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Sample records for experimental colitis mediated

  1. Therapeutic effect of curcumin on experimental colitis mediated by inhibiting CD8+CD11c+ cells.

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    Zhao, Hai-Mei; Han, Fei; Xu, Rong; Huang, Xiao-Ying; Cheng, Shao-Min; Huang, Min-Fang; Yue, Hai-Yang; Wang, Xin; Zou, Yong; Xu, Han-Lin; Liu, Duan-Yong

    2017-03-14

    To verify whether curcumin (Cur) can treat inflammatory bowel disease by regulating CD8+CD11c+ cells. We evaluated the suppressive effect of Cur on CD8+CD11c+ cells in spleen and Peyer's patches (PPs) in colitis induced by trinitrobenzene sulfonic acid. Mice with colitis were treated by 200 mg/kg Cur for 7 d. On day 8, the therapeutic effect of Cur was evaluated by visual assessment and histological examination, while co-stimulatory molecules of CD8+CD11c+ cells in the spleen and PPs were measured by flow cytometry. The levels of interleukin (IL)-10, interferon (IFN)-γ and transforming growth factor (TGF)-β1 in spleen and colonic mucosa were determined by ELISA. The disease activity index, colon weight, weight index of colon and histological score of experimental colitis were obviously decreased after Cur treatment, while the body weight and colon length recovered. After treatment with Cur, CD8+CD11c+ cells were decreased in the spleen and PPs, and the expression of major histocompatibility complex II, CD205, CD40, CD40L and intercellular adhesion molecule-1 was inhibited. IL-10, IFN-γ and TGF-β1 levels were increased compared with those in mice with untreated colitis. Cur can effectively treat experimental colitis, which is realized by inhibiting CD8+CD11c+ cells.

  2. Xilei San Ameliorates Experimental Colitis in Rats by Selectively Degrading Proinflammatory Mediators and Promoting Mucosal Repair

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    Yongbiao Hao

    2014-01-01

    Full Text Available Xilei san (XLS, a herbal preparation widely used in China for erosive and ulcerative diseases, has been shown to be effective in ulcerative colitis (UC. The present experiments were conducted to assess its efficacy and determine its mechanism of action in a rat model that resembles human UC. The model was induced by adding 4% dextran sulfate sodium (DSS to the rats’ drinking water for 7 days. XLS was administered daily by retention enema from day 2 to day 7; the rats were sacrificed on day 8. The colon tissues were obtained for further experiments. A histological damage score and the activity of tissue myeloperoxidase were used to evaluate the severity of the colitis. The colonic cytokine levels were detected in a suspension array, and epithelial proliferation was assessed using Ki-67 immunohistochemistry. Intrarectal administration of XLS attenuated the DSS-induced colitis, as evidenced by a reduction in both the histological damage score and myeloperoxidase activity. It also decreased the levels of proinflammatory cytokines, but increased the mucosal repair-related cytokines. In addition, the epithelial Ki-67 expression was upregulated by XLS. These results suggest that XLS attenuates DSS-induced colitis by degrading proinflammatory mediators and promoting mucosal repair. XLS could be a potential topical treatment for human UC.

  3. Protective effect of marine mangrove Rhizophora apiculata on acetic acid induced experimental colitis by regulating anti-oxidant enzymes, inflammatory mediators and nuclear factor-kappa B subunits.

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    V, Vinod Prabhu; C, Guruvayoorappan

    2014-01-01

    Ulcerative colitis is a disease that causes inflammation and ulcer in the lining of the large intestine. In this study we investigate the effect of Rhizophora apiculata (R. apiculata) on acetic acid induced colitis in mouse model. Experimental animals were randomized into four groups: normal untreated, colitis control, R. apiculata treated group and sulfasalazine treated group. R. apiculata significantly (p<0.01) decreased macroscopic score and wet weight of damaged colon compared to colitis control. This effect was confirmed biochemically by significant (p<0.01) reduction of colitis associated increase in myeloperoxidase activity. R. apiculata significantly (p<0.05) increased anti-oxidant enzymes such as superoxide dismutase (SOD) and glutathione (GSH) levels compared to colitis control. R. apiculata significantly (p<0.01) reduced lipid peroxides (LPO), nitric oxide (NO) and inflammatory mediators such as myeloperoxidase (MPO), lactate dehydrogenase (LDH), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and tumor necrosis factor-α (TNF-α) expressions compared to colitis control. R. apiculata treatment significantly (p<0.01) inhibits the translocation of NF-kB p65 and p50 subunits. Taken together these findings suggest that R. apiculata prevents acetic acid induced colitis in experimental mouse model and may serve as an excellent anti-oxidant and anti-inflammatory agent that could potentially be useful as a (natural) therapy for inflammatory bowel disease (IBD). Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Downregulation of CX3CR1 ameliorates experimental colitis: evidence for CX3CL1-CX3CR1-mediated immune cell recruitment.

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    Becker, Felix; Holthoff, Christina; Anthoni, Christoph; Rijcken, Emile; Alexander, J Steven; Gavins, Felicity N E; Spiegel, H U; Senninger, Norbert; Vowinkel, Thorsten

    2017-03-01

    Inflammatory conditions like inflammatory bowel diseases (IBD) are characterized by increased immune cell infiltration. The chemokine ligand CX3CL1 and its receptor CX3CR1 have been shown to be involved in leukocyte adhesion, transendothelial recruitment, and chemotaxis. Therefore, the objective of this study was to describe CX3CL1-CX3CR1-mediated signaling in the induction of immune cell recruitment during experimental murine colitis. Acute colitis was induced by dextran sodium sulfate (DSS), and sepsis was induced by injection of lipopolysaccharide (LPS). Serum concentrations of CX3CR1 and CX3CL1 were measured by ELISA. Wild-type and CX3CR1-/- mice were challenged with DSS, and on day 6, intravital microscopy was performed to monitor colonic leukocyte and platelet recruitment. Intestinal inflammation was assessed by disease activity, histopathology, and neutrophil infiltration. CX3CR1 was upregulated in DSS colitis and LPS-induced sepsis. CX3CR1-/- mice were protected from disease severity and intestinal injury in DSS colitis, and CX3CR1 deficiency resulted in reduced rolling of leukocytes and platelets. In the present study, we provide evidence for a crucial role of CX3CL1-CX3CR1 in experimental colitis, in particular for intestinal leukocyte recruitment during murine colitis. Our findings suggest that CX3CR1 blockade represents a potential therapeutic strategy for treatment of IBD.

  5. IL-22 Restrains Tapeworm-Mediated Protection against Experimental Colitis via Regulation of IL-25 Expression.

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    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.

  6. Ceramide-CD300f binding suppresses experimental colitis by inhibiting ATP-mediated mast cell activation

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    Matsukawa, Toshihiro; Izawa, Kumi; Isobe, Masamichi; Takahashi, Mariko; Maehara, Akie; Yamanishi, Yoshinori; Kaitani, Ayako; Okumura, Ko; Teshima, Takanori; Kitamura, Toshio; Kitaura, Jiro

    2016-01-01

    Objective Extracellular ATP mediates mast cell-dependent intestinal inflammation via P2X7 purinoceptors. We have previously shown that CD300f (also called the leucocyte mono-immunoglobulin-like receptor 3 (LMIR3)) suppresses immunoglobulin E-dependent and mast cell-dependent allergic responses by binding to ceramide. The aim of the present study was to clarify the role of ceramide–LMIR3 interaction in the development of IBD. Design The dextran sodium sulfate (DSS)-induced colitis model was used in wild-type (WT), LMIR3−/−, mast cell-deficient KitW-sh/W-sh, KitW-sh/W-shLMIR3−/− or KitW-sh/W-sh mice engrafted with WT or LMIR3−/− bone marrow-derived mast cells (BMMCs). The severity of colitis was determined by clinical and histological criteria. Lamina propria cell populations were assessed by flow cytometry. Production of chemical mediators from lamina propria cells was measured by real-time reverse transcription PCR. Production of chemical mediators from ATP-stimulated BMMCs in the presence or absence of ceramide was measured by ELISA. The severity of DSS-induced colitis was assessed in mice given either an Fc fusion protein containing an extracellular domain of LMIR3, and anticeramide antibody, or ceramide liposomes. Results LMIR3 deficiency exacerbated DSS-induced colitis in mice. KitW-sh/W-sh mice harbouring LMIR3−/− mast cells exhibited more severe colitis than those harbouring WT mast cells. Ceramide–LMIR3 interaction inhibited ATP-stimulated activation of BMMCs. DSS-induced colitis was aggravated by disrupting the ceramide–LMIR3 interaction, whereas it was suppressed by treating with ceramide liposomes. Conclusions LMIR3-deficient colonic mast cells were pivotal in the exacerbation of DSS-induced colitis in LMIR3−/− mice. Ceramide liposomes attenuated DSS-induced colitis by inhibiting ATP-mediated activation of colonic mast cells through ceraimide–LMIR3 binding. PMID:25673319

  7. Epithelial EZH2 serves as an epigenetic determinant in experimental colitis by inhibiting TNFα-mediated inflammation and apoptosis.

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    Liu, Yongfeng; Peng, Junjie; Sun, Tongyu; Li, Ni; Zhang, Le; Ren, Jiale; Yuan, Huairui; Kan, Shan; Pan, Qiang; Li, Xiang; Ding, Yufeng; Jiang, Min; Cong, Xiaoji; Tan, Minjia; Ma, Yushui; Fu, Da; Cai, Sanjun; Xiao, Yichuan; Wang, Xiaoming; Qin, Jun

    2017-05-09

    Epithelial barrier disruption is a major cause of inflammatory bowel disease (IBD); however, the mechanism through which epigenetic regulation modulates intestinal epithelial integrity remains largely undefined. Here we show that EZH2, the catalytic subunit of polycomb repressive complex (PRC2), is indispensable for maintaining epithelial cell barrier integrity and homeostasis under inflammatory conditions. In accordance with reduced EZH2 expression in patients, the inactivation of EZH2 in IECs sensitizes mice to DSS- and TNBS-induced experimental colitis. Conversely, EZH2 overexpression in the intestinal epithelium renders mice more resistant to colitis. Mechanistically, the genes encoding TRAF2/5 are held in a finely tuned bivalent status under inflammatory conditions. EZH2 deficiency potentiates the expression of these genes to enhance TNFα-induced NF-κB signaling, thereby leading to uncontrolled inflammation. More importantly, we show that EZH2 depletion compromises the protective role of NF-κB signaling in cell survival by directly up-regulating ITCH, a well-known E3 ligase that degrades the c-FLIP protein. Thus, our findings highlight an epigenetic mechanism by which EZH2 integrates the multifaceted effects of TNFα signaling to promote the inflammatory response and apoptosis in colitis.

  8. RNase-L deficiency exacerbates experimental colitis and colitis-associated cancer

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    Long, Tiha M.; ArindamChakrabarti; Ezelle, Heather J.; E. Brennan-Laun, Sarah; Raufman, Jean-Pierre; Polyakova, Irina; H. Silverman, Robert; Hassel, Bret A.

    2013-01-01

    Background The endoribonuclease RNase-L is a type-I interferon (IFN)-regulatedcomponent of the innate immune response that functions in antiviral, antibacterial and antiproliferative activities. RNase-L produces RNA agonists of RIG-I-like receptors (RLRs), sensors of cytosolic pathogen-associated RNAs that induce cytokines including IFNβ. IFNβ and RLR signaling mediate protective responses against experimental colitis and colitis-associated cancer (CAC) and contribute to gastrointestinal (GI) homeostasis. Therefore, we investigated a role for RNase-L in murine colitis and CAC and its association with RLR signaling in response to bacterial RNA. Methods Colitis was induced in wild type (WT) and RNase-L-deficient mice (RNase-L−/−) by administration of dextran sulphate sodium (DSS). CAC was induced by DSS and azoxymethane (AOM). Histological analysis and immunohistochemistry were performed on colon tissue to analyze immune cell infiltration and tissue damage following induction of colitis. Expression of cytokines was measured by qRT-PCR and ELISA. Results DSS-treated RNase-L−/− mice exhibited a significantly higher clinical score, delayed leukocyte infiltration, reduced expression of IFNβ, TNFα, IL-1β and IL-18at early times post-DSS exposure and increased mortalityas compared to WT mice. DSS/AOM-treated RNase-L−/−mice displayed an increased tumor burden. Bacterial RNA triggeredIFNβproductionin an RNase-L-dependent manner and provided a potential mechanism by whichRNase-L contributes to the GI immune response to microbiota and protects against experimental colitis and CAC. Conclusions RNase-L promotes the innate immune response to intestinal damage and ameliorates murine colitis and CAC. The RNase-L-dependent production of IFNβ stimulated by bacterial RNA may be a mechanism to protectagainst GI inflammatory disease. PMID:23567782

  9. Dietary Salt Exacerbates Experimental Colitis.

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    Tubbs, Alan L; Liu, Bo; Rogers, Troy D; Sartor, R Balfour; Miao, Edward A

    2017-08-01

    The Western diet is characterized by high protein, sugar, fat, and low fiber intake, and is widely believed to contribute to the incidence and pathogenesis of inflammatory bowel disease (IBD). However, high sodium chloride salt content, a defining feature of processed foods, has not been considered as a possible environmental factor that might drive IBD. We set out to bridge this gap. We examined murine models of colitis on either a high salt diet (HSD) or a low salt diet. We demonstrate that an HSD exacerbates inflammatory pathology in the IL-10-deficient murine model of colitis relative to mice fed a low salt diet. This was correlated with enhanced expression of numerous proinflammatory cytokines. Surprisingly, sodium accumulated in the colons of mice on an HSD, suggesting a direct effect of salt within the colon. Similar to the IL-10-deficient model, an HSD also enhanced cytokine expression during infection by Salmonella typhimurium This occurred in the first 3 d of infection, suggesting that an HSD potentiates an innate immune response. Indeed, in cultured dendritic cells we found that high salt media potentiates cytokine expression downstream of TLR4 activation via p38 MAPK and SGK1. A third common colitis model, administration of dextran sodium sulfate, was hopelessly confounded by the high sodium content of the dextran sodium sulfate. Our results raise the possibility that high dietary salt is an environmental factor that drives increased inflammation in IBD. Copyright © 2017 by The American Association of Immunologists, Inc.

  10. Heme oxygenase-1-generated biliverdin ameliorates experimental murine colitis.

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    Berberat, Pascal O; A-Rahim, Yousif I; Yamashita, Kenichiro; Warny, Michel M; Csizmadia, Eva; Robson, Simon C; Bach, Fritz H

    2005-04-01

    Heme oxygenase-1 (HO-1) seems to have an important protective role in acute and chronic inflammation. The products of heme catalysis, biliverdin/bilirubin, carbon monoxide (CO), and iron (that induces apoferritin) mediate the beneficial effects of HO-1. Blockade of HO-1 activity results in exacerbation of experimental colitis. We tested whether HO-1 has protective effects in the development of colitis and determined that specific enzymatic products of HO-1 are responsible for these effects. Colitis was induced by oral administration of dextran sodium sulfate (5%) to C57BL/6 mice for 7 days. HO-1 was up-regulated by cobalt-protoporphyrin (5 mg/kg, intraperitoneally). Biliverdin, exogenous CO, or the iron chelator desferrioxamine was administered to other groups. Cobalt-protoporphyrin treatment resulted in significant up-regulation of HO-1 protein in mucosal and submucosal cells. Induction of HO-1 was associated with significantly less loss of body weight in mice with induced colitis (-12% versus -22% in the control animals, P biliverdin administration (50 micromol/kg, 3 times per day, intraperitoneally). We conclude that heightened HO-1 expression or administration of biliverdin ameliorates dextran sodium sulfate-induced experimental colitis. Novel therapeutic strategies based on HO-1 and/or biliverdin administration may have use in inflammatory bowel disease.

  11. Disruption of Tumor Necrosis Factor Receptor-Associated Factor 5 Exacerbates Murine Experimental Colitis via Regulating T Helper Cell-Mediated Inflammation.

