weekly granulocyte and monocyte adsorptive apheresis (GMA. She underwent combination therapy consisting of high-dose corticosteroids, intensive GMA (two sessions per week and vancomycin, which was used to eradicate Clostridium difficile, under total parenteral nutrition control until the estimated weight of her fetus reached 1,000 g. This combination therapy was partially successful, resulting in almost complete disappearance of abdominal pain and a marked decrease in stool frequency. However bloody diarrhea persisted and the patient developed anemia and hypoalbuminemia and was unable to prolong her gestation time. Cesarean section was conducted at 28 weeks of gestation without any congenital abnormalities or neurological defects. Oral administration of tacrolimus was begun 7 days after cesarean section, which was followed by rapid induction of remission. Corticosteroids were then gradually tapered off. Tacrolimus is one therapeutic option after cesarean section in pregnant patients who do not respond well to GMA and high-dose corticosteroids for persistent active ulcerative colitis.

  9. Amyloid Goiter Secondary to Ulcerative Colitis

    Directory of Open Access Journals (Sweden)

    Bunyamin Aydin

    2016-01-01

    Full Text Available Diffuse amyloid goiter (AG is an entity characterized by the deposition of amyloid in the thyroid gland. AG may be associated with either primary or secondary amyloidosis. Secondary amyloidosis is rarely caused by inflammatory bowel diseases. Secondary amyloidosis is relatively more common in the patients with Crohn’s disease, whereas it is highly rare in patients with ulcerative colitis. Diffuse amyloid goiter caused by ulcerative colitis is also a rare condition. In the presence of amyloid in the thyroid gland, medullary thyroid cancer should be kept in mind in the differential diagnosis. Imaging techniques and biochemical tests are not very helpful in the diagnosis of secondary amyloid goiter and the definitive diagnosis is established based on the histopathologic analysis and histochemical staining techniques. In this report, we present a 35-year-old male patient with diffuse amyloid goiter caused by secondary amyloidosis associated with ulcerative colitis.

  10. Diagnosis and management of microscopic colitis

    Institute of Scientific and Technical Information of China (English)

    Curt Tysk; Johan Bohr; Nils Nyhlin; Anna Wickbom; Sune Eriksson

    2008-01-01

    Microscopic colitis,comprising collagenous and lymphocytic colitis,is characterized clinically by chronic watery diarrhea,and a macroscopically normal colonic mucosa where diagnostic histopathological features are seen on microscopic examination.The annual incidence of each disorder is 4-6/100000 inhabitants,with a peak incidence in 60-70-year-old individuals and a noticeable female predominance for collagenous colitis.The etiology is unknown.Chronic diarrhea,abdominal pain,weight loss,fatigue and fecal incontinence are common symptoms,which impair the health-related quality of life of the patient.There is an association with other autoimmune disorders such as celiac disease,diabetes mellitus,thyroid disorders and arthritis.Budesonide is the best-documented shortterm treatment,but the optimal long-term strategy needs further study.The long-term prognosis is good and the risk of complications including colonic cancer is low.

  11. Amyloid Goiter Secondary to Ulcerative Colitis.

    Science.gov (United States)

    Aydin, Bunyamin; Koca, Yavuz Savas; Koca, Tugba; Yildiz, Ihsan; Gerek Celikden, Sevda; Ciris, Metin

    2016-01-01

    Diffuse amyloid goiter (AG) is an entity characterized by the deposition of amyloid in the thyroid gland. AG may be associated with either primary or secondary amyloidosis. Secondary amyloidosis is rarely caused by inflammatory bowel diseases. Secondary amyloidosis is relatively more common in the patients with Crohn's disease, whereas it is highly rare in patients with ulcerative colitis. Diffuse amyloid goiter caused by ulcerative colitis is also a rare condition. In the presence of amyloid in the thyroid gland, medullary thyroid cancer should be kept in mind in the differential diagnosis. Imaging techniques and biochemical tests are not very helpful in the diagnosis of secondary amyloid goiter and the definitive diagnosis is established based on the histopathologic analysis and histochemical staining techniques. In this report, we present a 35-year-old male patient with diffuse amyloid goiter caused by secondary amyloidosis associated with ulcerative colitis. PMID:27051538

  12. Collagenous gastritis associated with lymphocytic colitis.

    Science.gov (United States)

    Groisman, G M; Meyers, S; Harpaz, N

    1996-03-01

    Collagenous sprue and collagenous colitis are two well-recognized idiopathic enteritides whose defining histologic attribute is fibrous thickening of the subepithelial basement membrane. Analogous changes in gastric mucosa seem to be quite rare. The term "collagenous gastritis" was recently applied for the first time to an isolated case of refractory gastritis in which distinctive subepithelial gastric fibrosis was noted. We report an additional case of this entity in a 35-year-old woman with refractory dyspepsia. In contrast to the earlier case of collagenous gastritis, our patient also had lymphocytic colitis, a type of colitis associated with watery diarrhea. Collagenous gastritis appears to be a distinct clinicopathologic entity, the histologic changes of which should be sought in patients with unexplained dyspepsia. Increased awareness of this condition and its possible clinical correlates may provide clues to its etiology and pathogenesis. PMID:8742654

  13. Infliximab to treat severe ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Dídia Bisamra Cury; Marcelo de Souza Cury; Geraldo Vinicius Hemerly Elias; Sender Jankiel Mizsputen

    2009-01-01

    A 48-year-old female with severe ulcerative colitis refractory to conventional therapy was referred to our facility for management. The patient showed extensive ulcerative colitis since the age of 20 years and had failed therapy with 5-aminosalicylic acid agents and azathioprine. The disease remained active despite treatment with steroids and cyclosporine. The clinical and endoscopic parameters were consistent with severe disease. Infectious precipitants were ruled out. Given the severity of the disease and in order to avoid a colectomy, we started the patient on infliximab therapy. A dramatic clinical and endoscopic response was observed and she remained in remission at the end of a 1-year follow-up period. We discuss findings in the literature regarding the use of infliximab therapy in patients with ulcerative colitis who have failed steroids and cyclosporine.

  14. Genesis of anxiety, depression, and ongoing abdominal discomfort in ulcerative colitis-like colon inflammation

    OpenAIRE

    Chen, Jinghong; Winston, John H.; Fu, Yu; Guptarak, Jutatip; Jensen, Kathryn L.; Shi, Xuan-Zheng; Green, Thomas A; Sarna, Sushil K.

    2014-01-01

    Psychological disorders are prevalent in patients with inflammatory bowel disease; the underlying mechanisms remain unknown. We tested the hypothesis that ulcerative colitis-like inflammation induced by dextran sodium sulfate (DSS) exacerbates the ongoing spontaneous activity in colon-projecting afferent neurons that induces abdominal discomfort and anxiety, and depressive-like behaviors in rats. In this study, we used the conditioned place preference and standard tests for anxiety- and depre...

  15. Specific probiotic dietary supplementation leads to different effects during remission and relapse in murine chronic colitis.

    Science.gov (United States)

    Zheng, B; van Bergenhenegouwen, J; van de Kant, H J G; Folkerts, G; Garssen, J; Vos, A P; Morgan, M E; Kraneveld, A D

    2016-01-01

    Although interest in using probiotics to prevent and treat intestinal diseases is increasing, the effects of specific probiotic strains still remain unclear. Here, we assess the therapeutic effects of two probiotic strains, Lactobacillus rhamnosus NutRes 1 and Bifidobacterium breve NutRes 204 on a dextran sodium sulphate (DSS)-induced chronic murine colitis model. The chronic colitis was induced by two DSS treatment cycles with a rest period of 10 days (the remission or resolution phase). The probiotic supplementation was started during the resolution phase, after the first DSS treatment cycle, and continued until the end of the experiment. In addition to clinical observations made during the experiment, cellular infiltration was measured along with mRNA expression of pro-inflammatory cytokines, T cell-associated cytokines, and Toll like receptors (TLR) in the inflamed colon after second DSS treatment cycle. L. rhamnosus, but not B. breve, rapidly and effectively improved the DSS-induced bloody diarrhoea during the resolution phase. However, a contradictory effect by both probiotic strains on the faecal condition was found after re-induction of colitis. The worsening of the faecal condition was accompanied by a reduced number of neutrophils and increased expression of interferon-γ in the colons of DSS-treated mice. Furthermore, an increased expression of TLR2, TLR6 and pro-inflammatory markers including chemokine (C-C motif) ligand 2, interleukin (IL)-1β, tumour necrosis factor α and IL-6 was found in DSS-treated mice with L. rhamnosus supplementation. These results indicate that therapeutic administration of specific probiotics might be beneficial during the resolution phase of colitis. However, caution should be taken as specific probiotic treatments reduce neutrophil influx, which may be the reason of exacerbation of chronic colitis. PMID:26645352