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    Shang, Jian; Li, Lixia; Wang, Xiaobing; Pan, Huaqin; Liu, Shi; He, Ruohang; Li, Jin; Zhao, Qiu

    2016-01-01

    Tumor necrosis factor (TNF) receptor-associated factor 5 (TRAF5) is a key mediator of TNF receptor superfamily members and is important in both T helper (Th) cell immunity and the regulation of multiple signaling pathways. To clarify TRAF5's influence on inflammatory bowel diseases (IBDs), we investigated TRAF5 deficiency's effect on dextran sulfate sodium- (DSS-) induced colitis. Colitis was induced in TRAF5 knockout (KO) mice and their wild-type (WT) littermates by administering 3% DSS orally for 7 days. The mice were then sacrificed, and their colons were removed. Our data suggested that KO mice were more susceptible to DSS-induced colitis. TRAF5 deficiency significantly enhanced IFN-γ, IL-4, and IL-17a mRNA and protein levels in the colons of DSS-fed mice, and the mRNA expression of T-bet and GATA-3 was also markedly elevated. However, ROR-α and ROR-γt mRNA levels did not differ between DSS-induced KO and WT mice. Flow cytometry showed increased frequencies of Th2 and IFN-γ/IL-17a-coproducing CD4(+) T cells in the colons of DSS-induced KO mice. Additionally, TRAF5 deficiency significantly enhanced the activation of NF-κB in CD4(+) T cells after DSS administration. These results indicated that TRAF5 deficiency significantly aggravated DSS-induced colitis, most likely by regulating Th cell-mediated inflammation.

  12. Disruption of Tumor Necrosis Factor Receptor-Associated Factor 5 Exacerbates Murine Experimental Colitis via Regulating T Helper Cell-Mediated Inflammation

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    Jian Shang

    2016-01-01

    Full Text Available Tumor necrosis factor (TNF receptor-associated factor 5 (TRAF5 is a key mediator of TNF receptor superfamily members and is important in both T helper (Th cell immunity and the regulation of multiple signaling pathways. To clarify TRAF5’s influence on inflammatory bowel diseases (IBDs, we investigated TRAF5 deficiency’s effect on dextran sulfate sodium- (DSS- induced colitis. Colitis was induced in TRAF5 knockout (KO mice and their wild-type (WT littermates by administering 3% DSS orally for 7 days. The mice were then sacrificed, and their colons were removed. Our data suggested that KO mice were more susceptible to DSS-induced colitis. TRAF5 deficiency significantly enhanced IFN-γ, IL-4, and IL-17a mRNA and protein levels in the colons of DSS-fed mice, and the mRNA expression of T-bet and GATA-3 was also markedly elevated. However, ROR-α and ROR-γt mRNA levels did not differ between DSS-induced KO and WT mice. Flow cytometry showed increased frequencies of Th2 and IFN-γ/IL-17a-coproducing CD4+ T cells in the colons of DSS-induced KO mice. Additionally, TRAF5 deficiency significantly enhanced the activation of NF-κB in CD4+ T cells after DSS administration. These results indicated that TRAF5 deficiency significantly aggravated DSS-induced colitis, most likely by regulating Th cell-mediated inflammation.

  13. Bergenin, Acting as an Agonist of PPARγ, Ameliorates Experimental Colitis in Mice through Improving Expression of SIRT1, and Therefore Inhibiting NF-κB-Mediated Macrophage Activation

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    Kai Wang

    2018-01-01

    Full Text Available Bergenin, isolated from the herb of Saxifraga stolonifera Curt. (Hu-Er-Cao, has anti-inflammatory, antitussive and wound healing activities. The aim of the present study was to identify the effect of bergenin on experimental colitis, and explored the related mechanisms. Our results showed that oral administration of bergenin remarkably alleviated disease symptoms of mice with dextran sulfate sodium (DSS-induced colitis, evidenced by reduced DAI scores, shortening of colon length, MPO activity and pathologic abnormalities in colons. Bergenin obviously inhibited the mRNA and protein expressions of IL-6 and TNF-α in colon tissues, but not that of mucosal barrier-associated proteins occludin, E-cadherin and MUC-2. In vitro, bergenin significantly inhibited the expressions of IL-6 and TNF-α as well as nuclear translocation and DNA binding activity of NF-κB-p65 in lipopolysaccharide (LPS-stimulated peritoneal macrophages and RAW264.7 cells, which was almost reversed by addition of PPARγ antagonist GW9662 and siPPARγ. Subsequently, bergenin was identified as a PPARγ agonist. It could enter into macrophages, bind with PPARγ, promote nuclear translocation and transcriptional activity of PPARγ, and increase mRNA expressions of CD36, LPL and ap2. In addition, bergenin significantly up-regulated expression of SIRT1, inhibited acetylation of NF-κB-p65 and increased association NF-κB-p65 and IκBα. Finally, the correlation between activation of PPARγ and attenuation of colitis, inhibition of IL-6 and TNF-α expressions, NF-κB-p65 acetylation and nuclear translocation, and up-regulation of SIRT1 expression by bergenin was validated in mice with DSS-induced colitis and/or LPS-stimulated macrophages. In summary, bergenin could ameliorate colitis in mice through inhibiting the activation of macrophages via regulating PPARγ/SIRT1/NF-κB-p65 pathway. The findings can provide evidence for the further development of bergenin as an anti-UC drug, and

  14. Salvinorin A has antiinflammatory and antinociceptive effects in experimental models of colitis in mice mediated by KOR and CB1 receptors.

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    Fichna, Jakub; Dicay, Michael; Lewellyn, Kevin; Janecka, Anna; Zjawiony, Jordan K; MacNaughton, Wallace K; Storr, Martin A

    2012-06-01

    Salvinorin A (SA) has a potent inhibitory action on mouse gastrointestinal (GI) motility and ion transport, mediated primarily by kappa-opioid receptors (KOR). The aim of the present study was to characterize possible antiinflammatory and antinociceptive effects of SA in the GI tract of mice. Colonic damage scores and myeloperoxidase activity were determined after intraperitoneal (i.p.), intracolonic (i.c.), and oral (p.o.) administration of SA using the trinitrobenzene sulfonic acid (TNBS) and dextran sodium sulfate (DSS) models of colitis in mice. Additionally, KOR, cannabinoid (CB)1, and CB2 western blot analysis of colon samples was performed. The antinociceptive effect of SA was examined based on the number of behavioral responses to i.c. instillation of mustard oil (MO). The i.p. (3 mg/kg, twice daily) and p.o. (10 mg/kg, twice daily) administration of SA significantly attenuated TNBS and DSS colitis in mice. The effect of SA was blocked by KOR antagonist nor-binaltorphimine (10 mg/kg, i.p.). Western blot analysis showed no influence of SA on KOR, CB1, or CB2 levels. SA (3 mg/kg, i.p. and 10 mg/kg, i.c.) significantly decreased the number of pain responses after i.c. instillation of MO in the vehicle- and TNBS-treated mice. The antinociceptive action of SA was blocked by KOR and CB1 antagonists. The analgesic effect of i.c. SA was more potent in TNBS-treated mice compared to controls. Our results suggest that the drugs based on the structure of SA have the potential to become valuable antiinflammatory or analgesic therapeutics for the treatment of GI diseases. Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.

  15. Different Subsets of Enteric Bacteria Induce and Perpetuate Experimental Colitis in Rats and Mice

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    Rath, Heiko C.; Schultz, Michael; Freitag, René; Dieleman, Levinus A.; Li, Fengling; Linde, Hans-Jörg; Schölmerich, Jürgen; Sartor, R. Balfour

    2001-01-01

    Resident bacteria are incriminated in the pathogenesis of experimental colitis and inflammatory bowel diseases. We investigated the relative roles of various enteric bacteria populations in the induction and perpetuation of experimental colitis. HLA-B27 transgenic rats received antibiotics (ciprofloxacin, metronidazole, or vancomycin-imipenem) in drinking water or water alone in either prevention or treatment protocols. Mice were treated similarly with metronidazole or vancomycin-imipenem before or after receiving 5% dextran sodium sulfate (DSS). Germfree transgenic rats were colonized with specific-pathogen-free enteric bacteria grown overnight either in anaerobic or aerobic atmospheres. Nontransgenic rats colonized with anaerobic bacteria served as negative controls. Although preventive metronidazole significantly attenuated colitis in transgenic rats and DSS-treated mice, it had no therapeutic benefit once colitis was established. Ciprofloxacin also partially prevented but did not treat colitis in B27 transgenic rats. In both animal models vancomycin-imipenem most effectively prevented and treated colitis. Germfree transgenic rats reconstituted with enteric bacteria grown under anaerobic conditions had more aggressive colitis than those associated with aerobic bacteria. These results suggest that a subset of resident luminal bacteria induces colitis, but that a complex interaction of commensal aerobic and anaerobic bacteria provides the constant antigenic drive for chronic immune-mediated colonic inflammation. PMID:11254584

  16. B cells exposed to enterobacterial components suppress development of experimental colitis

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    Schmidt, Esben Gjerløff Wedebye; Larsen, Hjalte List; Kristensen, Nanna Ny

    2012-01-01

    ). RESULTS: We demonstrate that splenic B cells exposed to ebx produce large amounts of IL-10 in vitro and express CD1d and CD5 previously known to be associated with regulatory B cells. In SCID mice transplanted with colitogenic CD4(+) CD25(-) T cells, co-transfer of ebx-B cells significantly suppressed...... development of colitis. Suppression was dependent on B cell-derived IL-10, as co-transfer of IL-10 knockout ebx-B cells failed to suppress colitis. Ebx-B cell-mediated suppression of colitis was associated with a decrease in interferon gamma (IFN-¿)-producing T(H) 1 cells and increased frequencies of Foxp3......-expressing T cells. CONCLUSIONS: These data demonstrate that splenic B cells exposed to enterobacterial components acquire immunosuppressive functions by which they can suppress development of experimental T cell-mediated colitis in an IL-10-dependent way. (Inflamm Bowel Dis 2011;)....

  17. Sex Differences in Experimentally Induced Colitis in Mice: a Role for Estrogens.

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    Bábíčková, Janka; Tóthová, Ľubomíra; Lengyelová, Eva; Bartoňová, Anastázie; Hodosy, Július; Gardlík, Roman; Celec, Peter

    2015-10-01

    Sex differences have been found in the incidence and progression of inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn's disease. The reported differences in observational studies are controversial, and the effects of sex hormones on the pathogenesis of IBD are not clear. The aim of this study was to analyze sex differences in the progression of experimentally induced colitis. Experimental colitis was induced in adult mice by adding 2% dextran sodium sulfate (DSS) into drinking water. Male and female mice were used as intact, gonadectomized, and supplemented with either estradiol or testosterone. In comparison to males, female mice with induced colitis had significantly longer colon (p < 0.05), lower decrease in body weight (p < 0.001), and lower stool consistency score (p < 0.05). Histopathological analysis showed less inflammatory infiltrates (p < 0.001) and crypt damage (p < 0.001) in female mice. Female mice with colitis had also lower concentration of TNF-α in colon homogenates (p < 0.01). Supplementation with estradiol in ovariectomized mice ameliorated the severity of colitis. Female mice are partially protected against chemically induced colitis. This protection seems to be mediated by estradiol.

  18. Preventive and therapeutic euphol treatment attenuates experimental colitis in mice.

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    Rafael C Dutra

    Full Text Available BACKGROUND: The tetracyclic triterpene euphol is the main constituent found in the sap of Euphorbia tirucalli. This plant is widely known in Brazilian traditional medicine for its use in the treatment of several kinds of cancer, including leukaemia, prostate and breast cancers. Here, we investigated the effect of euphol on experimental models of colitis and the underlying mechanisms involved in its action. METHODOLOGY/PRINCIPAL FINDINGS: Colitis was induced in mice either with dextran sulfate sodium (DSS or with 2,4,6-trinitrobenzene sulfonic acid (TNBS, and the effect of euphol (3, 10 and 30 mg/kg on colonic injury was assessed. Pro-inflammatory mediators and cytokines were measured by immunohistochemistry, enzyme-Linked immunoabsorbent assay (ELISA, real time-polymerase chain reaction (RT-PCR and flow cytometry. Preventive and therapeutic oral administration of euphol attenuated both DSS- and TNBS-induced acute colitis as observed by a significant reduction of the disease activity index (DAI, histological/microscopic damage score and myeloperoxidase (MPO activity in colonic tissue. Likewise, euphol treatment also inhibited colon tissue levels and expression of IL-1β, CXCL1/KC, MCP-1, MIP-2, TNF-α and IL-6, while reducing NOS2, VEGF and Ki67 expression in colonic tissue. This action seems to be likely associated with inhibition of activation of nuclear factor-κB (NF-κB. In addition, euphol decreased LPS-induced MCP-1, TNF-α, IL-6 and IFN-γ, but increased IL-10 secretion from bone marrow-derived macrophages in vitro. Of note, euphol, at the same schedule of treatment, markedly inhibited both selectin (P- and E-selectin and integrin (ICAM-1, VCAM-1 and LFA-1 expression in colonic tissue. CONCLUSIONS/SIGNIFICANCE: Together, these results clearly demonstrated that orally-administered euphol, both preventive or therapeutic treatment were effective in reducing the severity of colitis in two models of chemically-induced mouse colitis and suggest

  19. Preventive and Therapeutic Euphol Treatment Attenuates Experimental Colitis in Mice

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    Bento, Allisson F.; Marcon, Rodrigo; Schmidt, Éder C.; Bouzon, Zenilda L.; Pianowski, Luiz F.; Calixto, João B.

    2011-01-01

    Background The tetracyclic triterpene euphol is the main constituent found in the sap of Euphorbia tirucalli. This plant is widely known in Brazilian traditional medicine for its use in the treatment of several kinds of cancer, including leukaemia, prostate and breast cancers. Here, we investigated the effect of euphol on experimental models of colitis and the underlying mechanisms involved in its action. Methodology/Principal Findings Colitis was induced in mice either with dextran sulfate sodium (DSS) or with 2,4,6-trinitrobenzene sulfonic acid (TNBS), and the effect of euphol (3, 10 and 30 mg/kg) on colonic injury was assessed. Pro-inflammatory mediators and cytokines were measured by immunohistochemistry, enzyme-Linked immunoabsorbent assay (ELISA), real time-polymerase chain reaction (RT-PCR) and flow cytometry. Preventive and therapeutic oral administration of euphol attenuated both DSS- and TNBS-induced acute colitis as observed by a significant reduction of the disease activity index (DAI), histological/microscopic damage score and myeloperoxidase (MPO) activity in colonic tissue. Likewise, euphol treatment also inhibited colon tissue levels and expression of IL-1β, CXCL1/KC, MCP-1, MIP-2, TNF-α and IL-6, while reducing NOS2, VEGF and Ki67 expression in colonic tissue. This action seems to be likely associated with inhibition of activation of nuclear factor-κB (NF-κB). In addition, euphol decreased LPS-induced MCP-1, TNF-α, IL-6 and IFN-γ, but increased IL-10 secretion from bone marrow-derived macrophages in vitro. Of note, euphol, at the same schedule of treatment, markedly inhibited both selectin (P- and E-selectin) and integrin (ICAM-1, VCAM-1 and LFA-1) expression in colonic tissue. Conclusions/Significance Together, these results clearly demonstrated that orally-administered euphol, both preventive or therapeutic treatment were effective in reducing the severity of colitis in two models of chemically-induced mouse colitis and suggest this plant

  20. Colitis

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    ... this page: //medlineplus.gov/ency/article/001125.htm Colitis To use the sharing features on this page, please enable JavaScript. Colitis is swelling (inflammation) of the large intestine (colon). ...

  1. Increased permeability to polyethylene glycol 4000 in rabbits with experimental colitis

    Energy Technology Data Exchange (ETDEWEB)

    Seidman, E.G.; Hanson, D.G.; Walker, W.A.