  16. Antioxidative potential of a combined therapy of anti TNFα and Zn acetate in experimental colitis

    Institute of Scientific and Technical Information of China (English)

    Michela Barollo; Giacomo Carlo Sturniolo; Valentina Medici; Renata D'Incà; Antara Banerjee; Giuseppe Ingravallo; Marco Scarpa; Surajit Patak; Cesare Ruffolo; Romilda Cardin

    2011-01-01

    AIM: To evaluate whether combination therapy with anti-tumour necrosis factor α (TNFα). Zantibody and Zn acetate is beneficial in dextran sodium sulphate(DSS) colitis. METHODS: Colitis was induced in CD1-Swiss mice with 5% DS for 7 d. The exp erimental mice were th en randomised into the following subgroups: standard diet + DSS treated (induced colitis group); standard diet + DSS + subcutaneous 25. Μg anti-TNFα treated group; Zn acetate treated group + DSS + subcutaneous 25 μg anti-TNFα; standard diet + DS + subcut aneou s 6.25 μg anti-TNFα treated group and Zn acetate treated group + DS + subcut aneou s 6.25 μg anti-TNFα. Each group of mice was matched with a similar group of sham contro l animals. Macro scop ic and histo logical featur es were scor ed blindly. Homo genates of th e colonic mu cosa were assessed for myeloperoxidase activity as a biochemical marker of inflamm ation and DNA addu cts (8OHdG) as a measur e of ox idative damage. RESULTS: DSS produced submucosal erosions, ulcers, inflammatory cell infiltration and cryptic abscesses which were reduced in both groups of mice receiving either anti-TNFα alone or com bined with zinc. The effect was more pronounced in the latter group. .(vs Zn diet, P < 0.02).Myeloperoxidase activity (vs controls, P < 0.02) and DNA addu cts, greatly elevated in th e DSS fed colitis group (vs controls,. P < 0.05), were significantly redu ced in th e tr eated group s, with a mor e remarkable effect in the group receiving combined therapy (vs standard diet,. P < 0.04). CONCLUSION: DSS induces colonic inflammation which is modulated by the administration of anti-TNFα. Combining anti-TNFα Zwith Zn acetate offers marginal benefit in colitis severity.

  17. Antioxidative potential of a combined therapy of anti TNFα and Zn acetate in experimental colitis

    Science.gov (United States)

    Barollo, Michela; Medici, Valentina; D’Incà, Renata; Banerjee, Antara; Ingravallo, Giuseppe; Scarpa, Marco; Patak, Surajit; Ruffolo, Cesare; Cardin, Romilda; Sturniolo, Giacomo Carlo

    2011-01-01

    AIM: To evaluate whether combination therapy with anti-tumour necrosis factor α (TNFα) antibody and Zn acetate is beneficial in dextran sodium sulphate (DSS) colitis. METHODS: Colitis was induced in CD1-Swiss mice with 5% DSS for 7 d. The experimental mice were then randomised into the following subgroups: standard diet + DSS treated (induced colitis group); standard diet + DSS + subcutaneous 25 μg anti-TNFα treated group; Zn acetate treated group + DSS + subcutaneous 25 μg anti-TNFα; standard diet + DSS + subcutaneous 6.25 μg anti-TNFα treated group and Zn acetate treated group + DSS + subcutaneous 6.25 μg anti-TNFα. Each group of mice was matched with a similar group of sham control animals. Macroscopic and histological features were scored blindly. Homogenates of the colonic mucosa were assessed for myeloperoxidase activity as a biochemical marker of inflammation and DNA adducts (8OH-dG) as a measure of oxidative damage. RESULTS: DSS produced submucosal erosions, ulcers, inflammatory cell infiltration and cryptic abscesses which were reduced in both groups of mice receiving either anti-TNFα alone or combined with zinc. The effect was more pronounced in the latter group (vs Zn diet, P < 0.02). Myeloperoxidase activity (vs controls, P < 0.02) and DNA adducts, greatly elevated in the DSS fed colitis group (vs controls, P < 0.05), were significantly reduced in the treated groups, with a more remarkable effect in the group receiving combined therapy (vs standard diet, P < 0.04). CONCLUSION: DSS induces colonic inflammation which is modulated by the administration of anti-TNFα. Combining anti-TNFα with Zn acetate offers marginal benefit in colitis severity. PMID:22039323

  18. Effects of laser therapy on cytokines in rats with oxazolone induced ulcerative colitis%激光治疗对(恶)唑酮诱导的溃疡性结肠炎大鼠细胞因子的影响

    Institute of Scientific and Technical Information of China (English)

    杜金刚; 刘畅格; 黄力平; 李猛; 韩玉山; 韩秀娟

    2011-01-01

    目的 探讨低能量激光治疗溃疡性结肠炎(UC)的分子机制,观察治疗前、后细胞因子肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和白细胞介素-10(IL-10)变化,为临床治疗提供依据.方法 将健康成年雄性SD大鼠30只分为正常组(6只)、UC对照组(8只)、200 mW激光治疗组(8只)和400 mW激光治疗组(8只).采用改良的(嗯)唑酮致敏法制备大鼠UC模型.造模后对2个激光治疗组大鼠分别以功率为200 mW与400 mW的砷铝化镓半导体激光进行治疗,每次照射10 min,每日1次,连续10 d.治疗后将大鼠处死,酶联免疫吸附分析( ELISA)测定各组大鼠血清和组织匀浆液中TNF-α、IL-6、IL-10的含量.结果 UC对照组大鼠与正常组比较,体重显著降低(P<0.01),黏液脓血便,血清和结肠组织匀浆中TNF-α和IL-6含量显著升高(P<0.05),IL-10显著下降(P<0.01),造模成功.激光治疗后,大鼠体重和大便性状显著好转;400 mW激光治疗组血清和结肠组织匀浆中TNF-α、IL-6显著降低(P<0.01),IL-10显著提高(P<0.05),接近正常水平;200 mW激光治疗组血清中TNF-d和IL-6显著降低(P<0.05),结肠组织匀浆中IL-6显著降低(P<0.01),TNF-α降低不显著(P>0.05),血清和结肠组织匀浆中IL-10提高没有达到显著性水平(P>0.05).结论 400 mW砷铝化镓半导体激光能够有效地双向调节(嗯)唑酮诱导的UC大鼠细胞因子,减低致炎细胞因子,增加抗炎因子作用,可能是低能量激光治疗UC产生较优疗效的机制之一.%Objective To explore the effects and molecular mechanisms of laser therapy on serum and colon tumor necrosis factor α (TNF-α),interleukin-6 (IL-6) and interleukin-10 (IL-10) in rats with oxazolone induced ulcerative colitis (UC).Methods Thirty adult male SD rats were randomly divided into four groups:a normal group ( n =6),a UC model group ( n =8 ),a 400 mW laser treatment group ( n =8 ) and a 200 mW laser treatment group ( n =8 ).Odified

  19. Small-bowel permeability in collagenous colitis

    DEFF Research Database (Denmark)

    Wildt, Signe; Madsen, Jan L; Rumessen, Jüri J

    2006-01-01

    OBJECTIVE: Collagenous colitis (CC) is a chronic inflammatory bowel disease that affects the colon. However, some patients with CC present with accompanying pathologic small-bowel manifestations such as coeliac disease, defects in bile acid absorption and histopathologic changes in small-intestin......OBJECTIVE: Collagenous colitis (CC) is a chronic inflammatory bowel disease that affects the colon. However, some patients with CC present with accompanying pathologic small-bowel manifestations such as coeliac disease, defects in bile acid absorption and histopathologic changes in small...

  20. Ethyl pyruvate ameliorates experimental colitis in mice by inhibiting the HMGB1-Th17 and Th1/Tc1 responses.

    Science.gov (United States)

    Guo, Xianghua; Guo, Runhua; Luo, Xia; Zhou, Lian

    2015-12-01

    Ethyl pyruvate (EP), a simple lipophilic pyruvate ester, has demonstrated protective effects against murine colitis through inhibition the release of inflammatory factor high-mobility group protein box 1 (HMGB1). HMGB1 has been implicated in several autoimmune diseases by inducing Thl and Thl7 cells activation. This study was designed to investigate whether EP amelioration of murine colitis is related to the blocking of the HMGB1-Th17/Thl pathway. We induced murine colitis by intrarectal administration of 2, 4, 6-trinitrobenzene sulfonic acid (TNBS). Ethyl pyruvate was injected intraperitoneally once a day for 7days. One week after intrarectal challenge with TNBS, HMGB1, IL-17 and IFN-γ protein levels were remarkably increased following severe colon inflammation. Meanwhile, excessive infiltration of Th17 cells in colonic tissues, and an upregulated proportion of Th17 and Th1/Tc1 cells in the spleen and mesenteric lymph nodes (MLN) were found in the TNBS-treated group compared to the control group. Treatment with the HMGB1 inhibitor EP not only remarkably improved colon pathological damage, but also significantly reduced the number of Th17 cells in the local tissues of the colitis-induced mice. Furthermore, the percentage of Th1/Tc1 and Th17 cells in the spleen and MLN, as well as levels of serum IFN-γ and IL-17A, were all markedly decreased in the EP-treated group. Moreover, in vitro, our results showed that EP in a dose dependent manner inhibited HMGB1 release induced by LPS from CT26 cells (murine colon adenocarcinoma cell line). These results suggest that HMGB1 contributes to the development of murine colitis by promoting the Th17 and Th1/Tc1 responses, and that EP can significantly inhibit HMGB1-Th17 and Thl/Tc1 pathway activation, which may provide better protection to mice with TNBS-induced colitis.

  1. Drug therapy for ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Chang-Tai Xu; Shu-Yong Meng; Bo-Rong Pan

    2004-01-01

    Ulcerative colitis (UC) is an inflammatory destructive disease of the large intestine occurred usually in the rectum and lower part of the colon as well as the entire colon. Drug therapy is not the only choice for UC treatment and medical management should be as a comprehensive whole.Azulfidine, Asacol, Pentasa, Dipentum, and Rowasa all contain 5-aminosalicylic acid (5-ASA), which is the topical anti-inflammatory ingredient. Pentasa is more commonly used in treating Crohn's ileitis because Pentasa capsules release more 5-ASA into the small intestine than Asacol tablets. Pentasa can also be used for treating mild to moderate UC. Rowasa enemas are safe and effective in treating ulcerative proctitis and proctosigmoiditis. The sulfafree 5-ASA agents (Asacol, Pentasa, Dipentum and Rowasa) have fewer side effects than sulfa-containing Azulfidine. In UC patients with moderate to severe disease and in patients who failed to respond to 5-ASA compounds,systemic (oral) corticosteroids should be used. Systemic corticosteroids (prednisone, prednisolone, cortisone, etc.)are potent and fast-acting drugs for treating UC, Crohn's ileitis and ileocolitis. Systemic corticosteroids are not effective in maintaining remission in patients with UC.Serious side effects can result from prolonged corticosteroid treatment. To minimize side effects, corticosteroids should be gradually reduced as soon as the disease remission is achieved. In patients with corticosteroid-dependent or unresponsive to corticosteroid treatment, surgery or immunomodulator is considered. Immunomodulators used for treating severe UC include azathioprine/6-MP,methotrexate, and cyclosporine. Integrated traditional Chinese and Western medicine is safe and effective in maintaining remission in patients with UC.

  2. Hygienic grooming is induced by contact chemicals in Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Aya eYanagawa

    2014-07-01

    Full Text Available In social insects, grooming is considered as a behavioral defense against pathogen and parasite infections since it contributes to remove microbes from their cuticle. However, stimuli which trigger this behavior are not well characterized yet. We examined if activating contact chemoreceptive sensilla could trigger grooming activities in Drosophila melanogaster. We monitored the grooming responses of decapitated flies to compounds known to activate the immune system e.g. dead Escherichia coli (Ec and lipopolysaccharides (LPS, and to tastants such as quinine, sucrose, and salt. LPS, quinine and Ec were quite effective in triggering grooming movements when touching the distal border of the wings and the legs, while sucrose had no effect. Contact chemoreceptors are necessary and sufficient to elicit such responses, as grooming could not be elicited by LPS in poxn mutants deprived of external taste sensilla, and as grooming was elicited by light when a channel rhodopsin receptor was expressed in bitter-sensitive cells expressing Gr33a. Contact chemoreceptors distributed along the distal border of the wings respond to these tastants by an increased spiking activity, in response to quinine, Ec, LPS, sucrose and KCl. These results demonstrate for the first time that bacterial compounds trigger grooming activities in D. melanogaster, and indicate that contact chemoreceptors located on the wings participate to the detection of such chemicals.

  3. Fecal calprotectin and ulcerative colitis endoscopic activity index as indicators of mucosal healing in ulcerative colitis.

    Science.gov (United States)

    Taghvaei, Tarang; Maleki, Iradj; Nagshvar, Farshad; Fakheri, Hafez; Hosseini, Vahid; Valizadeh, Seyed Mohammad; Neishaboori, Hassan

    2015-04-01

    Ulcerative colitis (UC) is a chronic, idiopathic, inflammatory large bowel disease with recurrent variable periods of exacerbation. The aim of the current study is to evaluate the correlation of UCEIS with fecal calprotectin (FC) level to assess disease activity in UC patients in order to determine whether FC can prognosticate clinical outcome and disease activity of UC instead of colonoscopic evaluation. Our endoscopic investigations revealed the extension of UC as the following: proctitis (11.6%), procto-sigmoiditis (18.5%), left-sided colitis (15.8%), extensive colitis (11.7%), and normal endoscopy (42.4%). Conclusively, we suggest that FC can be used as a reliable tool to evaluate disease activity in ulcerative colitis patients. Moreover, our findings indicate a significant correlation between FC level and mucosal healing. PMID:25366383

  4. Triptolide downregulates Rac1 and the JAK/STAT3 pathway and inhibits colitis-related colon cancer progression

    DEFF Research Database (Denmark)

    Wang, Zhipeng; Jin, Haifeng; Xu, Ruodan;

    2009-01-01

    ability to block progress of colitis to colon cancer, and its molecular mechanism of action are investigated. A mouse model for colitis-induced colorectal cancer was used to test the effect of triptolide on cancer progression. Treatment of mice with triptolide decreased the incidence of colon cancer...... formation, and increased survival rate. Moreover, triptolide decreased the incidence of tumors in nude mice inoculated with cultured colon cancer cells dose-dependently. In vitro, triptolide inhibited the proliferation, migration and colony formation of colon cancer cells. Secretion of IL6 and levels of JAK....... This suggests that triptolide might be a candidate for prevention of colitis induced colon cancer because it reduces inflammation and prevents tumor formation and development....

  5. Surface chemical reactions induced by well-controlled molecular beams: translational energy and molecular orientation control

    Energy Technology Data Exchange (ETDEWEB)

    Okada, Michio, E-mail: okada@chem.sci.osaka-u.ac.j, E-mail: mokada@cw.osaka-u.ac.j [Renovation Center of Instruments for Science Education and Technology, Osaka University, Mihogaoka 8-1, Ibaraki, Osaka 567-0047 and 1-2 Machikaneyama-cho, Toyonaka, Osaka 560-0043 (Japan)

    2010-07-07

    I review our recent studies of chemical reactions on single-crystalline Cu and Si surfaces induced by hyperthermal oxygen molecular beams and by oriented molecular beams, respectively. Studies of oxide formation on Cu induced by hyperthermal molecular beams suggest that the translational energy of the incident molecules plays a significant role. The use of hyperthermal molecular beams enables us to open up new chemical reaction paths, and to develop new methods for the fabrication of thin films. Oriented molecular beams also demonstrate the possibility for controlling surface chemical reactions by varying the orientation of the incident molecules. The steric effects found on Si surfaces hint at new ways of achieving material fabrication on Si surfaces. Controlling the initial conditions of incoming molecules is a powerful tool for creating new materials on surfaces with well-controlled chemical reactions. (topical review)

  6. Early aggressive therapy for severe extensive ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    De-Jun Cui

    2009-01-01

    The current ulcerative colitis (UC) treatment algorithm involves a step-up therapeutic strategy, mainly aiming at inducing and maintaining its clinical remission.Although this therapeutic strategy may seem to be cost-efficient and reduce the risk of side effects,recent trials and case reports have shown that topdown therapy using infliximab induces a rapid clinical response, enhances patient quality of life, promotes mucosal healing, reduces surgeries and indirect cost of treatment for patients with severe UC. Moreover,since long-term treatment with infliximab is safe and well tolerated, early aggressive top-down therapeutic strategy may be a more effective approach, at least in a subgroup of severe extensive UC patients.