    1986-01-01

    Little information is available regarding colonic permeability to macromolecules in health or disease states. In vivo permeability of rabbit colon to (/sup 14/C)polyethylene glycol 4000 (/sup 14/C-PEG) was examined in the presence of immune complex-mediated experimental colitis and compared with that of partially treated (control) and normal rabbits. Permeability was assessed by urinary /sup 14/C-PEG excretion after intrarectal administration of 0.1 mM solution of /sup 14/C-PEG (1 ml/kg, 7.5 X 10(6) cpm/ml). Experimental colitis greatly increased colonic permeability (p less than 0.001 in two-way analysis of variance) compared with control and normal groups (2.06% +/- 0.19%, 0.14% +/- 0.04%, and 0.01% +/- 0.004%, respectively, of rectally administered counts). Gel diffusion chromatography showed that absorbed /sup 14/C-PEG was excreted into urine unchanged, demonstrating its applicability as an inert, nonmetabolizable macromolecular probe. Urinary clearance after mesenteric vein administration of /sup 14/C-PEG was similar in normal animals and animals with colitis, implicating colonic absorption as the source of the group differences. Postmortem histology confirmed the acute colitis lesions in the experimental group. These findings support the hypothesis that nonspecific colonic inflammation is associated with significant alterations of mucosal permeability.

  2. Interleukin-7 receptor blockade suppresses adaptive and innate inflammatory responses in experimental colitis

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    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

  3. Ixeris dentata NAKAI Reduces Clinical Score and HIF-1 Expression in Experimental Colitis in Mice

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    Dae-Seung Kim

    2013-01-01

    Full Text Available Ixeris dentata (ID is an herbal medicine used in Asian countries to treat indigestion, pneumonia, hepatitis, contusions, and tumors; however, its effect on intestinal inflammation is unknown. Thus, we investigated the effect of ID in the dextran sulfate sodium (DSS model of colitis in female BALB/c mice; animals were evaluated after seven days of DSS treatment. DSS-treated mice showed considerable clinical signs, including weight loss, reduced colon length, colonic epithelial injury, infiltration of inflammatory cells in the colon tissue, and upregulation of inflammatory mediators. However, administration of ID attenuated body weight loss, colon shortening, and the increase in disease activity index score. ID also significantly decreased the colonic mucosal injury and the number of infiltrating mast cells. Moreover, ID inhibited the expressions of cyclooxygenase-2 and hypoxia-inducible factor-1α in colon tissue. Taken together, the results provide experimental evidence that ID might be a useful therapy for patients with ulcerative colitis.

  4. Ixeris dentata NAKAI Reduces Clinical Score and HIF-1 Expression in Experimental Colitis in Mice

    Science.gov (United States)

    Ko, Jang-Ho; Jeon, Yong-Deok; Han, Yo-Han; Kim, Hyun-Ju; Poudel, Amrit; Jung, Hyun-Ju; Ku, Sae-Kwang; Kim, Su-Jin; Park, Sang-Hyun; Choi, Byung-Min; Park, Sung-Joo; Um, Jae-Young; Hong, Seung-Heon

    2013-01-01

    Ixeris dentata (ID) is an herbal medicine used in Asian countries to treat indigestion, pneumonia, hepatitis, contusions, and tumors; however, its effect on intestinal inflammation is unknown. Thus, we investigated the effect of ID in the dextran sulfate sodium (DSS) model of colitis in female BALB/c mice; animals were evaluated after seven days of DSS treatment. DSS-treated mice showed considerable clinical signs, including weight loss, reduced colon length, colonic epithelial injury, infiltration of inflammatory cells in the colon tissue, and upregulation of inflammatory mediators. However, administration of ID attenuated body weight loss, colon shortening, and the increase in disease activity index score. ID also significantly decreased the colonic mucosal injury and the number of infiltrating mast cells. Moreover, ID inhibited the expressions of cyclooxygenase-2 and hypoxia-inducible factor-1α in colon tissue. Taken together, the results provide experimental evidence that ID might be a useful therapy for patients with ulcerative colitis. PMID:24194783

  5. Fibroblast Growth Factor 21 Deficiency Attenuates Experimental Colitis-Induced Adipose Tissue Lipolysis

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    Liming Liu

    2017-01-01

    Full Text Available Aims. Nutrient deficiencies are common in patients with inflammatory bowel disease (IBD. Adipose tissue plays a critical role in regulating energy balance. Fibroblast growth factor 21 (FGF21 is an important endocrine metabolic regulator with emerging beneficial roles in lipid homeostasis. We investigated the impact of FGF21 in experimental colitis-induced epididymal white adipose tissue (eWAT lipolysis. Methods. Mice were given 2.5% dextran sulfate sodium (DSS ad libitum for 7 days to induce colitis. The role of FGF21 was investigated using antibody neutralization or knockout (KO mice. Lipolysis index and adipose lipolytic enzymes were determined. In addition, 3T3-L1 cells were pretreated with IL-6, followed by recombinant human FGF21 (rhFGF21 treatment; lipolysis was assessed. Results. DSS markedly decreased eWAT/body weight ratio and increased serum concentrations of free fatty acid (FFA and glycerol, indicating increased adipose tissue lipolysis. eWAT intracellular lipolytic enzyme expression/activation was significantly increased. These alterations were significantly attenuated in FGF21 KO mice and by circulating FGF21 neutralization. Moreover, DSS treatment markedly increased serum IL-6 and FGF21 levels. IL-6 pretreatment was necessary for the stimulatory effect of FGF21 on adipose lipolysis in 3T3-L1 cells. Conclusions. Our results demonstrate that experimental colitis induces eWAT lipolysis via an IL-6/FGF21-mediated signaling pathway.

  6. Dimethyl Fumarate Reduces Inflammatory Responses in Experimental Colitis

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    Casili, Giovanna; Cordaro, Marika; Impellizzeri, Daniela; Bruschetta, Giuseppe; Paterniti, Irene; Cuzzocrea, Salvatore

    2016-01-01

    Background and Aims: Fumaric acid esters have been proven to be effective for the systemic treatment of psoriasis and multiple sclerosis. We aimed to develop a new treatment for colitis. Methods: We investigated the effect of dimethylfumarate [DMF, 10-30-100mg/kg] on an experimental model of colitis induced by dinitrobenzene sulphuric acid [DNBS]. We also evaluated the therapeutic activity of 7 weeks’ treatment with DMF [30mg/kg] on 9-week-old IL-10KO mice that spontaneously develop a T helper-1 [Th1]-dependent chronic enterocolitis after birth, that is fully established at 8–10 weeks of age. The mechanism of this pharmacological potential of DMF [10 μM] was investigated in colonic epithelial cell monolayers [Caco-2] exposed to H2O2. The barrier function was evaluated by the tight junction proteins. Results: The treatment with DMF significantly reduced the degree of haemorrhagic diarrhoea and weight loss caused by administration of DNBS. DMF [30 and 100mg/kg] also caused a substantial reduction in the degree of colon injury, in the rise in myeloperoxidase [MPO] activity, and in the increase in tumour necrosis factor [TNF]-α expression, as well as in the up-regulation of ICAM-1 caused by DNBS in the colon. Molecular studies demonstrated that DMF impaired NF-κB signalling via reduced p65 nuclear translocalisation. DMF induced a stronger antioxidant response as evidenced by a higher expression of Mn-superoxide dismutase. Moreover, DMF protected human intestinal epithelial cells against H2O2-induced barrier dysfunction, restoring ZO-1 occludin expression, via the HO-1 pathway. Conclusions: DMF treatment reduces the degree of colitis caused by DNBS. We propose that DMF treatment may be useful in the treatment of inflammatory bowel disease. PMID:26690241

  7. Genetic deletion of dectin-1 does not affect the course of murine experimental colitis

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    Heinsbroek Sigrid EM

    2012-04-01

    Full Text Available Abstract Background It is believed that inflammatory bowel diseases (IBD result from an imbalance in the intestinal immune response towards the luminal microbiome. Dectin-1 is a widely expressed pattern recognition receptor that recognizes fungi and upon recognition it mediates cytokine responses and skewing of the adaptive immune system. Hence, dectin-1 may be involved in the pathogenesis of IBD. Methods We assessed the responses of dectin-1 deficient macrophages to the intestinal microbiota and determined the course of acute DSS and chronic Helicobacter hepaticus induced colitis in dectin-1 deficient mice. Results We show that the mouse intestinal microbiota contains fungi and the cytokine responses towards this microbiota were significantly reduced in dectin-1 deficient macrophages. However, in two different colitis models no significant differences in the course of inflammation were found in dectin-1 deficient mice compared to wild type mice. Conclusions Together our data suggest that, although at the immune cell level there is a difference in response towards the intestinal flora in dectin-1 deficient macrophages, during intestinal inflammation this response seems to be redundant since dectin-1 deficiency in mice does not affect intestinal inflammation in experimental colitis.

  8. Nanoparticle curcumin ameliorates experimental colitis via modulation of gut microbiota and induction of regulatory T cells.

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    Masashi Ohno

    Full Text Available Curcumin is a hydrophobic polyphenol derived from turmeric, a traditional Indian spice. Curcumin exhibits various biological functions, but its clinical application is limited due to its poor absorbability after oral administration. A newly developed nanoparticle curcumin shows improved absorbability in vivo. In this study, we examined the effects of nanoparticle curcumin (named Theracurmin on experimental colitis in mice.BALB/c mice were fed with 3% dextran sulfate sodium (DSS in water. Mucosal cytokine expression and lymphocyte subpopulation were analyzed by real-time PCR and flow cytometry, respectively. The profile of the gut microbiota was analyzed by real-time PCR.Treatment with nanoparticle curcumin significantly attenuated body weight loss, disease activity index, histological colitis score and significantly improved mucosal permeability. Immunoblot analysis showed that NF-κB activation in colonic epithelial cells was significantly suppressed by treatment with nanoparticle curcumin. Mucosal mRNA expression of inflammatory mediators was significantly suppressed by treatment with nanoparticle curcumin. Treatment with nanoparticle curcumin increased the abundance of butyrate-producing bacteria and fecal butyrate level. This was accompanied by increased expansion of CD4+ Foxp3+ regulatory T cells and CD103+ CD8α- regulatory dendritic cells in the colonic mucosa.Treatment with nanoparticle curcumin suppressed the development of DSS-induced colitis potentially via modulation of gut microbial structure. These responses were associated with induction of mucosal immune cells with regulatory properties. Nanoparticle curcumin is one of the promising candidates as a therapeutic option for the treatment of IBD.

  9. Effect of appendicectomy on colonic inflammation and neoplasia in experimental ulcerative colitis.

    Science.gov (United States)

    Harnoy, Y; Bouhnik, Y; Gault, N; Maggiori, L; Sulpice, L; Cazals-Hatem, D; Boudjema, K; Panis, Y; Ogier-Denis, E; Treton, X

    2016-10-01

    Ulcerative colitis (UC) promotes cancer, and can be ameliorated by early appendicectomy for appendicitis. The aim of the study was to explore the effect of appendicectomy on colitis and colonic neoplasia in an animal model of colitis and a cohort of patients with UC. Five-week old IL10/Nox1(DKO) mice with nascent colitis and 8-week-old IL10/Nox1(DKO) mice with established colitis underwent appendicectomy (for experimental appendicitis or no appendicitis) or sham laparotomy. The severity and extent of colitis was assessed by histopathological examination, and a clinical disease activity score was given. From a cohort of consecutive patients with UC who underwent colectomy, the prevalence of appendicectomy and pathological findings were collected from two institutional databases. Appendicectomy for appendicitis ameliorated experimental colitis in the mice; the effect was more pronounced in the 5-week-old animals. Appendicectomy in the no-appendicitis group was associated with an increased rate of colonic high-grade dysplasia (HGD) or cancer compared with rates in sham and appendicitis groups (13 of 20 versus 0 of 20 and 0 of 20 respectively; P neoplasia (odds ratio 16·88, 95 per cent c.i. 3·32 to 112·69). Appendicectomy for experimental appendicitis ameliorated colitis. The risk of colorectal neoplasia appeared to increase following appendicectomy without induced appendicitis in a mouse model of colitis, and in patients with UC who had undergone appendicectomy. Surgical relevance Appendicectomy for appendicitis protects against UC. In this murine model of colitis, appendicectomy for experimental appendicitis protected against colitis, but appendicectomy without appendicitis promoted colorectal carcinogenesis. In patients with ulcerative colitis who underwent colectomy, absence of the appendix (proof of previous appendicectomy) in the resection specimen was independently associated with colorectal neoplasia. Although patients with UC and a history of

  10. Ghrelin ameliorates intestinal barrier dysfunction in experimental colitis by inhibiting the activation of nuclear factor-kappa B

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    Cheng, Jian; Zhang, Lin [Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai (China); Dai, Weiqi [Department of Gastroenterology, Shanghai Tenth People' s Hospital, Tongji University, Shanghai (China); Mao, Yuqing [Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai (China); Li, Sainan [Department of Gastroenterology, Shanghai Tenth People' s Hospital, Tongji University, Shanghai (China); Wang, Jingjie; Li, Huanqing [Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai (China); Guo, Chuanyong [Department of Gastroenterology, Shanghai Tenth People' s Hospital, Tongji University, Shanghai (China); Fan, Xiaoming, E-mail: xiaomingfan57@sina.com [Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai (China)

    2015-02-27

    Aim: This study aimed to investigate the effect and underlying mechanism of ghrelin on intestinal barrier dysfunction in dextran sulfate sodium (DSS)-induced colitis. Methods and results: Acute colitis was induced in C57BL/6J mice by administering 2.5% DSS. Saline or 25, 125, 250 μg/kg ghrelin was administrated intraperitoneally (IP) to mice 1 day before colitis induction and on days 4, 5, and 6 after DSS administration. IP injection of a ghrelin receptor antagonist, [D-lys{sup 3}]-GHRP-6, was performed immediately prior to ghrelin injection. Ghrelin (125 or 250 μg/kg) could reduce the disease activity index, histological score, and myeloperoxidase activities in experimental colitis, and also prevented shortening of the colon. Ghrelin could prevent the reduction of transepithelial electrical resistance and tight junction expression, and bolstered tight junction structural integrity and regulated cytokine secretion. Ultimately, ghrelin inhibited nuclear factor kappa B (NF-κB), inhibitory κB-α, myosin light chain kinase, and phosphorylated myosin light chain 2 activation. Conclusions: Ghrelin prevented the breakdown of intestinal barrier function in DSS-induced colitis. The protective effects of ghrelin on intestinal barrier function were mediated by its receptor GHSR-1a. The inhibition of NF-κB activation might be part of the mechanism underlying the effects of ghrelin that protect against barrier dysfunction. - Highlights: • Ghrelin ameliorates intestinal barrier dysfunction in experimental colitis. • The effect of ghrelin is mediated by GHSR-1a. • Inhibition of NF-κB activation.

  11. Experimental colitis delays and reduces the severity of collagen-induced arthritis in mice.

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    Hablot, Julie; Peyrin-Biroulet, Laurent; Kokten, Tunay; El Omar, Reine; Netter, Patrick; Bastien, Claire; Jouzeau, Jean-Yves; Sokol, Harry; Moulin, David

    2017-01-01

    Amongst extraintestinal manifestations (EIM) occurring in IBD patients, rheumatologic manifestations are the most frequent. Understanding the relationships between arthritis and colitis is a prerequisite to improving the management of these patients. Microbiota of patients with IBD or rheumatologic diseases, like spondyloarthritis (SpA) is modified compared to healthy individual. Thus, we have evaluated the impact of colitis in the development of arthritis in mice and we have analyzed microbiota changes. Collagen-induced arthritis (CIA) was induced at day 0 in DBA1 mice exposed or not to Dextran Sodium Sulfate (DSS) to induce colitis between day 14 and day 21. Animals were monitored regularly for arthritis and colitis severity (clinical score, hindpaw edema). Fecal microbiota was studied by 16S rRNA deep sequencing at critical time points (D14, D14, D21 & D41). At day 41, histological scoring of the intestines and ankles were performed at the end of experiment. Induction of colitis slightly delayed arthritis onset (2 ± 1 days of delay) and reduced its severity (5.75 ± 1.62 in arthritis only group vs 4.00 ± 1.48 in arthritis + colitis group (p = 0.02 at day 28) macroscopically and histologically. In contrast, colitis severity was not influenced by arthritis development. Induction of colitis promoted a modification of microbiota composition and a decrease of α-diversity. Fecal microbiota composition was different between "colitis" and "arthritis+colitis" groups during colitis development. Interestingly a milder decrease of bacterial diversity in the "arthritis+colitis" group was observed. Concomitant experimental colitis protects mice against collagen-induced arthritis and this is associated with changes in gut microbiome composition.