  7. Glutamine Supplementation Attenuates Expressions of Adhesion Molecules and Chemokine Receptors on T Cells in a Murine Model of Acute Colitis

    Directory of Open Access Journals (Sweden)

    Yu-Chen Hou

    2014-01-01

    Full Text Available Background. Migration of T cells into the colon plays a major role in the pathogenesis in inflammatory bowel disease. This study investigated the effects of glutamine (Gln supplementation on chemokine receptors and adhesion molecules expressed by T cells in mice with dextran sulfate sodium- (DSS- induced colitis. Methods. C57BL/6 mice were fed either a standard diet or a Gln diet replacing 25% of the total nitrogen. After being fed the diets for 5 days, half of the mice from both groups were given 1.5% DSS in drinking water to induce colitis. Mice were killed after 5 days of DSS exposure. Results. DSS colitis resulted in higher expression levels of P-selectin glycoprotein ligand- (PSGL- 1, leukocyte function-associated antigen- (LFA- 1, and C-C chemokine receptor type 9 (CCR9 by T helper (Th and cytotoxic T (Tc cells, and mRNA levels of endothelial adhesion molecules in colons were upregulated. Gln supplementation decreased expressions of PSGL-1, LFA-1, and CCR9 by Th cells. Colonic gene expressions of endothelial adhesion molecules were also lower in Gln-colitis mice. Histological finding showed that colon infiltrating Th cells were less in the DSS group with Gln administration. Conclusions. Gln supplementation may ameliorate the inflammation of colitis possibly via suppression of T cell migration.

  8. Two cases of rectal cancer accompanied with radiation colitis

    International Nuclear Information System (INIS)

    This paper presents two cases of rectal cancer accompanied with radiation colitis. Case 1 was a 53-year-old woman, who had a history of undergoing radiation therapy for a uterine cervical cancer 11 years before. She was seen at the hospital because of constipation and pointed out a IIa-like lesion on the rectum by colonoscopy. Abdominoperineal resection was performed. The surgical specimen showed the IIa-like lesion on the rectum. Pathological findings revealed well-differentiated adenocarcinoma. Immunohistochemical staining of p53 showed positive cells in atrophic glands. Case 2 was a 62-year-old woman complaining of diarrhea. There was a previous history of receiving radiation therapy for a uterine cancer 20 years before. Colonoscopy showed a Borrmann type 2 cancer on the rectum. Abdominoperineal resection was performed. Histological findings revealed moderately differentiated adenocarcinoma invading to the propria muscle. The features of radiation colitis were observed around the cancer in the two cases which provided a clue to diagnose the lesions with radiation-induced cancer. (author)

  9. Eosinophilic Colitis: University of Minnesota Experience and Literature Review

    Directory of Open Access Journals (Sweden)

    Wolfgang B. Gaertner

    2011-01-01

    Full Text Available Eosinophilic colitis is a rare form of primary eosinophilic gastrointestinal disease that is poorly understood. Neonates and young adults are more frequently affected. Clinical presentation is highly variable depending on the depth of inflammatory response (mucosal, transmural, or serosal. The pathophysiology of eosinophilic colitis is unclear but is suspected to be related to a hypersensitivity reaction given its correlation with other atopic disorders and clinical response to corticosteroid therapy. Diagnosis is that of exclusion and differential diagnoses are many because colonic tissue eosinophilia may occur with other colitides (parasitic, drug-induced, inflammatory bowel disease, and various connective tissue disorders. Similar to other eosinophilic gastrointestinal disorders, steroid-based therapy and diet modification achieve very good and durable responses. In this paper, we present our experience with this rare pathology. Five patients (3 pediatric and 2 adults presented with diarrhea and hematochezia. Mean age at presentation was 26 years. Mean duration of symptoms before pathologic diagnosis was 8 months. Mean eosinophil count per patient was 31 per high-power field. The pediatric patients responded very well to dietary modifications, with no recurrences. The adult patients were treated with steroids and did not respond. Overall mean followup was 22 (range, 2–48 months.

  10. Increased capsaicin-induced secondary hyperalgesia in patients with multiple chemical sensitivity

    DEFF Research Database (Denmark)

    Holst, Helle; Arendt-Nielsen, Lars; Mosbech, Holger;

    2011-01-01

    in experimental pain models to provoke peripheral and central sensitization. In patients with symptoms elicited by odorous chemicals capsaicin-induced secondary hyperalgesia and temporal summation were assessed as markers for abnormal central nociceptive processing together with neurogenic inflammation (flare).......the underlying cause of pathophysiological mechanisms triggering multiple chemical sensitivity (MCS) remains disputed.Recently, alterations in the central nervous system, for example,central sensitization, similar to various chronic pain disorders, have been suggested. Capsaicin is used...

  11. Chemically-induced Jahn-Teller ordering on manganite surfaces

    Science.gov (United States)

    Gai, Zheng; Lin, Wenzhi; Burton, J. D.; Tsymbal, Evgeny Y.; Fuchigami, K.; Shen, Jian; Snijders, P. C.; Ward, T. Z.; Jesse, Stephen; Kalinin, Sergei V.; Baddorf, A. P.

    2014-03-01

    Physical and electrochemical phenomena at the surfaces of transition metal oxides and their coupling to local functionality remains one of the enigmas of condensed matter physics. Understanding the emergent physical phenomena at surfaces requires the capability to probe the local composition, map order parameter fields, and establish their coupling to electronic properties. Here we demonstrate that measuring the sub 30 pm displacements of atoms from high-symmetry positions in the atomically resolved scanning tunneling microscopy (STM) allows the physical order parameter fields to be visualized in real space on the single atom level. Here, this local crystallographic analysis is applied to the in-situ grown manganite surfaces. In particular, using direct bond-angle mapping we report direct observation of structural domains on manganite surfaces, and trace their origin to surface-chemistry-induced stabilization of ordered Jahn-Teller displacements. Density functional calculations provide insight into the intriguing interplay between the various degrees of freedom now resolved on the atomic level. Research was supported by MSED and CNMS, which are sponsored at Oak Ridge National Laboratory by the Office of Basic Energy Sciences, U.S. Department of Energy.

  12. Chemically induced Jahn-Teller ordering on manganite surfaces.

    Science.gov (United States)

    Gai, Zheng; Lin, Wenzhi; Burton, J D; Fuchigami, K; Snijders, P C; Ward, T Z; Tsymbal, Evgeny Y; Shen, J; Jesse, Stephen; Kalinin, Sergei V; Baddorf, Arthur P

    2014-01-01

    Physical and electrochemical phenomena at the surfaces of transition metal oxides and their coupling to local functionality remains one of the enigmas of condensed matter physics. Understanding the emergent physical phenomena at surfaces requires the capability to probe the local composition, map order parameter fields and establish their coupling to electronic properties. Here we demonstrate that measuring the sub-30-pm displacements of atoms from high-symmetry positions in the atomically resolved scanning tunnelling microscopy allows the physical order parameter fields to be visualized in real space on the single-atom level. Here, this local crystallographic analysis is applied to the in-situ-grown manganite surfaces. In particular, using direct bond-angle mapping we report direct observation of structural domains on manganite surfaces, and trace their origin to surface-chemistry-induced stabilization of ordered Jahn-Teller displacements. Density functional calculations provide insight into the intriguing interplay between the various degrees of freedom now resolved on the atomic level. PMID:25058540

  13. Suppressive effects of coffee on the SOS responses induced by UV and chemical mutagens

    International Nuclear Information System (INIS)

    SOS-inducing activity of UV or chemical mutagens was strongly suppressed by instant coffee in Salmonella typhimurium TA1535/pSK1002. As decaffeinated instant coffee showed a similarly strong suppressive effect, it would seem that caffeine, a known inhibitor of SOS responses, is not responsible for the effect observed. The suppression was also shown by freshly brewed coffee extracts. However, the suppression was absent in green coffee-bean extracts. These results suggest that coffee contains some substance(s) which, apart from caffeine, suppresses SOS-inducing activity of UV or chemical mutagens and that the suppressive substance(s) are produced by roasting coffee beans. (Auth.)