  12. Monitoring of Chemically Induced Colitis.

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    Reißig, Sonja; Weigmann, Benno

    2017-01-01

    Inflammation is a common symptom of inflammatory bowel disease (IBD). Actually, many experimental models of colitis exist and try to mimic the human situation in order to understand the pathogenesis of Crohn's disease and ulcerative colitis. These experimental models of inflammation can be characterized by specific parameters, which illustrate the proceeding inflammatory process. By use of these models potentially new reagents for improved therapeutic approaches can be analyzed. Here, we describe the TNBS-mediated colitis model and specify different parameters for the detailed characterization of the inflammatory process in experimental colitis models.

  13. Ghrelin ameliorates intestinal barrier dysfunction in experimental colitis by inhibiting the activation of nuclear factor-kappa B.

    Science.gov (United States)

    Cheng, Jian; Zhang, Lin; Dai, Weiqi; Mao, Yuqing; Li, Sainan; Wang, Jingjie; Li, Huanqing; Guo, Chuanyong; Fan, Xiaoming

    2015-02-27

    This study aimed to investigate the effect and underlying mechanism of ghrelin on intestinal barrier dysfunction in dextran sulfate sodium (DSS)-induced colitis. Acute colitis was induced in C57BL/6J mice by administering 2.5% DSS. Saline or 25, 125, 250 μg/kg ghrelin was administrated intraperitoneally (IP) to mice 1 day before colitis induction and on days 4, 5, and 6 after DSS administration. IP injection of a ghrelin receptor antagonist, [D-lys(3)]-GHRP-6, was performed immediately prior to ghrelin injection. Ghrelin (125 or 250 μg/kg) could reduce the disease activity index, histological score, and myeloperoxidase activities in experimental colitis, and also prevented shortening of the colon. Ghrelin could prevent the reduction of transepithelial electrical resistance and tight junction expression, and bolstered tight junction structural integrity and regulated cytokine secretion. Ultimately, ghrelin inhibited nuclear factor kappa B (NF-κB), inhibitory κB-α, myosin light chain kinase, and phosphorylated myosin light chain 2 activation. Ghrelin prevented the breakdown of intestinal barrier function in DSS-induced colitis. The protective effects of ghrelin on intestinal barrier function were mediated by its receptor GHSR-1a. The inhibition of NF-κB activation might be part of the mechanism underlying the effects of ghrelin that protect against barrier dysfunction. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Pharmaceutical Activation or Genetic Absence of ClC-2 Alters Tight Junctions During Experimental Colitis.

    Science.gov (United States)

    Jin, Younggeon; Pridgen, Tiffany A; Blikslager, Anthony T

    2015-12-01

    We have previously reported that the ClC-2 chloride channel has an important role in regulation of tight junction barrier function during experimental colitis, and the pharmaceutical ClC-2 activator lubiprostone initiates intestinal barrier repair in ischemic-injured intestine. Thus, we hypothesized that pharmaceutical ClC-2 activation would have a protective and therapeutic effect in murine models of colitis, which would be absent in ClC-2 mice. We administered lubiprostone to wild-type or ClC-2 mice with dextran sulfate sodium (DSS) or 2, 4, 5-trinitrobenzene sulfonic acid-induced colitis. We determined the severity of colitis and assessed intestinal permeability. Selected tight junction proteins were analyzed by Western blotting and immunofluorescence/confocal microscopy, whereas proliferative and differentiated cells were examined with special staining and immunohistochemistry. Oral preventive or therapeutic administration of lubiprostone significantly reduced the severity of colitis and reduced intestinal permeability in both DSS and trinitrobenzene sulfonic acid-induced colitis. Preventive treatment with lubiprostone induced significant recovery of the expression and distribution of selected sealing tight junction proteins in mice with DSS-induced colitis. In addition, lubiprostone reduced crypt proliferation and increased the number of differentiated epithelial cells. Alternatively, when lubiprostone was administered to ClC-2 mice, the protective effect against DSS colitis was limited. This study suggests a central role for ClC-2 in restoration of barrier function and tight junction architecture in experimental murine colitis, which can be therapeutically targeted with lubiprostone.

  15. Lycopene Ameliorates Experimental Colitis in Rats via Reducing Apoptosis and Oxidative Stress.

    Science.gov (United States)

    Gul Baykalir, Burcu; Aksit, Dilek; Dogru, Mustafa Selim; Hanım Yay, Arzu; Aksit, Hasan; Seyrek, Kamil; Attesahin, Ahmet

    2017-07-19

    Inflammatory bowel disease (IBD) is an inflammatory disorder involving colitis. Lycopene is a naturally occurring carotenoid that has attracted considerable attention as a potential chemopreventive agent. The impact of lycopene on colitis is currently unknown. The aim of this study was to investigate the protective effects of lycopene in a rat model of colitis induced by acetic acid. The animals were randomly divided into the following five groups: the control group, colitis group, colitis + sulfasalazine group as a positive control group, colitis + lycopene and lycopene groups. Colonic mucosal injury was assessed by biochemical and histopathological examinations. Malondialdehyde (MDA), superoxide dismutase (SOD) activity, total antioxidant status (TAS), ceruloplasmin (CPN), total sialic acid and iron (Fe) levels were evaluated in blood samples. MDA, SOD, TAS and DNA fragmentation levels were also measured in colon tissues. MDA (p lycopene in the colitis decreased MDA, total sialic acid and DNA fragmentation levels, while SOD activity (p lycopene ameliorated the biochemical and pathological alterations caused by colitis. The results obtained in this study indicate that lycopene may exert protective effects in experimental colitis and might, therefore, be useful for treatment of IBD.

  16. Central cholinergic activation of a vagus nerve - to spleen circuit alleviates experimental colitis

    Science.gov (United States)

    Ji, Hong; Rabbi, Mohammad F; Labis, Benoit; Pavlov, Valentin A; Tracey, Kevin J; Ghia, Jean-Eric

    2013-01-01

    The cholinergic anti-inflammatory pathway is an efferent vagus nerve-based mechanism that regulates immune responses and cytokine production through α7nicotinic-acetylcholinereceptor (α7nAChR) signaling. Decreased efferent vagus nerve activity is observed in inflammatory bowel disease (IBD). We determined whether central activation of this pathway alters inflammation in mice with colitis and the mediating role of a vagus nerve-to spleen circuit and α7nAChR signaling. Two experimental models of colitis were used in C57BL/6 mice. Central cholinergic activation induced by the acetylcholinesterase inhibitor galantamine or a muscarinic acetylcholine receptor agonist treatments resulted in reduced mucosal inflammation associated with decreased MHC II level and pro-inflammatory cytokine secretion by splenic CD11c+ cells mediated by α7nAChR signaling. The cholinergic anti-inflammatory efficacy was abolished in mice with vagotomy, splenic neurectomy or splenectomy. In conclusion, central cholinergic activation of a vagus nerve–to spleen circuit controls intestinal inflammation and this regulation can be explored to develop novel therapeutic strategies. PMID:23881354

  17. Central cholinergic activation of a vagus nerve-to-spleen circuit alleviates experimental colitis.

    Science.gov (United States)

    Ji, H; Rabbi, M F; Labis, B; Pavlov, V A; Tracey, K J; Ghia, J E

    2014-03-01

    The cholinergic anti-inflammatory pathway is an efferent vagus nerve-based mechanism that regulates immune responses and cytokine production through α7 nicotinic acetylcholine receptor (α7nAChR) signaling. Decreased efferent vagus nerve activity is observed in inflammatory bowel disease. We determined whether central activation of this pathway alters inflammation in mice with colitis and the mediating role of a vagus nerve-to-spleen circuit and α7nAChR signaling. Two experimental models of colitis were used in C57BL/6 mice. Central cholinergic activation induced by the acetylcholinesterase inhibitor galantamine or a muscarinic acetylcholine receptor agonist treatments resulted in reduced mucosal inflammation associated with decreased major histocompatibility complex II level and pro-inflammatory cytokine secretion by splenic CD11c⁺ cells mediated by α7nAChR signaling. The cholinergic anti-inflammatory efficacy was abolished in mice with vagotomy, splenic neurectomy, or splenectomy. In conclusion, central cholinergic activation of a vagus nerve-to-spleen circuit controls intestinal inflammation and this regulation can be explored to develop novel therapeutic strategies.

  18. Nitric oxide-releasing aspirin but not conventional aspirin improves healing of experimental colitis

    Science.gov (United States)

    Zwolinska-Wcislo, Malgorzata; Brzozowski, Tomasz; Ptak-Belowska, Agata; Targosz, Aneta; Urbanczyk, Katarzyna; Kwiecien, Slawomir; Sliwowski, Zbigniew

    2011-01-01

    AIM: To determine the effect of non-selective cyclooxygenase (COX) inhibitors, selective COX-2 inhibitors and nitric oxide (NO)-releasing aspirin in the healing of ulcerative colitis. METHODS: Rats with 2,4,6 trinitrobenzenesulfon-ic acid (TNBS)-induced colitis received intragastric (ig) treatment with vehicle, aspirin (ASA) (a non-selective COX inhibitor), celecoxib (a selective COX-2 inhibitor) or NO-releasing ASA for a period of ten days. The area of colonic lesions, colonic blood flow (CBF), myeloperoxidase (MPO) activity and expression of proinflammatory markers COX-2, inducible form of nitric oxide synthase (iNOS), IL-1β and tumor necrosis factor (TNF)-α were assessed. The effects of glyceryl trinitrate (GTN), a NO donor, and 2-(4-carboxyphenyl)-4,5-dihydro-4,4,5,5-​tetramethyl-1H-imidazolyl-1-oxy-3-oxide, onopotassium salt (carboxy-PTIO), a NO scavenger, administered without and with ASA or NO-ASA, and the involvement of capsaicin-sensitive afferent nerves in the mechanism of healing the experimental colitis was also determined. RESULTS: Rats with colitis developed macroscopic and microscopic colonic lesions accompanied by a significant decrease in the CBF, a significant rise in colonic weight, MPO activity and plasma IL-1β and TNF-α levels. These effects were aggravated by ASA and 5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole (SC-560), but not celecoxib and counteracted by concurrent treatment with a synthetic prostaglandin E2 (PGE2) analog. Treatment with NO-ASA dose-dependently accelerated colonic healing followed by a rise in plasma NOx content and CBF, suppression of MPO and downregulation of COX-2, iNOS, IL-1β and TNF-α mRNAs. Treatment with GTN, the NO donor, significantly inhibited the ASA-induced colonic lesions and increased CBF, while carboxy-PTIO or capsaicin-denervation counteracted the NO-ASA-induced improvement of colonic healing and the accompanying increase in the CBF. These effects were restored by co

  19. Cutting edge: IL-23 cross-regulates IL-12 production in T cell-dependent experimental colitis.

    Science.gov (United States)

    Becker, Christoph; Dornhoff, Heike; Neufert, Clemens; Fantini, Massimo C; Wirtz, Stefan; Huebner, Sabine; Nikolaev, Alexei; Lehr, Hans-Anton; Murphy, Andrew J; Valenzuela, David M; Yancopoulos, George D; Galle, Peter R; Karow, Margaret; Neurath, Markus F

    2006-09-01

    Although IL-12 and IL-23 share the common p40 subunit, IL-23, rather than IL-12, seems to drive the pathogenesis of experimental autoimmune encephalomyelitis and arthritis, because IL-23/p19 knockout mice are protected from disease. In contrast, we describe in this study that newly created LacZ knockin mice deficient for IL-23 p19 were highly susceptible for the development of experimental T cell-mediated TNBS colitis and showed even more severe colitis than wild-type mice by endoscopic and histologic criteria. Subsequent studies revealed that dendritic cells from p19-deficient mice produce elevated levels of IL-12, and that IL-23 down-regulates IL-12 expression upon TLR ligation. Finally, in vivo blockade of IL-12 p40 in IL-23-deficient mice rescued mice from lethal colitis. Taken together, our data identify cross-regulation of IL-12 expression by IL-23 as novel key regulatory pathway during initiation of T cell dependent colitis.

  20. Aberrant function of myeloid-derived suppressor cells (MDSCs) in experimental colitis and in inflammatory bowel disease (IBD) immune responses.

    Science.gov (United States)

    Kontaki, Eleni; Boumpas, Dimitrios T; Tzardi, Maria; Mouzas, Ioannis A; Papadakis, Konstantinos A; Verginis, Panayotis

    2017-05-01

    Myeloid-derived suppressor cells (MDSCs) encompass a novel population of suppressor cells and a potential candidate for cell-based therapies in inflammatory diseases. Herein, we investigated their immunomodulatory properties in experimental inflammatory colitis and T cell-mediated immune responses in inflammatory bowel disease (IBD) patients. MDSCs (defined as CD14 - HLA - DR -/low CD33 + CD15 + ) numbers were determined in peripheral blood (PB) from IBD patients. PB MDSC function was assessed in vitro. Experimental colitis was induced upon 2,4,6-trinitrobenzene sulfonic acid (TNBS) treatment and MDSCs were characterized by flow cytometry. The in vivo suppressive potential of bone marrow (BM)-derived MDSCs (BM-MDSCs) was tested by using both depleting and adoptive transfer strategies. MDSCs were enriched in the periphery of IBD patients during active disease. TNBS colitis induced amplification of MDSCs, particularly of the granulocytic (Ly6G + ) subset during the effector phase of disease. Of interest, BM-MDSCs potently suppressed CD4 +  T cell responses under steady state but failed to control colitis-associated immune responses in vivo. Mechanistically, under the colonic inflammatory milieu MDSCs switched phenotype (decreased proportion of Gr1 high and increased numbers of Gr1 low ) and downregulated CCAAT/enhancer-binding protein beta (CEBPβ) expression, a critical transcription factor for the suppressive function of MDSCs. In accordance with the murine data, human CD33  +  CD15 +  MDSCs from peripheral blood of IBD patients not only failed to suppress autologous T cell responses but instead enhanced T cell proliferation in vitro. Our findings demonstrate an aberrant function of MDSCs in experimental inflammatory colitis and in IBD-associated immune responses in vitro. Delineation of the mechanisms that underlie the loss of MDSCs function in IBD may provide novel therapeutic targets.

  1. Dipeptidyl peptidase expression during experimental colitis in mice

    DEFF Research Database (Denmark)

    Yazbeck, Roger; Sulda, Melanie L; Howarth, Gordon S

    2010-01-01

    We have previously demonstrated that inhibition of dipeptidyl peptidase (DP) activity partially attenuates dextran sulfate sodium (DSS) colitis in mice. The aim of this study was to further investigate the mechanisms of this protection....

  2. Effects of dextran sulfate sodium induced experimental colitis on cytochrome P450 activities in rat liver, kidney and intestine.

    Science.gov (United States)

    Hu, Nan; Huang, Yanjuan; Gao, Xuejiao; Li, Sai; Yan, Zhixiang; Wei, Bin; Yan, Ru

    2017-06-01

    Dextran sulfate sodium (DSS) induced experimental colitis presents a histologic resemblance to human ulcerative colitis (UC). Altered cytochrome P450s (CYPs) have been reported in this model and patients with UC. In this study, six CYPs activities were quantitatively determined in microsomes of liver (RLMs), kidney (RRMs) and intestine (RIMs) from rats with colitis at acute (5% DSS for 7 days, UCA) and remission (7-day DSS treatment followed by 7-day cessation, UCR) phases and compared with normal rats. Generally, CYPs activities varied with isoform, organ, and disease status. Hepatic CYP1A2, 2B1, 2C6/11, 2E1 and 3A1/2 activities were reduced by acute colitis and completely or partially restored after DSS was halted. Although DSS treatment decreased the Vmax of renal CYP2C6/11 and increased that of CYP2D2, their CLint, in vitro were comparable among normal, acute and remission stages. DSS treatment changed the kinetics of CYP3A1/2-mediated nifedipine metabolism in RRMs from biphasic to classical kinetics. Notably, CYP2D2 activity was elevated in liver and kidney in acute UC, while enhanced in liver and decreased in kidney in remission. In intestine, CYP3A1/2 activity was increased in UCA and further enhanced after DSS withdrawal. These findings highlight the necessity of quantifying enzyme activity for precision drug therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Experimental colitis delays and reduces the severity of collagen-induced arthritis in mice

    Science.gov (United States)

    Hablot, Julie; Peyrin-Biroulet, Laurent; Kokten, Tunay; El Omar, Reine; Netter, Patrick; Bastien, Claire; Jouzeau, Jean-Yves; Sokol, Harry

    2017-01-01

    Amongst extraintestinal manifestations (EIM) occurring in IBD patients, rheumatologic manifestations are the most frequent. Understanding the relationships between arthritis and colitis is a prerequisite to improving the management of these patients. Microbiota of patients with IBD or rheumatologic diseases, like spondyloarthritis (SpA) is modified compared to healthy individual. Thus, we have evaluated the impact of colitis in the development of arthritis in mice and we have analyzed microbiota changes. Collagen-induced arthritis (CIA) was induced at day 0 in DBA1 mice exposed or not to Dextran Sodium Sulfate (DSS) to induce colitis between day 14 and day 21. Animals were monitored regularly for arthritis and colitis severity (clinical score, hindpaw edema). Fecal microbiota was studied by 16S rRNA deep sequencing at critical time points (D14, D14, D21 & D41). At day 41, histological scoring of the intestines and ankles were performed at the end of experiment. Induction of colitis slightly delayed arthritis onset (2 ± 1 days of delay) and reduced its severity (5.75 ± 1.62 in arthritis only group vs 4.00 ± 1.48 in arthritis + colitis group (p = 0.02 at day 28) macroscopically and histologically. In contrast, colitis severity was not influenced by arthritis development. Induction of colitis promoted a modification of microbiota composition and a decrease of α-diversity. Fecal microbiota composition was different between “colitis” and “arthritis+colitis” groups during colitis development. Interestingly a milder decrease of bacterial diversity in the “arthritis+colitis” group was observed. Concomitant experimental colitis protects mice against collagen-induced arthritis and this is associated with changes in gut microbiome composition. PMID:28926599

  4. Colitis susceptibility in p47(phox-/-) mice is mediated by the microbiome.

    Science.gov (United States)

    Falcone, E Liana; Abusleme, Loreto; Swamydas, Muthulekha; Lionakis, Michail S; Ding, Li; Hsu, Amy P; Zelazny, Adrian M; Moutsopoulos, Niki M; Kuhns, Douglas B; Deming, Clay; Quiñones, Mariam; Segre, Julia A; Bryant, Clare E; Holland, Steven M

    2016-04-05

    Chronic granulomatous disease (CGD) is caused by defects in nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) complex subunits (gp91(phox) (a.k.a. Nox2), p47(phox), p67(phox), p22(phox), p40(phox)) leading to reduced phagocyte-derived reactive oxygen species production. Almost half of patients with CGD develop inflammatory bowel disease, and the involvement of the intestinal microbiome in relation to this predisposing immunodeficiency has not been explored. Although CGD mice do not spontaneously develop colitis, we demonstrate that p47(phox-/-) mice have increased susceptibility to dextran sodium sulfate colitis in association with a distinct colonic transcript and microbiome signature. Neither restoring NOX2 reactive oxygen species production nor normalizing the microbiome using cohoused adult p47(phox-/-) with B6Tac (wild type) mice reversed this phenotype. However, breeding p47(phox+/-) mice and standardizing the microflora between littermate p47(phox-/-) and B6Tac mice from birth significantly reduced dextran sodium sulfate colitis susceptibility in p47(phox-/-) mice. We found similarly decreased colitis susceptibility in littermate p47(phox-/-) and B6Tac mice treated with Citrobacter rodentium. Our findings suggest that the microbiome signature established at birth may play a bigger role than phagocyte-derived reactive oxygen species in mediating colitis susceptibility in CGD mice. These data further support bacteria-related disease in CGD colitis.

  5. Impact on Experimental Colitis of Vitamin D Receptor Deletion in Intestinal Epithelial or Myeloid Cells.

    Science.gov (United States)

    Leyssens, Carlien; Verlinden, Lieve; De Hertogh, Gert; Kato, Shigeaki; Gysemans, Conny; Mathieu, Chantal; Carmeliet, Geert; Verstuyf, Annemieke

    2017-07-01

    Inflammatory bowel diseases are gastrointestinal diseases that include Crohn disease and ulcerative colitis. The chronic inflammation is thought to result from an excessive inflammatory response to environmental factors such as luminal bacteria in genetically predisposed individuals. Studies have revealed that mice with impaired vitamin D signaling are more susceptible to experimental colitis. To better understand the contribution of vitamin D signaling in different cells of the gut to this disease, we investigated the effects of intestinal-specific or myeloid vitamin D receptor deletion. Our study addressed the importance of vitamin D receptor expression in intestinal epithelial cells using intestine-specific vitamin D receptor null mice and the contribution of vitamin D receptor expression in macrophages and granulocytes using myeloid-specific vitamin D receptor null mice in a dextran sodium sulfate model for experimental colitis. Loss of intestinal vitamin D receptor expression had no substantial effect on the clinical parameters of colitis and did not manifestly change mucosal cytokine expression. Inactivation of the vitamin D receptor in macrophages and granulocytes marginally affected colitis-associated symptoms but resulted in increased proinflammatory cytokine and increased β-defensin-1 expression in the colon descendens of mice with colitis. Intestinal deletion of the vitamin D receptor did not aggravate symptoms of chemically induced colitis. Loss of the vitamin D receptor in macrophages and granulocytes mildly affected colitis-associated symptoms but greatly increased proinflammatory cytokine expression in the inflamed colon, suggesting a prominent role for innate immune cell vitamin D signaling in controlling gut inflammation. Copyright © 2017 Endocrine Society.

  6. The effect of menthol on acute experimental colitis in rats.

    Science.gov (United States)

    Ghasemi-Pirbaluti, Masoumeh; Motaghi, Ehsan; Bozorgi, Homan

    2017-06-15

    Menthol is an aromatic compound with high antiinflammatory activity. The purpose of the current research is to investigate the effectiveness of menthol on acetic acid induced acute colitis in rats. Animals were injected with menthol (20 and 50 and 80mg/kg, i.p.) 24h prior to induction of colitis for 3 consecutive days. Menthol at medium and higher doses similar to dexamethasone as a reference drug significantly reduced body weight loss, macroscopic damage score, ulcer area, colon weight, colon length and improved hematocrit in rats with colitis. The histopathological examination also confirmed anti-colitic effects of menthol. Menthol also reduced significantly the colonic levels of tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β), interleukin 6 (IL-6) and myeloperoxidase (MPO) activity in inflamed colons. Thus, the findings of the current study provide evidence that menthol may be beneficial in patients suffering from acute ulcerative colitis. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Characterization of Growth Hormone Resistance in Experimental and Ulcerative Colitis

    DEFF Research Database (Denmark)

    Soendergaard, Christoffer; Kvist, Peter Helding; Thygesen, Peter

    2017-01-01

    Growth hormone (GH) resistance may develop as a consequence of inflammation during conditions such as inflammatory bowel disease, encompassing ulcerative colitis (UC). However, the specific role of the GH-insulin growth factor (IGF)-1-axis and/or the functional consequences of GH resistance in th...

  8. Neuronal control of experimental colitis occurs via sympathetic intestinal innervation

    NARCIS (Netherlands)

    Willemze, R. A.; Welting, O.; van Hamersveld, H. P.; Meijer, S. L.; Folgering, J. H. A.; Darwinkel, H.; Witherington, J.; Sridhar, A.; Vervoordeldonk, M. J.; Seppen, J.; de Jonge, W. J.

    2017-01-01

    Vagus nerve stimulation is currently clinically evaluated as a treatment for inflammatory bowel disease. However, the mechanism by which this therapeutic intervention can have an immune-regulatory effect in colitis remains unclear. We determined the effect of intestine-specific vagotomy or

  9. HVEM signalling promotes colitis.

    Directory of Open Access Journals (Sweden)

    Corinne Schaer

    Full Text Available BACKGROUND: Tumor necrosis factor super family (TNFSF members regulate important processes involved in cell proliferation, survival and differentiation and are therefore crucial for the balance between homeostasis and inflammatory responses. Several members of the TNFSF are closely associated with inflammatory bowel disease (IBD. Thus, they represent interesting new targets for therapeutic treatment of IBD. METHODOLOGY/PRINCIPAL FINDINGS: We have used mice deficient in TNFSF member HVEM in experimental models of IBD to investigate its role in the disease process. Two models of IBD were employed: i chemical-induced colitis primarily mediated by innate immune cells; and ii colitis initiated by CD4(+CD45RB(high T cells following their transfer into immuno-deficient RAG1(-/- hosts. In both models of disease the absence of HVEM resulted in a significant reduction in colitis and inflammatory cytokine production. CONCLUSIONS: These data show that HVEM stimulatory signals promote experimental colitis driven by innate or adaptive immune cells.

  10. Design approaches to experimental mediation.

    Science.gov (United States)

    Pirlott, Angela G; MacKinnon, David P

    2016-09-01

    Identifying causal mechanisms has become a cornerstone of experimental social psychology, and editors in top social psychology journals champion the use of mediation methods, particularly innovative ones when possible (e.g. Halberstadt, 2010, Smith, 2012). Commonly, studies in experimental social psychology randomly assign participants to levels of the independent variable and measure the mediating and dependent variables, and the mediator is assumed to causally affect the dependent variable. However, participants are not randomly assigned to levels of the mediating variable(s), i.e., the relationship between the mediating and dependent variables is correlational. Although researchers likely know that correlational studies pose a risk of confounding, this problem seems forgotten when thinking about experimental designs randomly assigning participants to levels of the independent variable and measuring the mediator (i.e., "measurement-of-mediation" designs). Experimentally manipulating the mediator provides an approach to solving these problems, yet these methods contain their own set of challenges (e.g., Bullock, Green, & Ha, 2010). We describe types of experimental manipulations targeting the mediator (manipulations demonstrating a causal effect of the mediator on the dependent variable and manipulations targeting the strength of the causal effect of the mediator) and types of experimental designs (double randomization, concurrent double randomization, and parallel), provide published examples of the designs, and discuss the strengths and challenges of each design. Therefore, the goals of this paper include providing a practical guide to manipulation-of-mediator designs in light of their challenges and encouraging researchers to use more rigorous approaches to mediation because manipulation-of-mediator designs strengthen the ability to infer causality of the mediating variable on the dependent variable.

  11. Tetraspanin CD9 Limits Mucosal Healing in Experimental Colitis

    Directory of Open Access Journals (Sweden)

    María Laura Saiz

    2017-12-01

    Full Text Available Tetraspanins are a family of proteins with four transmembrane domains that associate between themselves and cluster with other partner proteins, conforming a distinct class of membrane domains, the tetraspanin-enriched microdomains (TEMs. These TEMs constitute macromolecular signaling platforms that regulate key processes in several cellular settings controlling signaling thresholds and avidity of receptors. In this study, we investigated the role of CD9, a tetraspanin that regulates major biological processes such as cell migration and immunological responses, in two mouse models of colitis that have been used to study the pathogenesis of inflammatory bowel disease (IBD. Previous in vitro studies revealed an important role in the interaction of leukocytes with inflamed endothelium, but in vivo evidence of the involvement of CD9 in inflammatory diseases is scarce. Here, we studied the role of CD9 in the pathogenesis of colitis in vivo. Colitis was induced by administration of dextran sodium sulfate (DSS, a chemical colitogen that causes epithelial disruption and intestinal inflammation. CD9−/− mice showed less severe colitis than wild-type counterparts upon exposure to DSS (2% solution and enhanced survival in response to a lethal DSS dose (4%. Decreased neutrophil and macrophage cell infiltration was observed in colonic tissue from CD9−/− animals, in accordance with their lower serum levels of TNF-α, IL-6, and other proinflammatory cytokines in the colon. The specific role of CD9 in IBD was further dissected by transfer of CD4+ CD45RBhi naive T cells into the Rag1−/− mouse colitis model. However, no significant differences were observed in these settings between both groups, ruling out a role for CD9 in IBD in the lymphoid compartment. Experiments with bone marrow chimeras revealed that CD9 in the non-hematopoietic compartment is involved in colon injury and limits the proliferation of epithelial cells. Our data indicate that CD9

  12. Sulfate-reducing bacteria stimulate gut immune responses and contribute to inflammation in experimental colitis.

    Science.gov (United States)

    Figliuolo, Vanessa Ribeiro; Dos Santos, Liliane Martins; Abalo, Alessandra; Nanini, Hayandra; Santos, Angela; Brittes, Nilda M; Bernardazzi, Claudio; de Souza, Heitor Siffert Pereira; Vieira, Leda Quercia; Coutinho-Silva, Robson; Coutinho, Claudia Mara Lara Melo

    2017-11-15

    The intestinal microbiota is critical for mammalian immune system development and homeostasis. Sulfate-reducing bacteria (SRB) are part of the normal gut microbiota, but their increased levels may contribute to colitis development, likely in association with hydrogen sulfide (H2S) production. Here, we investigated the effects of SRB in the gut immune response in germ-free mice, and in experimental colitis. After 7days of colonization with Desulfovibrio indonesiensis or with a human SRB consortium (from patients with colitis), germ-free mice exhibited alterations in the colonic architecture, with increased cell infiltration in the lamina propria. SRB colonization upregulated the Th17 and Treg profiles of cytokine production/cell activation, in T cells from mesenteric lymph nodes. These alterations were more pronounced in mice colonized with the human SRB consortium, although D. indonesiensis colonization produced higher levels of H2S. Importantly, the colon of C57BL/6 mice with colitis induced by TNBS or oxazolone had increased SRB colonization, and the administration of D. indonesiensis to mice with TNBS-induced colitis clearly exacerbated the alterations in colonic architecture observed in the established disease, and also increased mouse weight loss. We conclude that SRB contribute to immune response activation in the gut and play an important role in colitis development. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Growth hormone secretagogue receptor is important in the development of experimental colitis.

    Science.gov (United States)

    Liu, Zhen-Ze; Wang, Wei-Gang; Li, Qing; Tang, Miao; Li, Jun; Wu, Wen-Ting; Wan, Ying-Han; Wang, Zhu-Gang; Bao, Shi-San; Fei, Jian

    2015-01-01

    Growth hormone secretagogue receptor (GHSR) and its ligand, ghrelin, are important modulators in weight control and energy homeostasis. Recently, ghrelin is also involved in experimental colitis, but the role of GHSR in the development of colitis is unclear. The aim was to examine the underlying mechanism of GHSR in IBD development. The temporal expression of GHSR/ghrelin was determined in dextran sulphate sodium (DSS) induced colitis in Wt mice. The severity of DSS induced colitis from GHSR(-/-) and WT mice was compared at clinical/pathological levels. Furthermore, the function of macrophages was evaluated in vivo and in vitro. Lack of GHSR attenuated colitis significantly at the clinical and pathological levels with reduced colonic pro-inflammatory cytokines (P < 0.05). This is consistent with the observation of less colonic macrophage infiltration and TLRs expression from DSS-treated GHSR(-/-) mice compared to WT mice (P < 0.05). Furthermore, there was significantly reduced pro-inflammatory cytokines in LPS-stimulated macrophages in vitro from GHSR(-/-) mice than WT mice (P < 0.05). Moreover, D-lys(3)-GHRP6 (a GHSR antagonist) reduced LPS-induced macrophage pro-inflammatory cytokines from WT mice in vitro. GHSR contributes to development of acute DSS-induced colitis, likely via elevated pro-inflammatory cytokines and activation of macrophages. These data suggest GHSR as a potential therapeutic target for IBD.