  14. Single Nucleotide Polymorphisms that Increase Expression of the GTPase RAC1 are Associated with Ulcerative Colitis

    Science.gov (United States)

    Muise, Aleixo M; Walters, Thomas; Xu, Wei; Shen-Tu, Grace; Guo, Cong-Hui; Fattouh, Ramzi; Lam, Grace Y; Wolters, Victorien M; Bennitz, Joshua; Van Limbergen, Johan; Renbaum, Paul; Kasirer, Yair; Ngan, Bo-Yee; Turner, Dan; Denson, Lee A; Sherman, Philip M; Duerr, Richard H; Cho, Judy; Lees, Charlie W; Satsangi, Jack; Wilson, David C; Paterson, Andrew D; Griffiths, Anne M; Glogauer, Michael; Silverberg, Mark S; Brumell, John H

    2011-01-01

    Background & Aims RAC1 is a GTPase that has an evolutionarily conserved role in coordinating immune defenses, from plants to mammals. Chronic inflammatory bowel diseases (IBD) are associated with dysregulation of immune defenses. We studied the role of RAC1 in IBD using human genetic and functional studies and animal models of colitis. Methods We used a candidate gene approach to HapMap-Tag single nucleotide polymorphisms (SNPs) in a discovery cohort; findings were confirmed in 2 additional cohorts. RAC1 mRNA expression was examined from peripheral blood cells of patients. Colitis was induced in mice with conditional disruption of Rac1 in phagocytes by administration of dextran sulphate sodium (DSS). Results We observed a genetic association between RAC1 with ulcerative colitis (UC) in a discovery cohort, 2 independent replication cohorts, and in combined analysis for the SNPs rs10951982 (Pcombined UC = 3.3 × 10–8, odds ratio [OR]=1.43 [1.26–1.63]) and rs4720672 (Pcombined UC=4.7 × 10–6, OR=1.36 [1.19–1.58]). Patients with IBD who had the rs10951982 risk allele had increased expression of RAC1, compared to those without this allele. Conditional disruption of Rac1 in macrophage and neutrophils of mice protected them against DSS-induced colitis. Conclusion Studies of human tissue samples and knockout mice demonstrated a role for the GTPase RAC1 in the development of UC; increased expression of RAC1 was associated with susceptibility to colitis. PMID:21684284

  15. Validation and optimization of experimental colitis induction in rats using 2, 4, 6-trinitrobenzene sulfonic acid.

    Science.gov (United States)

    Motavallian-Naeini, A; Andalib, S; Rabbani, M; Mahzouni, P; Afsharipour, M; Minaiyan, M

    2012-07-01

    Trinitrobenzene sulfonic acid (TNBS)-induced colitis is one of the most common methods for studying inflammatory bowel disease in animal models. Several factors may, however, affect its reproducibility, rate of animal mortality, and macroscopic and histopathological outcomes. Our aim was to validate the main contributing factors to this method and compare the effects of different reference drugs upon remission of resultant colon injuries. TNBS was dissolved in 0.25 ml of ethanol (50% v/v) and instilled (25, 50, 100 and 150 mg/kg) intracolonically to the male Wistar rats. After determination of optimum dose of TNBS in male rats and assessment of this dose in female rats, they were treated with reference drugs including dexamethasone [1 mg/kg, intraperitoneally (i.p.) and 2 mg/kg, orally (p.o.)], Asacol (mesalazine, 100 mg/kg, p.o.; 150 mg/kg, enema) and hydrocortisone acetate (20 mg/kg, i.p.; 20 mg/kg, enema) which started 2 h after colitis induction and continued daily for 6 consecutive days. Thereafter, macroscopic and microscopic parameters and clinical features were assessed and compared in different groups. We found that the optimum dose of TNBS for the reproducibility of colonic damage with the least mortality rate was 50 mg/kg. Amongst studied reference drugs, hydrocortisone acetate (i.p.), dexamethasone (i.p. and p.o.) and Asacol (p.o.) significantly diminished the severity of macroscopic and microscopic injuries and could be considered effective for experimental colitis studies in rats . Our findings suggest that optimization of TNBS dose is essential for induction of colitis under the laboratory conditions; and gender exerts no impact upon macroscopic and histological characteristics of TNBS-induced colitis in rats. Furthermore, the enema forms of hydrocortisone and Asacol are not appropriate reference drugs. PMID:23181094

  16. Adiponectin and plant-derived mammalian adiponectin homolog exert a protective effect in murine colitis

    KAUST Repository

    Arsenescu, Violeta

    2011-04-11

    Background: Hypoadiponectinemia has been associated with states of chronic inflammation in humans. Mesenteric fat hypertrophy and low adiponectin have been described in patients with Crohn\\'s disease. We investigated whether adiponectin and the plant-derived homolog, osmotin, are beneficial in a murine model of colitis. Methods: C57BL/6 mice were injected (i.v.) with an adenoviral construct encoding the full-length murine adiponectin gene (AN+DSS) or a reporter-LacZ (Ctr and V+DSS groups) prior to DSS colitis protocol. In another experiment, mice with DSS colitis received either osmotin (Osm+DSS) or saline (DSS) via osmotic pumps. Disease progression and severity were evaluated using body weight, stool consistency, rectal bleeding, colon lengths, and histology. In vitro experiments were carried out in bone marrow-derived dendritic cells. Results: Mice overexpressing adiponectin had lower expression of proinflammatory cytokines (TNF, IL-1β), adipokines (angiotensin, osteopontin), and cellular stress and apoptosis markers. These mice had higher levels of IL-10, alternative macrophage marker, arginase 1, and leukoprotease inhibitor. The plant adiponectin homolog osmotin similarly improved colitis outcome and induced robust IL-10 secretion. LPS induced a state of adiponectin resistance in dendritic cells that was reversed by treatment with PPARγ agonist and retinoic acid. Conclusion: Adiponectin exerted protective effects during murine DSS colitis. It had a broad activity that encompassed cytokines, chemotactic factors as well as processes that assure cell viability during stressful conditions. Reducing adiponectin resistance or using plant-derived adiponectin homologs may become therapeutic options in inflammatory bowel disease. © 2011 Springer Science+Business Media, LLC.

  17. Anti-inflammatory and anti-oxidant activities of olmesartan medoxomil ameliorate experimental colitis in rats

    Energy Technology Data Exchange (ETDEWEB)

    Nagib, Marwa M. [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Misr International University, Cairo (Egypt); Tadros, Mariane G., E-mail: mirogeogo@yahoo.com [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo (Egypt); ELSayed, Moushira I. [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Misr International University, Cairo (Egypt); Khalifa, Amani E. [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo (Egypt)

    2013-08-15

    Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) driven through altered immune responses with production of proinflammatory cytokines. Many therapies are used, but side effects and loss of response limit long-term effectiveness. New therapeutic strategies are thus needed for patients who don't respond to current treatments. Recently, there is suggested involvement of the proinflammatory hormone angiotensin II in inflammatory bowel disease. The aim of this study was to investigate the possible role of olmesartan medoxomil (OLM-M), an angiotensin II receptor blocker in ameliorating ulcerative colitis. Colitis was induced in male Wistar rats by administration of 5% dextran sodium sulphate (DSS) in drinking water for 5 days. OLM-M (1, 3 and 10 mg/kg) was administered orally during 21 days prior to the induction of colitis, and for 5 days after. Sulfasalazine (500 mg/kg) was used as reference drug. All animals were tested for changes in colon length, disease activity index (DAI) and microscopic damage. Colon tissue concentration/activity of tumor necrosis alpha (TNF-α), myeloperoxidase (MPO), prostaglandin E2 (PGE2), reduced glutathione (GSH) and malondialdehyde (MDA) were assessed. Results showed that the OLM-M dose-dependently ameliorated the colonic histopathological and biochemical injuries, an effect that is comparable or even better than that of the standard sulfasalazine. These results suggest that olmesartan medoxomil may be effective in the treatment of UC through its anti-inflammatory and antioxidant effects. - Highlights: • Olmesartan medoximil reduced dextran sodium sulphate- induced colitis. • Mechanism involved anti-inflammatory and antioxidant effects dose- dependently. • It suppressed malondialdehyde and restored reduced glutathione levels. • It reduced inflammatory markers levels and histological changes.

  18. Lipid alterations in experimental murine colitis: role of ceramide and imipramine for matrix metalloproteinase-1 expression.

    Directory of Open Access Journals (Sweden)

    Jessica Bauer

    Full Text Available BACKGROUND: Dietary lipids or pharmacologic modulation of lipid metabolism are potential therapeutic strategies in inflammatory bowel disease (IBD. Therefore, we analysed alterations of bioactive lipids in experimental models of colitis and examined the functional consequence of the second messenger ceramide in inflammatory pathways leading to tissue destruction. METHODOLOGY/PRINCIPAL FINDINGS: Chronic colitis was induced by dextran-sulphate-sodium (DSS or transfer of CD4(+CD62L(+ cells into RAG1(-/--mice. Lipid content of isolated murine intestinal epithelial cells (IEC was analysed by tandem mass spectrometry. Concentrations of MMP-1 in supernatants of Caco-2-IEC and human intestinal fibroblasts from patients with ulcerative colitis were determined by ELISA. Imipramine was used for pharmacologic inhibition of acid sphingomyelinase (ASM. Ceramide increased by 71% in chronic DSS-induced colitis and by 159% in the transfer model of colitis. Lysophosphatidylcholine (LPC decreased by 22% in both models. No changes were detected for phosphatidylcholine. Generation of ceramide by exogenous SMase increased MMP-1-protein production of Caco-2-IEC up to 7-fold. Inhibition of ASM completely abolished the induction of MMP-1 by TNF or IL-1beta in Caco-2-IEC and human intestinal fibroblasts. CONCLUSIONS/SIGNIFICANCE: Mucosal inflammation leads to accumulation of ceramide and decrease of LPC in the intestinal epithelium. One aspect of ceramide generation is an increase of MMP-1. Induction of MMP-1 by TNF or IL-1beta is completely blocked by inhibition of ASM with imipramine. Therefore, inhibition of ASM may offer a treatment strategy to reduce MMP-1 expression and tissue destruction in inflammatory conditions.