  14. The effect of stinging nettle (Urtica dioica) seed oil on experimental colitis in rats.

    Science.gov (United States)

    Genc, Zeynep; Yarat, Aysen; Tunali-Akbay, Tugba; Sener, Goksel; Cetinel, Sule; Pisiriciler, Rabia; Caliskan-Ak, Esin; Altıntas, Ayhan; Demirci, Betul

    2011-12-01

    This study investigated the effect of Urtica dioica, known as stinging nettle, seed oil (UDO) treatment on colonic tissue and blood parameters of trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats. Experimental colitis was induced with 1 mL of TNBS in 40% ethanol by intracolonic administration with a 8-cm-long cannula with rats under ether anesthesia, assigned to a colitis group and a colitis+UDO group. Rats in the control group were given saline at the same volume by intracolonic administration. UDO (2.5 mL/kg) was given to the colitis+UDO group by oral administration throughout a 3-day interval, 5 minutes later than colitis induction. Saline (2.5 mL/kg) was given to the control and colitis groups at the same volume by oral administration. At the end of the experiment macroscopic lesions were scored, and the degree of oxidant damage was evaluated by colonic total protein, sialic acid, malondialdehyde (MDA), and glutathione levels, collagen content, tissue factor activity, and superoxide dismutase and myeloperoxidase activities. Colonic tissues were also examined by histological and cytological analysis. Pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-1β, and interleukin-6), lactate dehydrogenase activity, and triglyceride and cholesterol levels were analyzed in blood samples. We found that UDO decreased levels of pro-inflammatory cytokines, lactate dehydrogenase, triglyceride, and cholesterol, which were increased in colitis. UDO administration ameliorated the TNBS-induced disturbances in colonic tissue except for MDA. In conclusion, UDO, through its anti-inflammatory and antioxidant actions, merits consideration as a potential agent in ameliorating colonic inflammation.

  15. 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

  16. Sodium chloride-enriched Diet Enhanced Inflammatory Cytokine Production and Exacerbated Experimental Colitis in Mice.

    Science.gov (United States)

    Monteleone, Ivan; Marafini, Irene; Dinallo, Vincenzo; Di Fusco, Davide; Troncone, Edoardo; Zorzi, Francesca; Laudisi, Federica; Monteleone, Giovanni

    2017-02-01

    Environmental factors are supposed to play a decisive role in the pathogenesis of inflammatory bowel diseases [IBDs]. Increased dietary salt intake has been linked with the development of autoimmune diseases, but the impact of a salt-enriched diet on the course of IBD remains unknown. In this study, we examined whether high salt intake alters mucosal cytokine production and exacerbates colitis. Normal intestinal lamina propria mononuclear cells [LPMCs] were activated with anti-CD3/CD28 in the presence or absence of increasing concentrations of sodium chloride [NaCl] and/or SB202190, a specific inhibitor of p38/MAP Kinase. For in vivo experiments, a high dose of NaCl was administered to mice 15 days before induction of trinitrobenzene-sulfonic acid [TNBS]-colitis or dextran sulfate sodium [DSS]-colitis. In parallel, mice were given SB202190 before induction of TNBS-colitis. Transcription factors and effector cytokines were evaluated by flow-cytometry and real-time PCR. IL-17A, IL-23R, TNF-α, and Ror-γT were significantly increased in human LPMCs following NaCl exposure, while there was no significant change in IFN-γ, T-bet or Foxp3. Pharmacologic inhibition of p38/MAPK abrogated the NaCl-inducing effect on LPMC-derived cytokines. Mice receiving the high-salt diet developed a more severe colitis than control mice, and this effect was preventable by SB202190. Our data indicated that exposure of intestinal mononuclear cells to a high-NaCl diet enhanced effector cytokine production and contributed to the exacerbation of experimental colitis in mice. Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  17. 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.

  18. Preventive therapy of experimental colitis with selected iron chelators and anti-oxidants

    Directory of Open Access Journals (Sweden)

    Mohsen Minaiyan

    2012-01-01

    Conclusions: Maltol with the highest test dose was capable to protect against experimentally induced colitis. Kojic acid and vitamin E were not effective in this animal model of colon inflammation. More detailed studies are warranted to explore the mechanisms involved in anti-colitic property of maltol and to explain ineffectiveness of kojic acid and vitamin E.

  19. Effect of secondary lymphoid tissue chemokine suppression on experimental ulcerative colitis in mice.

    Science.gov (United States)

    Zhang, H; Zhang, X; Ding, X; Cao, W; Qu, L; Zhou, G

    2014-04-29

    The secondary lymphoid tissue chemokine (CCL21) is closely associated with lymphoid homing and anti-tumor immune responses. CCL21 also has a chemotactic effect on intestinal lymphocytes. This study mainly focused on CCL21 expression in experimental ulcerative colitis and on the effects of CCL21 suppression on this disease in mice. The mouse colitis model was induced by dextran sulfate sodium (DSS) in 40 female BALB/c mice that were equally distributed into five groups: control, DSS, propylene glycol, triptolide (TL), and dexamethasone treatment groups. The disease activity index, general morphology score of the colon, and histological pathology score of colon tissues were evaluated. CCL21 expression was examined in colons of mice by immunohistochemistry, reverse transcription-polymerase chain reaction, and Western blotting analysis. CCL21 was upregulated in the mouse model of ulcerative colitis (control group vs DSS group/propylene glycol group, Pdexamethasone treatments improved colitis symptoms and decreased CCL21 expression (TL group/dexamethasone group vs DSS group/propylene glycol group, PSuppression of CCL21 expression decreased damage induced from ulcerative colitis, indicating that CCL21 targeted therapy might be an effective treatment for this disease.

  20. Effect of ES products from Anisakis (Nematoda: Anisakidae) on experimentally induced colitis in adult zebrafish

    DEFF Research Database (Denmark)

    Haarder, Simon; Kania, Per Walter; Holm, Thomas

    2017-01-01

    with helminth-derived substances have supported this notion, but underlying mechanisms remain unclear. This study therefore dissects to what extent a series of immune-related genes are modulated in zebrafish with experimentally induced colitis following exposure to excretory-secretory (ES) products isolated...... from larval Anisakis, a widely distributed fish nematode. Adult zebrafish intrarectally exposed to the colitis-inducing agent TNBS developed severe colitis leading to 80% severe morbidity, but if co-injected (ip) with Anisakis ES products, the morbidity rate was 50% at the end of the experiment (48...... hours post-exposure). Gene expression studies of TNBS-treated zebrafish showed clear upregulation of a range of genes encoding inflammatory cytokines and effector molecules and some induction of genes related to the adaptive response. A distinct innate-driven immune response was seen in both TNBS...

  1. Digoxin Attenuates Murine Experimental Colitis by Downregulating Th17-related Cytokines.

    Science.gov (United States)

    Tani, Shinya; Takano, Ryosuke; Tamura, Satoshi; Oishi, Shinji; Iwaizumi, Moriya; Hamaya, Yasushi; Takagaki, Kosuke; Nagata, Toshi; Seto, Shintaro; Horii, Toshinobu; Kosugi, Isao; Iwashita, Toshihide; Osawa, Satoshi; Furuta, Takahisa; Miyajima, Hiroaki; Sugimoto, Ken

    2017-05-01

    Digoxin, a cardiac glycoside used for the treatment of heart failure, was reported to inhibit the retinoid-related orphan receptor gamma t (RORγt) and attenuate the severity of experimental autoimmune encephalomyelitis and arthritis in mice. However, the effects of digoxin in a mice model of inflammatory bowel disease have not been elucidated. Colitis was induced in severe combined immunodeficiency mice by adoptive transfer of CD45RB CD4 T cells. Digoxin or a vehicle was injected into mice with colitis intraperitoneally every other day and changes in body weight were evaluated. After 6 to 8 weeks, the treated mice were killed and evaluated for histological score, T-cell subset, and cytokine messenger RNA (mRNA) expression in the colonic tissue. Wasting disease and histological damage were significantly attenuated in digoxin-treated mice with colitis compared with those in the vehicle-treated mice. In addition, the mRNAs of Th17-related cytokines were downregulated, whereas those of interleukin-10 were upregulated in the colonic mucosa of digoxin-treated mice. However, unexpectedly, the mRNA expression level of tumor necrosis factor alpha did not decrease in the colonic mucosa of digoxin-treated mice with colitis. This observation suggests that digoxin may ameliorate colitis by a tumor necrosis factor alpha-independent pathway. This study has shown for the first time that treatment with digoxin can ameliorate murine experimental colitis. This finding suggests that the suppression of Th17 using reagents such as digoxin could be effective in treating Crohn's disease refractory to anti-tumor necrosis factor alpha therapy.

  2. 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. Copyright © 2015 Elsevier Ltd. All

  3. Therapeutic effects of four strains of probiotics on experimental colitis in mice.

    Science.gov (United States)

    Chen, Lin Lin; Wang, Xue Hong; Cui, Yi; Lian, Guang Hui; Zhang, Jie; Ouyang, Chun Hui; Lu, Fang Gen

    2009-01-21

    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. 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. 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 +/- 0.2 vs 8.6 +/- 0.4, P probiotics-treated mice was longer than that of mice in the control group (10.3 +/- 0.34 vs 8.65 +/- 0.77, P 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. 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.

  4. Effect of Mesalamine and Prednisolone on TNBS Experimental Colitis, following Various Doses of Orally Administered Iron

    Directory of Open Access Journals (Sweden)

    John K. Triantafillidis

    2014-01-01

    Full Text Available Background. Experimental data suggest that oral iron (I. supplementation can worsen colitis in animals. Aim. To investigate the influence of various concentrations of orally administered I. in normal gut mucosa and mucosa of animals with TNBS colitis, as well as the influence of Mesalamine (M. and Prednisolone (P. on the severity of TNBS colitis following orally administered I. Methods and Materials. 156 Wistar rats were allocated into 10 groups. Colitis was induced by TNBS. On the 8th day, all animals were euthanatized. Activity of colitis and extent of tissue damage were assessed histologically. The levels of tissue tumor necrosis factor-α (t-TNF-α and tissue malondialdehyde (t-MDA were estimated in all animal groups. Results. Moderate and high I. supplementation induced inflammation in the healthy colon and increased the activity of the experimentally induced TNBS colitis. Administration of M. on TNBS colitis following moderate iron supplementation (0.3 g/Kg diet resulted in a significant improvement in the overall histological score as well as in two individual histological parameters. M. administration, however, did not significantly reduce the t-TNF-α levels (17.67±4.92 versus 14.58±5.71, P=0.102, although it significantly reduced the t-MDA levels (5.79±1.55 versus 3.67±1.39, P=0.000. Administration of M. on TNBS colitis following high iron supplementation (3.0 g/Kg diet did not improve the overall histological score and the individual histological parameters, neither reduced the levels of t-TNF-α (16.57 ± 5.61 versus 14.65±3.88, P=0.296. However, M. significantly reduced the t-MDA levels (5.99±1.37 versus 4.04±1.41, P=0.000. Administration of P. on TNBS colitis after moderate iron supplementation resulted in a significant improvement in the overall histological score as well as in three individual histological parameters. P. also resulted in a significant reduction in the t-TNF-α levels (17.67±4.92 versus 12.64±3

  5. Alterations of testosterone metabolism in microsomes from rats with experimental colitis induced by dextran sulfate sodium.

    Science.gov (United States)

    Huang, Yanjuan; Hu, Nan; Gao, Xuejiao; Yan, Zhixiang; Li, Sai; Jing, Wanghui; Yan, Ru

    2015-05-05

    Down-regulation of some hepatic cytochrome P450s (CYP450s) was observed in patients and animals with ulcerative colitis (UC). This study examined changes of CYP450s activities in microsomes of liver (RLMs), intestine (RIMs) and kidney (RRMs) from rats with experimental acute colitis induced by 5% dextran sulfate sodium (DSS) for 7days and those receiving DSS treatment followed by 7-d cessation through measuring 6α-(CYP1A1), 7α-(CYP2A1), 16α-(CYP2C11) and 2β-/6β-(CYP3A2) hydroxytestosterone (OHT) formed from testosterone. Both pro-(IL-1β, IL-6, TNF-α) and anti-(IL-4, IL-10) inflammatory cytokines were elevated in acute colitis, while the production of the former was enhanced and that of the latter declined by DSS withdrawal. In RLMs, the CYP2A1 activity was significantly increased at DSS stimulation and partially returned to normal level when DSS treatment was terminated. Activity of other CYP450s were decreased by acute colitis and remained after DSS withdrawal. In RRMs, formations of 6α-, 16α- and 2β-OHT significantly declined in acute colitis and DSS termination further potentiated the down-regulation, while 7α-OHT formation was suppressed at DSS stimulation and remained after DSS withdrawal. The formation of 6β-OHT only showed significant decrease after DSS withdrawal. Two metabolites (6α- and 6β-OHT) formed in RIMs and 6β-OHT formation was significantly decreased by DSS stimulation and continued after DSS treatment halted. These findings indicate that the alterations of CYP450s activities vary with organ, CYP isoforms and colitis status, which arouse cautions on efficacy and toxicity of drug therapy during disease progression. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  6. Comparison of parenteral nutrition and enteral feeding with pectin in experimental colitis in the rat.

    Science.gov (United States)

    Rolandelli, R H; Saul, S H; Settle, R G; Jacobs, D O; Trerotola, S O; Rombeau, J L

    1988-04-01

    The effect of a pectin-supplemented enteral diet on experimental colitis was compared with parenteral nutrition and with a pectin-free enteral diet. Forty-five rats had feeding catheters placed into either the stomach (IG, n = 31) or the superior vena cava (IV, n = 14) and then received acetic acid (colitis) or saline (control) enemas. After the enema, all rats received the same diet, either IG or IV, for 6 d except for 15 rats (IGP, 9 colitis and 6 controls), which had 1% pectin added to the diet. At the end of the feeding period the IGP group had significantly less colonic inflammation and/or necrosis than either IV (p less than 0.03) or IG (p less than 0.04) groups. Nitrogen balance, serum albumin, total iron-binding capacity and body weight did not differ significantly among dietary regimens. Thus, the degree of bowel injury in experimental colitis was decreased when animals were fed a pectin-supplemented enteral diet and this effect was independent of nutritional status.

  7. Preventive and therapeutic effects of blueberry (Vaccinium corymbosum) extract against DSS-induced ulcerative colitis by regulation of antioxidant and inflammatory mediators.

    Science.gov (United States)

    Pervin, Mehnaz; Hasnat, Md Abul; Lim, Ji-Hong; Lee, Yoon-Mi; Kim, Eun Ok; Um, Byung-Hun; Lim, Beong Ou

    2016-02-01

    Inflammatory bowel disease (IBD) is an inflammatory disorder caused by hyperactivation of effector immune cells that produce high levels of proinflammatory cytokines. The aims of our study were to determine whether orally administered blueberry extract (BE) could attenuate or prevent the development of experimental colitis in mice and to elucidate the mechanism of action. Female Balb/C mice (n=7) were randomized into groups differing in treatment conditions (prevention and treatment) and dose of BE (50 mg/kg body weight). Acute ulcerative colitis was induced by oral administration of 3% dextran sodium sulfate for 7 days in drinking water. Colonic mucosal injury was assessed by clinical, macroscopic, biochemical and histopathological examinations. BE significantly decreased disease activity index and improved the macroscopic and histological score of colons when compared to the colitis group (P<.05). BE markedly attenuated myeloperoxidase accumulation (colitis group 54.97±2.78 nmol/mg, treatment group 30.78±1.33 nmol/mg) and malondialdehyde in colon and prostaglandin E2 level in serum while increasing the levels of superoxide dismutase and catalase (colitis group 11.94±1.16 U/ml, BE treatment group 16.49±0.39 U/ml) compared with the colitis group (P<.05). mRNA levels of the cyclooxygenase (COX)-2, interferon-γ, interleukin (IL)-1β and inducible nitric oxide synthase cytokines were determined by reverse transcriptase polymerase chain reaction. Immunohistochemical analysis showed that BE attenuates the expression of COX-2 and IL-1β in colonic tissue. Moreover, BE reduced the nuclear translocation of nuclear transcription factor kappa B (NF-κB) by immunofluorescence analysis. Thus, the anti-inflammatory effect of BE at colorectal sites is a result of a number of mechanisms: antioxidation, down-regulation of the expression of inflammatory mediators and inhibition of the nuclear translocation of NF-κB. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Beneficial effects of THSG on acetic acid-induced experimental colitis: involvement of upregulation of PPAR-γ and inhibition of the Nf-Κb inflammatory pathway.