  19. The ROS-generating oxidase Nox1 is required for epithelial restitution following colitis.

    Science.gov (United States)

    Kato, Masayoshi; Marumo, Masaya; Nakayama, Jun; Matsumoto, Misaki; Yabe-Nishimura, Chihiro; Kamata, Tohru

    2016-07-29

    Accumulating evidence suggests that reactive oxygen species (ROS) generated by endogenous metabolic enzymes are involved in a variety of intracellular mechanisms. In particular, superoxide-generating NADPH oxidase (Nox) 1 is highly expressed in the colon and has been implicated in physiological and pathophysiological states of colon tissues. However, its role in tissue repair following colitis has not been fully elucidated. Our study using experimental colitis in mice showed that repair of the mucosal layer did not occur in Nox1-deficient mice following dextran sulfate sodium-induced colitis. This was accompanied by inhibition of proliferation, cell survival, migration, and terminal differentiation (generation of goblet cells) of crypt progenitor cells, as determined by histochemical analyses. Furthermore, Nox1 expression as well as ROS production in the colon crypt was increased during the repair process, and Nox1 deficiency suppressed these events. The results suggest that Nox1 promotes colon mucosal wound repair by sustaining the bioactivity of crypt progenitor cells and plays a crucial role in the epithelial restitution in the case of damage associated with colitis. PMID:26876598

  20. Anti-TNF-refractory colitis after checkpoint inhibitor therapy: Possible role of CMV-mediated immunopathogenesis.

    Science.gov (United States)

    Lankes, Katharina; Hundorfean, Gheorghe; Harrer, Thomas; Pommer, Ansgar J; Agaimy, Abbas; Angelovska, Irena; Tajmir-Riahi, Azadeh; Göhl, Jonas; Schuler, Gerold; Neurath, Markus F; Hohenberger, Werner; Heinzerling, Lucie

    2016-06-01

    Immune-related adverse events (irAEs) induced by checkpoint inhibitors are well known. Since fatal outcomes have been reported early detection and adequate management are crucial. In particular, colitis is frequently observed and can result in intestinal perforation. This is the first report of an autoimmune colitis that was treated according to algorithms but became resistant due to a CMV reactivation. The 32-y-old male patient with metastatic melanoma treated within an anti-PD-1/ipilimumab combination study developed severe immune-mediated colitis (CTCAE grade 3) with up to 18 watery stools per day starting 2 weeks after treatment initiation. After improving upon therapy with immunosuppressive treatment (high dose steroids and infliximab) combined with parenteral nutrition diarrhea again exacerbated. Additionally, the patient had asymptomatic grade 3 CTCAE amylase and lipase elevation. Colitis was monitored by weekly endoscopies and colon biopsies were analyzed histologically with CMV staining, multi-epitope ligand cartography (MELC) and qRT-PCR for inflammatory genes. In the course, CMV reactivation was detected in the colon and treated with antiviral medication in parallel to a reduction of corticosteroids. Subsequently, symptoms improved. The patient showed a complete response for 2 y now including regression of bone metastases. CMV reactivation under checkpoint inhibitor therapy in combination with immunosuppressive treatment for autoimmune side effects has to be considered in these patients and if present treated. Potentially, CMV reactivation is underdiagnosed. Treatment algorithms should include CMV diagnostics. PMID:27471608

  1. Highly specific blockade of CCR5 inhibits leukocyte trafficking and reduces mucosal inflammation in murine colitis.

    Science.gov (United States)

    Mencarelli, Andrea; Cipriani, Sabrina; Francisci, Daniela; Santucci, Luca; Baldelli, Franco; Distrutti, Eleonora; Fiorucci, Stefano

    2016-08-05

    Targeted disruption of leukocyte trafficking to the gut represents a promising approach for the treatment of inflammatory bowel diseases (IBDs). CCR5, the shared receptor for MIP1α and β and RANTES, is expressed by multiple leukocytes. Here, we aimed to determine the role of CCR5 in mediating leukocyte trafficking in models of colitis, and evaluate the therapeutic potential of maraviroc, an orally active CCR5 antagonist used in the treatment of CCR5-tropic HIV. Acute and chronic colitis were induced by administration of DSS or TNBS to wild-type and CCR5(-/-) mice or adoptive transfer of splenic naïve CD4(+) T-cells from wild type or CCR5(-/-) mice into RAG-1(-/-). CCR5 gene ablation reduced the mucosal recruitment and activation of CCR5-bearing CD4(+) and CD11b(+) leukocytes, resulting in profound attenuation of signs and symptoms of inflammation in the TNBS and transfer models of colitis. In the DSS/TNBS colitis and in the transfer model, maraviroc attenuated development of intestinal inflammation by selectively reducing the recruitment of CCR5 bearing leukocytes. In summary, CCR5 regulates recruitment of blood leukocytes into the colon indicating that targeting CCR5 may offer therapeutic options in IBDs.

  2. Anti-inflammatory effects of nicotine in obesity and ulcerative colitis

    Directory of Open Access Journals (Sweden)

    Kirchgessner Annette

    2011-08-01

    Full Text Available Abstract Cigarette smoke is a major risk factor for a number of diseases including lung cancer and respiratory infections. Paradoxically, it also contains nicotine, an anti-inflammatory alkaloid. There is increasing evidence that smokers have a lower incidence of some inflammatory diseases, including ulcerative colitis, and the protective effect involves the activation of a cholinergic anti-inflammatory pathway that requires the α7 nicotinic acetylcholine receptor (α7nAChR on immune cells. Obesity is characterized by chronic low-grade inflammation, which contributes to insulin resistance. Nicotine significantly improves glucose homeostasis and insulin sensitivity in genetically obese and diet-induced obese mice, which is associated with suppressed adipose tissue inflammation. Inflammation that results in disruption of the epithelial barrier is a hallmark of inflammatory bowel disease, and nicotine is protective in ulcerative colitis. This article summarizes current evidence for the anti-inflammatory effects of nicotine in obesity and ulcerative colitis. Selective agonists for the α7nAChR could represent a promising pharmacological strategy for the treatment of inflammation in obesity and ulcerative colitis. Nevertheless, we should keep in mind that the anti-inflammatory effects of nicotine could be mediated via the expression of several nAChRs on a particular target cell.

  3. Mutagenic efficiency of radiations and chemical mutagens in inducing viable mutations in rice

    International Nuclear Information System (INIS)

    Studies were undertaken to compare the effectiveness and efficiency of radiations (gamma rays and fast neutrons) and chemical mutagens (EMS and NMU) in inducing viable mutations in rice. Radiations were more effective than chemical mutagens, the most effective being fast neutrons. Mutagenic efficiency when estimated on the basis of lethality was higher for radiations but when based on sterility was higher for chemical mutagens. Fast neutrons, more effective than gamma rays, were less efficient. NMU was more effective but less efficient than EMS. (author)

  4. Mechanisms of the hepatoprotective effects of tamoxifen against drug-induced and chemical-induced acute liver injuries

    Energy Technology Data Exchange (ETDEWEB)

    Yoshikawa, Yukitaka; Miyashita, Taishi; Higuchi, Satonori [Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920‐1192 (Japan); Tsuneyama, Koichi [Department of Diagnostic Pathology, Graduate School of Medicine and Pharmaceutical Science for Research, University of Toyama, Sugitani, Toyama 930‐0194 (Japan); Endo, Shinya [Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920‐1192 (Japan); Tsukui, Tohru [Research Center for Genomic Medicine, Saitama Medical University, Yamane, Hidaka 350‐1241 (Japan); Toyoda, Yasuyuki; Fukami, Tatsuki; Nakajima, Miki [Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920‐1192 (Japan); Yokoi, Tsuyoshi, E-mail: tyokoi@p.kanazawa-u.ac.jp [Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920‐1192 (Japan)

    2012-10-01

    Although estrogen receptor (ER)α agonists, such as estradiol and ethinylestradiol (EE2), cause cholestasis in mice, they also reduce the degree of liver injury caused by hepatotoxicants as well as ischemia–reperfusion. The functional mechanisms of ERα have yet to be elucidated in drug-induced or chemical-induced liver injury. The present study investigated the effects of an ERα agonist, selective ER modulators (SERMs) and an ER antagonist on drug-induced and chemical-induced liver injuries caused by acetaminophen, bromobenzene, diclofenac, and thioacetamide (TA). We observed hepatoprotective effects of EE2, tamoxifen (TAM) and raloxifene pretreatment in female mice that were exposed to a variety of hepatotoxic compounds. In contrast, the ER antagonist did not show any hepatoprotective effects. DNA microarray analyses suggested that monocyte to macrophage differentiation-associated 2 (Mmd2) protein, which has an unknown function, is commonly increased by TAM and RAL pretreatment, but not by pretreatment with the ER antagonist. In ERα-knockout mice, the hepatoprotective effects of TAM and the increased expression of Mmd2 mRNA were not observed in TA-induced liver injury. To investigate the function of Mmd2, the expression level of Mmd2 mRNA was significantly knocked down to approximately 30% in mice by injection of siRNA for Mmd2 (siMmd2). Mmd2 knockdown resulted in a reduction of the protective effects of TAM on TA-induced liver injury in mice. This is the first report of the involvement of ERα in drug-induced or chemical-induced liver injury. Upregulation of Mmd2 protein in the liver was suggested as the mechanism of the hepatoprotective effects of EE2 and SERMs. -- Highlights: ► Liver injury induced by drugs or chemicals was investigated in mice. ► Liver injury was suppressed by pretreatment with tamoxifen in female mice. ► Mmd2, whose function was unknown, could be a candidate gene for liver protection. ► Tamoxifen up-regulated Mmd2 mRNA expression

  5. Golimumab for the treatment of ulcerative colitis

    NARCIS (Netherlands)

    Lowenberg, M.; Boer, N. de; Hoentjen, F.

    2014-01-01

    The introduction of therapeutic antibodies against tumor necrosis factor (TNF) had a major impact on the treatment of ulcerative colitis (UC). Infliximab and adalimumab are powerful agents that are used for remission induction and maintenance therapy in UC and have an acceptable safety profile. Howe

  6. Colitis following fecal diversion: still a challenge

    Directory of Open Access Journals (Sweden)

    Castro Leonaldson dos Santos

    2000-01-01

    Full Text Available After fecal diversion, nonspecific colitis may be seen in the defunctionalized colon. The purpose of this prospective study is to identify specific findings that could help in the differential diagnosis between diversion colitis and other inflammatory bowel diseases in order to avoid inappropriate diagnosis and therapy. It was studied, prospectively, thirteen consecutive patients from two public hospitals of Rio de Janeiro who had undergone temporary colostomy for indications other than inflammatory bowel disease. They were submitted to endoscopy with biopsy of both proximal and distal colorectal segments, and prospectively evaluated before and after restoration of intestinal continuity. Endoscopy with biopsy of both proximal and distal excluded colorectal segments showed a nonspecific mucosal and submucosal inflammation, resembling ulcerative colitis ( p < 0.01. There was endoscopic resolution in all patients once restoration of intestinal continuity was established (p < 0.01 and also histologic improvement after the stoma closure. In conclusion there are no specific findings that make possible an unequivocal distinction between diversion colitis and other nonspecific inflammatory diseases. Diagnosis should be achieved if after stoma closure occur remission of endoscopic large bowel inflammatory signs with improvement in mucosal histologic appearance and prompt relief of clinical complaints.

  7. Selenoprotein P in colitis-associated carcinoma

    Science.gov (United States)

    Short, Sarah P.; Whitten-Barrett, Caitlyn; Williams, Christopher S.

    2016-01-01

    ABSTRACT Patients with inflammatory bowel disease are often deficient in micronutrients such as selenium and have an increased risk of colon cancer. We tested whether the selenium transport protein, selenoprotein P, could modify colitis-associated cancer. Our results indicate that global SEPP1 haploinsufficiency augments tumorigenesis and mediates oxidative damage in the intestine. PMID:27314080

  8. Cerebral Arterial Thrombosis in Ulcerative Colitis

    Directory of Open Access Journals (Sweden)

    Giovanni Casella

    2013-01-01

    Full Text Available Thrombosis, mainly venous, is a rare and well-recognized extraintestinal manifestation of inflammatory bowel disease (IBD. We describe a 25-year-old Caucasian man affected by ulcerative colitis and sclerosing cholangitis with an episode of right middle cerebral arterial thrombosis resolved by intraarterial thrombolysis. We perform a brief review of the International Literature.

  9. Ulcerative colitis flare with splenic ven thrombosis.

    Science.gov (United States)

    Bozkurt, Huseyin Sancar; Kara, Banu; Citil, Serdal

    2015-01-01

    Patients with ulcerative colitis (UC) have an increased risk of thromboembolic events. Here, we present a 28-year-old man with active ulcerative pancolitis presenting via splenic vein thrombosis and left renal superior infarct that was not associated with a surgical procedure.

  10. Neutrophil Extracellular Traps in Ulcerative Colitis

    DEFF Research Database (Denmark)

    Bennike, Tue Bjerg; Carlsen, Thomas Gelsing; Ellingsen, Torkell;

    2015-01-01

    BACKGROUND: The etiology of the inflammatory bowel diseases, including ulcerative colitis (UC), remains incompletely explained. We hypothesized that an analysis of the UC colon proteome could reveal novel insights into the disease etiology. METHODS: Mucosal colon biopsies were taken by endoscopy...

  11. Small-bowel permeability in collagenous colitis

    DEFF Research Database (Denmark)

    Wildt, Signe; Madsen, Jan L; Rumessen, Jüri J

    2006-01-01

    Collagenous colitis (CC) is a chronic inflammatory bowel disease that affects the colon. However, some patients with CC present with accompanying pathologic small-bowel manifestations such as coeliac disease, defects in bile acid absorption and histopathologic changes in small-intestinal biopsies...

  12. Manipulation of enteric flora in ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Mario Guslandi

    2005-01-01

    @@ TO THE EDITOR Reviewing the available therapeutic options in the medical treatment of ulcerative colitis, Xu et al.[1], have omitted to mention an important aspect in the pharmacological management of the disease, namely the possibility to promote clinical and endoscopic improvement by manipulating the enteric flora.

  13. Microarray Assisted Gene Discovery in Ulcerative Colitis

    DEFF Research Database (Denmark)

    Brusgaard, Klaus

    Inflammatory Bowel disease (IBD) is a condition characterised by chronic recidivous inflammation of the bowel and intestine. IBD includes chron´s disease (CD) and ulcerative colitis (UC). The combined prevalence of CD and UC are app. 1 in 500 in the general Caucasian population. In 25% of the cases...

  14. Chemical chaperone 4-phenylbutyrate prevents endoplasmic reticulum stress induced by T17M rhodopsin

    OpenAIRE

    Jiang, Haibo; Xiong, Siqi; Xia, Xiaobo

    2014-01-01

    Background Rhodopsin mutations are associated with the autosomal dominant form of retinitis pigmentosa. T17M mutation in rhodopsin predisposes cells to endoplasmic reticulum (ER) stress and induces cell death. This study aimed to examine whether chemical chaperone 4-phenylbutyrate prevents ER stress induced by rhodopsin T17M. Results ARPE-19 cells were transfected with myc-tagged wild-type (WT) and T17M rhodopsin constructs. Turnover of WT and T17M rhodopsin was measured by cycloheximide chas...

  15. Physico-chemical study of the focused electron beam induced deposition process

    OpenAIRE

    Bret, Tristan; Hoffmann, Patrik

    2007-01-01

    The focused electron beam induced deposition process is a promising technique for nano and micro patterning. Electrons can be focused in sub-angström dimensions, which allows atomic-scale resolution imaging, analysis, and processing techniques. Before the process can be used in controlled applications, the precise nature of the deposition mechanism must be described and modelled. The aim of this research work is to present a physical and chemical description of the focused electron beam induc...