    Science.gov (United States)

    Zeng, Cheng; Xiao, Jun-Hua; Chang, Mu-Jun; Wang, Jia-Ling

    2011-10-12

    The polyphenolic compound 2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucoside (THSG) has been shown to possess anti-inflammatory effects. Here, we examined the effects of THSG on experimental mice with colitis induced by acetic acid and whether the underlying mechanisms were associated with the PPAR-γ and NF-κB pathways. Mice were randomized into six equal groups: normal, colitis model, THSG (10, 30, 60 mg·kg(-1)) and mesalazine. The mice were administered 10, 30, 60 mg·kg(-1) THSG or 100 mg·kg-1 mesalazine or saline once daily by intragastric administration for 7 days after induction of colitis by acetic acid irrigation. THSG dramatically attenuated acetic acid-induced colon lesions, including reversing the body weight loss and improving histopathological changes. THSG apparently decreased the increase of malondialdehyde (MDA) which is a marker of lipid peroxidation. THSG appears to exert its beneficial effects on acetic acid-induced experimental colitis through upregulation of PPAR-γ mRNA and protein levels and inhibition of the NF-κB pathway, which in turn decreases the protein overexpression of the downstream inflammatory mediators TNF-α, IL-6 and COX-2. The effect of THSG 60 mg·kg(-1) on PPAR-γ mRNA expression was higher than that of mesalazine. THSG may thus be a promising new candidate or lead compound for the treatment of IBD.

  9. Beneficial Effects of THSG on Acetic Acid-Induced Experimental Colitis: Involvement of Upregulation of PPAR-γ and Inhibition of the Nf-Κb Inflammatory Pathway

    Directory of Open Access Journals (Sweden)

    Jia-Ling Wang

    2011-10-01

    Full Text Available The polyphenolic compound 2,3,5,4′-tetrahydroxystilbene-2-O-beta-D-glucoside (THSG has been shown to possess anti-inflammatory effects. Here, we examined the effects of THSG on experimental mice with colitis induced by acetic acid and whether the underlying mechanisms were associated with the PPAR-γ and NF-κB pathways. Mice were randomized into six equal groups: normal, colitis model, THSG (10, 30, 60 mg·kg−1 and mesalazine. The mice were administered 10, 30, 60 mg·kg−1 THSG or 100 mg·kg−1 mesalazine or saline once daily by intragastric administration for 7 days after induction of colitis by acetic acid irrigation. THSG dramatically attenuated acetic acid-induced colon lesions, including reversing the body weight loss and improving histopathological changes. THSG apparently decreased the increase of malondialdehyde (MDA which is a marker of lipid peroxidation. THSG appears to exert its beneficial effects on acetic acid-induced experimental colitis through upregulation of PPAR-γ mRNA and protein levels and inhibition of the NF-κB pathway, which in turn decreases the protein overexpression of the downstream inflammatory mediators TNF-α, IL-6 and COX-2. The effect of THSG 60 mg·kg−1 on PPAR-γ mRNA expression was higher than that of mesalazine. THSG may thus be a promising new candidate or lead compound for the treatment of IBD.

  10. Preventive and curative effect of Pistacia lentiscus oil in experimental colitis.

    Science.gov (United States)

    Naouar, Mustafa S; Mekki, Lilia Zouiten; Charfi, Lamia; Boubaker, Jalel; Filali, Azza

    2016-10-01

    to investigate the anti-inflammatory effect of the Pistacia lentiscus oil in experimental colitis model. Colitis was induced in male rats by instillation of 2,4,6-trinitrobenzenesulfonic acid (TNBS) in all groups. The experimental groups consisted of: 5 rats received Lentisc oil 2months before colitis induction (preventive group), 5 rats received the oil on the day of colitis induction (curative group) and 5 control rats. Lentisc oil was extracted from the ripe fruit of the plant by the cold press method and was analyzed by spectro-chromatography. Lentisc oil has been inserted with a standard diet at the dose of 30mg oil/100g of food/rat. The lentisc oil sample is composed mainly by Oleic acid (47.96%), Palmitic acid (27.94%) and Linoleic acid (20.22%).There was a significant difference between control rats and treated rats with lentisc oil concerned body mass (p=0.009), bleeding index (p=0.005 and p=0.018) and diarrhea (p=0.012). Histological examination revealed a clear difference between the control and preventive groups with disappearance of erosion, decreased of cryptitis, irregular crypts and crypt loss in the preventive group. Curative group showed a significant decrease of ulceration, hyperplasia, cryptitis, irregular crypts and crypt loss compared to the control group. There was an attenuation of inflammation in the preventive group compared to the curative group without statistically significant. Lentisc oil administration could provide a protective effect on intestinal inflammation in colitis rats induced by TNBS mainly when it is administered at a young age in preventive mode. This beneficial effect would involve a modification of arachidonic acid metabolism. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  11. Experimental Colitis Is Attenuated by Cardioprotective Diet Supplementation That Reduces Oxidative Stress, Inflammation, and Mucosal Damage

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    Hilda Vargas Robles

    2016-01-01

    Full Text Available Inflammatory bowel diseases (IBD such as ulcerative colitis (UC and Crohn’s disease (CD are multifactorial, relapsing disorders of the gastrointestinal tract. However, the etiology is still poorly understood but involves altered immune responses, epithelial dysfunction, environmental factors, and nutrition. Recently, we have shown that the diet supplement corabion has cardioprotective effects due to reduction of oxidative stress and inflammation. Since oxidative stress and inflammation are also prominent risk factors in IBD, we speculated that corabion also has beneficial effects on experimental colitis. Colitis was induced in male mice by administration of 3.5% (w/v dextran sulfate sodium (DSS in drinking water for a period of 3 or 7 days with or without daily gavage feeding of corabion consisting of vitamin C, vitamin E, L-arginine, and eicosapentaenoic and docosahexaenoic acid. We found that corabion administration attenuated DSS-induced colon shortening, tissue damage, and disease activity index during the onset of colitis. Mechanistically, these effects could be explained by reduced neutrophil recruitment, oxidative stress, production of proinflammatory cytokines, and internalization of the junctional proteins ZO-1 and E-cadherin leading to less edema formation. Thus, corabion may be a useful diet supplement for the management of chronic inflammatory intestinal disorders such as IBD.

  12. Experimental Colitis Is Attenuated by Cardioprotective Diet Supplementation That Reduces Oxidative Stress, Inflammation, and Mucosal Damage.

    Science.gov (United States)

    Vargas Robles, Hilda; Citalán Madrid, Alí Francisco; García Ponce, Alexander; Silva Olivares, Angelica; Shibayama, Mineko; Betanzos, Abigail; Del Valle Mondragón, Leonardo; Nava, Porfirio; Schnoor, Michael

    2016-01-01

    Inflammatory bowel diseases (IBD) such as ulcerative colitis (UC) and Crohn's disease (CD) are multifactorial, relapsing disorders of the gastrointestinal tract. However, the etiology is still poorly understood but involves altered immune responses, epithelial dysfunction, environmental factors, and nutrition. Recently, we have shown that the diet supplement corabion has cardioprotective effects due to reduction of oxidative stress and inflammation. Since oxidative stress and inflammation are also prominent risk factors in IBD, we speculated that corabion also has beneficial effects on experimental colitis. Colitis was induced in male mice by administration of 3.5% (w/v) dextran sulfate sodium (DSS) in drinking water for a period of 3 or 7 days with or without daily gavage feeding of corabion consisting of vitamin C, vitamin E, L-arginine, and eicosapentaenoic and docosahexaenoic acid. We found that corabion administration attenuated DSS-induced colon shortening, tissue damage, and disease activity index during the onset of colitis. Mechanistically, these effects could be explained by reduced neutrophil recruitment, oxidative stress, production of proinflammatory cytokines, and internalization of the junctional proteins ZO-1 and E-cadherin leading to less edema formation. Thus, corabion may be a useful diet supplement for the management of chronic inflammatory intestinal disorders such as IBD.

  13. 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......2 had positive effect only in DSS-induced colitis. The TFF3 monomer was without any effects in both models. Treatment effect was most pronounced in the middle part of the colon, closest to the tip of the catheter. Injected TFF peptides, especially the TFF3 monomer, aggravated the colitis score...... 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....

  14. 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

  15. 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

    2011-09-28

    To evaluate whether combination therapy with anti-tumour necrosis factor α (TNFα) antibody and Zn acetate is beneficial in dextran sodium sulphate (DSS) colitis. 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. 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). 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.

  16. Downregulation of FoxC2 Increased Susceptibility to Experimental Colitis: Influence of Lymphatic Drainage Function?

    Science.gov (United States)

    Becker, Felix; Potepalov, Sergey; Shehzahdi, Romana; Bernas, Michael; Witte, Marlys; Abreo, Fleurette; Traylor, James; Orr, Wayne A.; Tsunoda, Ikuo

    2015-01-01

    Background: Although inflammation-induced expansion of the intestinal lymphatic vasculature (lymphangiogenesis) is known to be a crucial event in limiting inflammatory processes, through clearance of interstitial fluid and immune cells, considerably less is known about the impact of an impaired lymphatic clearance function (as seen in inflammatory bowel diseases) on this cascade. We aimed to investigate whether the impaired intestinal lymphatic drainage function observed in FoxC2(+/−) mice would influence the course of disease in a model of experimental colitis. Methods: Acute dextran sodium sulfate colitis was induced in wild-type and haploinsufficient FoxC2(+/−) mice, and survival, disease activity, colonic histopathological injury, neutrophil, T-cell, and macrophage infiltration were evaluated. Functional and structural changes in the intestinal lymphatic vessel network were analyzed, including submucosal edema, vessel morphology, and lymphatic vessel density. Results: We found that FoxC2 downregulation in FoxC2(+/−) mice significantly increased the severity and susceptibility to experimental colitis, as displayed by lower survival rates, increased disease activity, greater histopathological injury, and elevated colonic neutrophil, T-cell, and macrophage infiltration. These findings were accompanied by structural (dilated torturous lymphatic vessels) and functional (greater submucosal edema, higher immune cell burden) changes in the intestinal lymphatic vasculature. Conclusions: These results indicate that sufficient lymphatic clearance plays a crucial role in limiting the initiation and perpetuation of experimental colitis and those disturbances in the integrity of the intestinal lymphatic vessel network could intensify intestinal inflammation. Future therapies might be able to exploit these processes to restore and maintain adequate lymphatic clearance function in inflammatory bowel disease. PMID:25822012

  17. Downregulation of FoxC2 Increased Susceptibility to Experimental Colitis: Influence of Lymphatic Drainage Function?

    Science.gov (United States)

    Becker, Felix; Potepalov, Sergey; Shehzahdi, Romana; Bernas, Michael; Witte, Marlys; Abreo, Fleurette; Traylor, James; Orr, Wayne A; Tsunoda, Ikuo; Alexander, Jonathan Steven

    2015-06-01

    Although inflammation-induced expansion of the intestinal lymphatic vasculature (lymphangiogenesis) is known to be a crucial event in limiting inflammatory processes, through clearance of interstitial fluid and immune cells, considerably less is known about the impact of an impaired lymphatic clearance function (as seen in inflammatory bowel diseases) on this cascade. We aimed to investigate whether the impaired intestinal lymphatic drainage function observed in FoxC2 mice would influence the course of disease in a model of experimental colitis. Acute dextran sodium sulfate colitis was induced in wild-type and haploinsufficient FoxC2 mice, and survival, disease activity, colonic histopathological injury, neutrophil, T-cell, and macrophage infiltration were evaluated. Functional and structural changes in the intestinal lymphatic vessel network were analyzed, including submucosal edema, vessel morphology, and lymphatic vessel density. We found that FoxC2 downregulation in FoxC2 mice significantly increased the severity and susceptibility to experimental colitis, as displayed by lower survival rates, increased disease activity, greater histopathological injury, and elevated colonic neutrophil, T-cell, and macrophage infiltration. These findings were accompanied by structural (dilated torturous lymphatic vessels) and functional (greater submucosal edema, higher immune cell burden) changes in the intestinal lymphatic vasculature. These results indicate that sufficient lymphatic clearance plays a crucial role in limiting the initiation and perpetuation of experimental colitis and those disturbances in the integrity of the intestinal lymphatic vessel network could intensify intestinal inflammation. Future therapies might be able to exploit these processes to restore and maintain adequate lymphatic clearance function in inflammatory bowel disease.

  18. Obesogenic diet-induced gut barrier dysfunction and pathobiont expansion aggravate experimental colitis.

    Directory of Open Access Journals (Sweden)

    June-Chul Lee

    Full Text Available Consumption of a typical Western diet is a risk factor for several disorders. Metabolic syndrome is the most common disease associated with intake of excess fat. However, the incidence of inflammatory bowel disease is also greater in subjects consuming a Western diet, although the mechanism of this phenomenon is not clearly understood. We examined the morphological and functional changes of the intestine, the first site contacting dietary fat, in mice fed a high-fat diet (HFD inducing obesity. Paneth cell area and production of antimicrobial peptides by Paneth cells were decreased in HFD-fed mice. Goblet cell number and secretion of mucin by goblet cells were also decreased, while intestinal permeability was increased in HFD-fed mice. HFD-fed mice were more susceptible to experimental colitis, and exhibited severe colonic inflammation, accompanied by the expansion of selected pathobionts such as Atopobium sp. and Proteobacteria. Fecal microbiota transplantation transferred the susceptibility to DSS-colitis, and antibiotic treatment abrogated colitis progression. These data suggest that an experimental HFD-induced Paneth cell dysfunction and subsequent intestinal dysbiosis characterized by pathobiont expansion can be predisposing factors to the development of inflammatory bowel disease.

  19. Intestinal Anti-inflammatory Effects of Outer Membrane Vesicles from Escherichia coli Nissle 1917 in DSS-Experimental Colitis in Mice

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    María-José Fábrega

    2017-07-01

    Full Text Available Escherichia coli Nissle 1917 (EcN is a probiotic strain with proven efficacy in inducing and maintaining remission of ulcerative colitis. However, the microbial factors that mediate these beneficial effects are not fully known. Gram-negative bacteria release outer membrane vesicles (OMVs as a direct pathway for delivering selected bacterial proteins and active compounds to the host. In fact, vesicles released by gut microbiota are emerging as key players in signaling processes in the intestinal mucosa. In the present study, the dextran sodium sulfate (DSS-induced colitis mouse model was used to investigate the potential of EcN OMVs to ameliorate mucosal injury and inflammation in the gut. The experimental protocol involved pre-treatment with OMVs for 10 days before DSS intake, and a 5-day recovery period. Oral administration of purified EcN OMVs (5 μg/day significantly reduced DSS-induced weight loss and ameliorated clinical symptoms and histological scores. OMVs treatment counteracted altered expression of cytokines and markers of intestinal barrier function. This study shows for the first time that EcN OMVs can mediate the anti-inflammatory and barrier protection effects previously reported for this probiotic in experimental colitis. Remarkably, translation of probiotics to human healthcare requires knowledge of the molecular mechanisms involved in probiotic–host interactions. Thus, OMVs, as a non-replicative bacterial form, could be explored as a new probiotic-derived therapeutic approach, with even lower risk of adverse events than probiotic administration.

  20. Adenosine Receptor Stimulation by Polydeoxyribonucleotide Improves Tissue Repair and Symptomology in Experimental Colitis.

    Science.gov (United States)

    Pallio, Giovanni; Bitto, Alessandra; Pizzino, Gabriele; Galfo, Federica; Irrera, Natasha; Squadrito, Francesco; Squadrito, Giovanni; Pallio, Socrate; Anastasi, Giuseppe P; Cutroneo, Giuseppina; Macrì, Antonio; Altavilla, Domenica

    2016-01-01

    Activation of the adenosine receptor pathway has been demonstrated to be effective in improving tissue remodeling and blunting the inflammatory response. Active colitis is characterized by an intense inflammatory reaction resulting in extensive tissue damage. Symptomatic improvement requires both control of the inflammatory process and repair and remodeling of damaged tissues. We investigated the ability of an A2A receptor agonist, polydeoxyribonucleotide (PDRN), to restore tissue structural integrity in two experimental colitis models using male Sprague-Dawley rats. In the first model, colitis was induced with a single intra-colonic instillation of dinitrobenzenesulfonic acid (DNBS), 25 mg diluted in 0.8 ml 50% ethanol. After 6 h, animals were randomized to receive either PDRN (8 mg/kg/i.p.), or PDRN + the A2A antagonist [3,7-dimethyl-1-propargylxanthine (DMPX); 10 mg/kg/i.p.], or vehicle (0.8 ml saline solution) daily. In the second model, dextran sulfate sodium (DSS) was dissolved in drinking water at a concentration of 8%. Control animals received standard drinking water. After 24 h animals were randomized to receive PDRN or PDRN+DMPX as described above. Rats were sacrificed 7 days after receiving DNBS or 5 days after DSS. In both experimental models of colitis, PDRN ameliorated the clinical symptoms and weight loss associated with disease as well as promoted the histological repair of damaged tissues. Moreover, PDRN reduced expression of inflammatory cytokines, myeloperoxidase activity, and malondialdehyde. All these effects were abolished by the concomitant administration of the A2A antagonist DMPX. Our study suggests that PDRN may represent a promising treatment for improving tissue repair during inflammatory bowel diseases.