  16. Juvenile ferric iron prevents microbiota dysbiosis and colitis in adult rodents

    Institute of Scientific and Technical Information of China (English)

    Chourouk Ettreiki; Pascale Gadonna-Widehem; Irène Mangin; Mo(i)se Co(e)ffier; Carine Delayre-Orthez; Pauline M Anton

    2012-01-01

    AIM:To assess whether juvenile chronic ferric iron ingestion limit colitis and dysbiosis at adulthood in rats and mice.METHODS:Two sets of experiments were designed.In the first set,recently weaned mice were either orally administered ferrous (Fe2+) iron salt or ferric (Fe3+) microencapsulated iron for 6 wk.The last week of experiments trinitrobenzene sulfonic acid (TNBS) colitis was induced.In the second set,juvenile rats received the microencapsulated ferric iron for 6 wk and were also submitted to TNBS colitis during the last week of experiments.In both sets of experiments,animals were sacrificed 7 d after TNBS instillation.Severity of the inflammation was assessed by scoring macroscopic lesions and quantifying colonic myeloperoxidase (MPO) activity.Alteration of the microflora profile was estimated using quantitative polymerase chain reaction (qPCR) by measuring the evolution of total caecal microflora,Bacteroidetes,Firmicutes and enterobacteria.RESULTS:Neither ferrous nor ferric iron daily exposures at the juvenile period result in any effect in control animals at adulthood although ferrous iron repeated administration in infancy limited weight gain.Ferrous iron was unable to limit the experimental colitis (1.71 ± 0.27MPO U/mg protein vs 2.47 ± 0.22 MPO U/mg protein in colitic mice).In contrast,ferric iron significantly prevented the increase of MPO activity (1.64 ± 0.14 MPO U/mg protein) in TNBS-induced colitis.Moreover,this positive effect was observed at both the doses of ferric iron used (75 and 150 mg/kg per day po-6 wk).In the study we also compared,in both rats and mice,the consequences of chronic repeated low level exposure to ferric iron (75 mg/kg per day po-6 wk) on TNBS-induced colitis and its related dysbiosis.We confirmed that ferric iron limited the TNBS-induced increase of MPO activity in both the rodent species.Furthermore,we assessed the ferric iron incidence on TNBS-induced intestinal microbiota dysbiosis.At first,we needed to optimize the

  17. Force-induced chemical reactions on the metal centre in a single metalloprotein molecule

    Science.gov (United States)

    Zheng, Peng; Arantes, Guilherme M.; Field, Martin J.; Li, Hongbin

    2015-06-01

    Metalloproteins play indispensable roles in biology owing to the versatile chemical reactivity of metal centres. However, studying their reactivity in many metalloproteins is challenging, as protein three-dimensional structure encloses labile metal centres, thus limiting their access to reactants and impeding direct measurements. Here we demonstrate the use of single-molecule atomic force microscopy to induce partial unfolding to expose metal centres in metalloproteins to aqueous solution, thus allowing for studying their chemical reactivity in aqueous solution for the first time. As a proof-of-principle, we demonstrate two chemical reactions for the FeS4 centre in rubredoxin: electrophilic protonation and nucleophilic ligand substitution. Our results show that protonation and ligand substitution result in mechanical destabilization of the FeS4 centre. Quantum chemical calculations corroborated experimental results and revealed detailed reaction mechanisms. We anticipate that this novel approach will provide insights into chemical reactivity of metal centres in metalloproteins under biologically more relevant conditions.

  18. 思密达治疗溃疡性结肠炎腹泻的机制和疗效%Mechanisms and Therapeutic Effects of Smecta in Treating Diarrhea Induced by Ulcerative Colitis

    Institute of Scientific and Technical Information of China (English)

    江学良; 崔慧斐; 任晶

    2011-01-01

    目的 探讨思密达治疗溃疡性结肠炎腹泻的机制和疗效.方法 选取成年Wistar大鼠80只,用二硝基氯苯(DNCB)和乙酸(AA)复合法造模成功后1周随机分为2组,每组40只.美沙拉嗪治疗组(对照组)大鼠喂服美沙拉嗪0.2 g·kg-1·d-1,8周;思密达联合美沙拉嗪治疗组(联合治疗组)大鼠喂服美沙拉嗪0.2 g·kg-1·d-1,天然蒙脱石0.6 g·kg-1·d-1,治疗8周.分别在治疗前和治疗后记录腹泻症状变化,测定肠道黏膜通透性[以尿中乳果糖(L)/甘露醇(M)的比值表示],光镜下观察结肠组织学变化,电镜下观察肠黏膜超微结构包括微绒毛变化、组织紧密连接、上皮细胞间隙、肠基底膜细胞核分裂相和细胞凋亡情况.结果 与对照组比较,联合治疗组大鼠腹泻次数恢复正常时间[(9.9±4.8)d]及黏液脓血便消失时间[(11.6±6.2)d]较对照组[(15.8±3.2)d和(16.6±3.7)d]显著缩短,差异有统计学意义(P<0.05);肠黏膜通透性[(28.6±4.2)%]较对照组[(35.6±4.7)%]显著降低(P<0.05);肠黏膜组织学缓解明显(P<0.05),超微结构恢复正常时间[(35.8±6.2)d]较对照组[(52.0±8.7)d]显著缩短(P<0.05).结论 思密达联合美沙拉嗪治疗溃疡性结肠炎,可以通过修复损伤肠黏膜屏障,降低肠黏膜通透性,从而快速缓解腹泻症状.%Objective To investigate the mechanisms and therapeutic effects of Smecta in treating diarrhea induced by Ulcerative Colitis.Methods Eighty adult Wistar rats were randomized into 2 groups ( 40 each ) 1 week after establishment of the model using dinitrochlorobenzol ( DNCB ) combined with hawkinsin.Animals were administered with Mesalazine ( 0.2 g ? kg-1 ? d ) in the control group and Mesalazine ( 0.2 g ? kg-1 ? d-1 ) combined with Smecta ( 0.6 g ? kg-1 ? d-1 ) in the combined treatment group for 8 weeks.Diarrhoea status before and after treatment were recorded.Entero - membrane permeability ( lactu-lose admannitol in urine ) was determined

  19. Lymphocytic colitis: A clue to bacterial etiology

    Institute of Scientific and Technical Information of China (English)

    Thanaa EA Helal; Naglaa S Ahmed; Osama Abo El Fotoh

    2005-01-01

    AIM: To find out the role of bacteria as a possible etiological factor in lymphocytic colitis.METHODS: Twenty patients with histopathological diagnosis of lymphocytic colitis and 10 normal controls were included in this study. Colonoscopic biopsies were obtained from three sites (hepatic and splenic flexures and rectosigmoid region). Each biopsy was divided into two parts. A fresh part was incubated on special cultures for bacterial growth. The other part was used for the preparation of histologic tissue sections that were examined for the presence of bacteria with the help of Giemsa stain.RESULTS: Culture of tissue biopsies revealed bacterial growth in 18 out of 20 patients with lymphocytic colitis mostly Escherichia coli(14/18), which was found in all rectosigmoid specimens (14/14), but only in 8/14 and 6/14 of splenic and hepatic flexure specimens respectively. In two of these cases, E coliwas associated with proteus. Proteus was found only in one case, Klebsiella in two cases, and Staphylococcus aureus in one case. In the control group, only 2 out of 10 controls showed the growth of E coliin their biopsy cultures.Histopathology showed rod-shaped bacilli in the tissue sections of 12 out of 14 cases with positive E coliin their specimen's culture. None of the controls showed these bacteria in histopathological sections.CONCLUSION: This preliminary study reports an association between E coliand lymphocytic colitis, based on histological and culture observations. Serotyping and molecular studies are in process to assess the role of E coliin the pathogenesis of lymphocytic colitis.

  20. Effects of garlicin on apoptosis in rat model of colitis

    Institute of Scientific and Technical Information of China (English)

    Xi-Ming Xu; Jie-Ping Yu; Xiao-Fei He; Jun-Hua Li; Liang-Liang Yu; Hong-Gang Yu

    2005-01-01

    AIM: To investigate the effects of garlicin on apoptosis and expression of bcl-2 and bax in lymphocytes in rat model of ulcerative colitis (UC).METHODS: Healthy adult Sprague-Dawley rats of both sexes, weighing 180±30 g, were employed in the present study. The rat model of UC was induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) enema. The experimental animals were randomly divided into garlicin treatment group (including high and low concentration), model control group, and normal control group. Rats in garlicin treatment group and model control group received intracolic garlicin daily at doses of 10.0 and 30.0 mg/kg and equal amount of saline respectively 24 h after colitis model was induced by alcohol and TNBS co-enema. Rats in normal control group received neither alcohol nor only TNBS but only saline enema in this study. On the 28th d of the experiment, rats were executed, the expression of bcl-2 and bax protein was determined immunohistochemically and the apoptotic cells were detected by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate fluorescence nick end labeling (TUNEL) method. At the same time, the rat colon mucosal damage index (CMDI) was calculated.RESULTS: In garlicin treatment group, the positive expression of bcl-2 in lymphocytes decreased and the number of apoptotic cells was more than that in model control group, CMDI was lower than that in model control group. The posi