  1. ADENOSINE RECEPTOR STIMULATION BY POLYDEOXYRIBONUCLEOTIDE IMPROVES TISSUE REPAIR AND SYMPTOMOLOGY IN EXPERIMENTAL COLITIS.

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    Giovanni Pallio

    2016-08-01

    Full Text Available Activation of the adenosine receptor pathway has been demonstrated to be effective in improving tissue remodelling and blunting the inflammatory response. Active colitis is characterized by an intense inflammatory reaction resulting in extensive tissue damage. Symptomatic improvement requires both control of the inflammatory process and repair and remodelling of damaged tissues. We investigated the ability of an A2A receptor agonist, polydeoxyribonucleotide (PDRN, to restore tissue structural integrity in two experimental colitis models using male Sprague-Dawley rats. In the first model, colitis was induced with a single intra-colonic instillation of dinitro-benzene-sulfonic acid (DNBS, 25mg diluted in 0.8ml 50% ethanol. After 6 hrs, animals were randomized to receive either PDRN (8mg/kg/i.p., or PDRN + the A2A antagonist (DMPX; 10mg/kg/i.p., or vehicle (0.8 ml saline solution daily. In the second model, dextran sodium sulphate (DSS was dissolved in drinking water at a concentration of 8%. Control animals received standard drinking water. After 24 hrs animals were randomized to receive PDRN or PDRN+DMPX as described above. Rats were sacrificed 7 days after receiving DNBS or 5 days after DSS. In both experimental models of colitis, PDRN ameliorated the clinical symptoms and weight loss associated with disease as well as promoted the histological repair of damaged tissues. Moreover, PDRN reduced expression of inflammatory cytokines, myeloperoxydase activity, and malondialdheyde. All these effects were abolished by the concomitant administration of the A2a antagonist DMPX. Our study suggests that PDRN may represent a promising treatment for improving tissue repair during inflammatory bowel diseases.

  2. Increased wall thickness using ultrasonography is associated with inflammation in an animal model of experimental colitis

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    Lied GA

    2012-10-01

    Full Text Available Gülen Arslan Lied,1 Anne Marita Milde,2 Kim Nylund,1,3 Maja Mujic,1 Tore Grimstad,1,4 Trygve Hausken,1,3 Odd Helge Gilja1,31Institute of Medicine, University of Bergen, Norway; 2Department of Biological and Medical Psychology, University of Bergen, Norway; 3National Centre for Ultrasound in Gastroenterology, Haukeland University Hospital, Bergen, Norway; 4Division of Gastroenterology, Stavanger University Hospital, Stavanger, NorwayAbstract: Experimentally induced colitis is used in animals to investigate pathophysiological mechanisms in inflammatory bowel disease. When following disease course and treatment effects, it should be possible to perform repeated measurements without harming the animals. This pilot study was performed to investigate whether transabdominal ultrasound using a clinical scanner could be used on rats to demonstrate bowel inflammation in an experimental colitis model. Colitis was induced by either 5% dextran sodium sulfate (DSS in drinking water for 7 days or a single dose of intracolonic trinitrobenzene sulfonic acid (TNBS. Using ultrasonography, wall thickness of distal colon, cecum, and small bowel was recorded prior to and after DSS, and prior to, 2, and 7 days after TNBS. Blood (tumor necrosis factor [TNF]-alpha and fecal samples (HemoFEC occult blood were taken from each group on the same days as sonography. Thereafter, rats were killed and specimens for histology were taken. Wall thickness of distal colon, not of cecum or small bowel, increased significantly after 7 days of DSS, and wall thickness of both distal colon and small bowel increased on day 2 and 7 after TNBS. TNF-alpha increased after 7 days in the latter group only. There was a significant correlation between ultrasonographic measurements and combined histology score of distal colon in the DSS group. HemoFEC was also positive in accordance with sonographic and histological features. Increased intestinal wall thickness in response to both DSS- and TNBS

  3. Cinnamon extract reduces symptoms, inflammatory mediators and mast cell markers in murine IL-10(-/-) colitis.

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    Hagenlocher, Yvonne; Hösel, Angela; Bischoff, Stephan C; Lorentz, Axel

    2016-04-01

    Inflammatory bowel disease (IBD) shows an increasing prevalence and harm in western countries. Conventional therapies are associated with bad compliance and adverse side effects. Natural substances like cinnamon extract (CE) could be an additional therapy. We found recently that CE acts anti-inflammatory on mast cells - discussed of being relevant in IBD. Here, we analysed the effects of CE on murine IL-10(-/-) colitis as model for IBD. Mice were treated 12 weeks with or without CE in drinking water. Clinical scores and disease activity index were assessed. Colonic tissue samples were analysed for infiltration, tissue damage, bowel wall thickness, expression of pro-inflammatory mediators, mast cell proteases, tight junction proteins, and NF-κB signaling. Following treatment with CE, symptoms of murine colitis as well as increased infiltration of immune cells, tissue damage and bowel wall thickness in colon tissue of IL-10(-/-) mice were diminished significantly. MIP-2, TNF, IFNγ, CCL2, CCL3, CCL4 and IL-1β as well as MC-CPA, MCP-1 and MCP-4 were strongly upregulated in IL-10(-/-) mice compared to WT, but noteworthy not in CE group. Expression of tight junction proteins was not influenced by CE. Phosphorylation of IκB was slightly down-regulated in CE treated IL-10(-/-) mice compared to IL-10(-/-) controls. In summary, CE decreases inflammatory symptoms and expression of inflammatory markers in murine IL-10(-/-) colitis. CE has no influence on tight junction proteins, but seems acting via reducing pro-inflammatory mediators and recruitment of neutrophil granulocytes probably by inhibiting NF-κB signaling. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Effect of ES products from Anisakis (Nematoda: Anisakidae) on experimentally induced colitis in adult zebrafish.

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    Haarder, S; Kania, P W; Holm, T L; von Gersdorff Jørgensen, L; Buchmann, K

    2017-10-01

    Inflammatory bowel disease (IBD) in developed countries is linked with elevated hygienic standards. One of the several factors involved in this question may be reduced exposure to the immunomodulatory effects of parasitic helminths. Several investigations on treatment of mice and humans with helminth-derived substances have supported this notion, but underlying mechanisms remain unclear. This study therefore dissects to what extent a series of immune-related genes are modulated in zebrafish with experimentally induced colitis following exposure to excretory-secretory (ES) products isolated from larval Anisakis, a widely distributed fish nematode. Adult zebrafish intrarectally exposed to the colitis-inducing agent TNBS developed severe colitis leading to 80% severe morbidity, but if co-injected (ip) with Anisakis ES products, the morbidity rate was 50% at the end of the experiment (48 hours post-exposure). Gene expression studies of TNBS-treated zebrafish showed clear upregulation of a range of genes encoding inflammatory cytokines and effector molecules and some induction of genes related to the adaptive response. A distinct innate-driven immune response was seen in both TNBS and TNBS + ES groups, but expression values were significantly depressed for several important pro-inflammatory genes in the TNBS + ES group, indicating protective mechanisms of Anisakis ES compounds on intestinal immunopathology in zebrafish. © 2017 John Wiley & Sons Ltd.

  5. Lactobacillus paracasei Reduces Intestinal Inflammation in Adoptive Transfer Mouse Model of Experimental Colitis

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    Manuel Oliveira

    2011-01-01

    Full Text Available Studies showed that specific probiotics provide therapeutic benefits in inflammatory bowel disease. In vitro evidence suggested that Lactobacillus paracasei also called ST11 (CNCM I-2116 is a potent strain with immune modulation properties. However, little is known about its capacity to alleviate inflammatory symptoms in vivo In this context, the main objective of this study was to investigate the role of ST11 on intestinal inflammation using the adoptive transfer mouse model of experimental colitis. Rag2-/- recipient mice were fed with ST11 (109 CFU/daya month prior toinduce colitis by adoptive transfer of naive T cells. One month later, in clear contrast to nonfed mice, weight loss was significantly reduced by 50% in ST11-fed mice. Further analysis of colon specimens revealed a significant reduction neutrophil infiltration and mucosal expression of IL1β, IL-6, and IL12 proinflammatory cytokines, whereas no consistent differences in expression of antibacterial peptides or tight junction proteins were observed between PBS and ST11-fed mice. All together, our results demonstrate that oral administration of ST11 was safe and had a significant preventive effect on colitis. We conclude that probiotics such as Lactobacillus paracasei harbor worthwhile in vivo immunomodulatory properties to prevent intestinal inflammation by nutritional approaches.

  6. Antepartum Antibiotic Treatment Increases Offspring Susceptibility to Experimental Colitis: A Role of the Gut Microbiota.

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    Peris Mumbi Munyaka

    Full Text Available Postnatal maturation of the immune system is largely driven by exposure to microbes, and thus the nature of intestinal colonization may be associated with development of childhood diseases that may persist into adulthood. We investigated whether antepartum antibiotic (ATB therapy can increase offspring susceptibility to experimental colitis through alteration of the gut microbiota.Pregnant C57Bl/6 mice were treated with cefazolin at 160 mg/kg body weight or with saline starting six days before due date. At 7 weeks, fecal samples were collected from male offspring after which they received 4% dextran sulfate sodium (DSS in drinking water for 5 days. Disease activity index, histology, colonic IL-6, IL-1β and serum C-reactive protein (CRP were determined. The V3-V4 region of colonic and fecal bacterial 16S rRNA was sequenced. Alpha-, beta-diversity and differences at the phylum and genus levels were determined, while functional pathways of classified bacteria were predicted.ATB influenced fecal bacterial composition and hence bacterial functional pathways before induction of colitis. After induction of colitis, ATB increased onset of clinical disease, histologic score, and colonic IL-6. In addition, ATB decreased fecal microbial richness, changed fecal and colon microbial composition, which was accompanied by a modification of microbial functional pathways. Also, several taxa were associated with ATB at lower taxonomical levels.The results support the hypothesis that antepartum antibiotics modulate offspring intestinal bacterial colonization and increase susceptibility to develop colonic inflammation in a murine model of colitis, and may guide future interventions to restore physiologic intestinal colonization in offspring born by antibiotic-exposed mothers.

  7. Effect of piperine on inhibition of FFA induced TLR4 mediated inflammation and amelioration of acetic acid induced ulcerative colitis in mice.

    Science.gov (United States)

    Gupta, Rohit A; Motiwala, Meha N; Dumore, Nitin G; Danao, Kishor R; Ganjare, Anjali B

    2015-04-22

    Piperine, a main component of Piper longum Linn. and Piper nigrum Linn., is a plant alkaloid with a long history of medicinal use. Piperine exhibits antidepressant, hepatoprotective, anti-metastatic, anti-thyroid, immunomodulatory, antitumor and anti-inflammatory activities, However its therapeutic potential in amelioration of ulcerative colitis and the underlying mechanism for anti-inflammatory activity remains unknown.The objective of the present investigation was to unravel the therapeutic potential of piperine on amelioration of IBD using acetic acid induced experimental animal model for ulcerative colitis and to determine the role of TLR4 receptor in signalling pathway of inflammatory gene expression in ulcerative colitis. We induced colitis using acetic acid (150µl of 5% once, intrarectally) in mice and estimated disease activity index (DAI), which took into account weight loss, stool consistency, and occult/gross bleeding. Colon length, spleen weights, ulcer area and ulcer index were measured; histological changes were observed by H&E staining. Effect of piperine on various antioxidant parameter of mice colon such as tissue myeloperoxidase (MPO) accumulation, SOD concentrations, reduced GSH and lipid peroxidation were determined. Pro-inflammatory mediators, namely, nitric oxide (NO), tumour necrosis factor-α (TNF-α) were determined by a TNF-α ELISA kit obtained from Thermo fisher scientific India Pvt. Ltd. Effect of piperine on haematological parameters of mice in acetic acid induced IBD was also determined which involves the estimation of FFA using a commercial free fatty acid fluorometric assay kit. Piperine significantly attenuated acetic acid induced DAI score which implies that it suppresses weight loss, diarrhoea, gross bleeding and infiltration of immune cells. Piperine administration also effectively and dose dependently prevented shortening of colon length and enlargement of spleen size. Histological examination indicated that piperine reduces

  8. Preparation and investigation of P28GST-loaded PLGA microparticles for immunomodulation of experimental colitis.

    Science.gov (United States)

    Thi, T H Hoang; Priemel, P A; Karrout, Y; Driss, V; Delbeke, M; Dendooven, A; Flament, M P; Capron, M; Siepmann, J

    2017-11-25

    The aim of this work was to prepare and characterize (in vitro and in vivo) PLGA-based microparticles loaded with an enzymatic protein derived from the helminth parasite Schistosoma haematobium: glutathione S-transferase P28GST (P28GST). This protein is not only a promising candidate vaccine against schistosomiasis, it also exhibits interesting immunomodulating effects, which can be helpful for the regulation of inflammatory diseases. Helminths express a regulatory role on intestinal inflammation, and immunization by P28GST has recently been shown to be as efficient as infection to reduce inflammation in a murine colitis model. As an alternative to the combination with a classical adjuvant, long acting P28GST microparticles were prepared in order to induce colitis prevention. PLGA was used as biodegradable and biocompatible matrix former, and a W/O/W emulsion/solvent extraction technique applied to prepare different types of microparticles. The effects of key formulation and processing parameters (e.g., the polymer molecular weight, drug loading, W/O/W phase volumes and stirring rates of the primary/secondary emulsions) on the systems' performance were studied. Microparticles providing about constant P28GST release during several weeks were selected and their effects in an experimental model of colitis evaluated. Mice received P28GST-loaded or P28GST-free PLGA microparticles (s.c.) on Day 0, and optionally also on Days 14 and 28. Colitis was induced on Day 35, the animals were sacrificed on Day 37. Interestingly, the Wallace score (being a measure of the severity of the inflammation) was significantly lower in mice treated with P28GST microparticles compared to placebo after 1 or 3 injections. As immunogenicity markers, increased anti-P28GST IgG levels were detected after three P28GST PLGA microparticle injections, but not in the control groups. Thus, the proposed microparticles offer an interesting potential for the preventive treatment of experimental colitis

  9. 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. ...

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

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    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.

  11. Preventive effect of the microalga Chlamydomonas debaryana on the acute phase of experimental colitis in rats.

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    Avila-Román, Javier; Talero, Elena; Alcaide, Antonio; Reyes, Carolina de Los; Zubía, Eva; García-Mauriño, Sofía; Motilva, Virginia

    2014-10-14

    Inflammatory bowel diseases (IBD) are characterised by chronic uncontrolled inflammation of intestinal mucosa. Diet and nutritional factors have emerged as possible interventions for IBD. Microalgae are rich sources of n-3 PUFA and derived oxylipins. Oxylipins are lipid mediators involved in the resolution of many inflammatory disorders. The aim of the present study was to investigate the effects of the oxylipin-containing biomass of the microalga Chlamydomonas debaryana and its major oxylipin constituent, (9Z,11E,13S,15Z)-13-hydroxyoctadeca-9,11,15-trienoic acid ((13S)-HOTE), on acute 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats. Lyophilised microalgal biomass and (13S)-HOTE were administered by oral route 48, 24 and 1 h before the induction of colitis and 24 h later, and the rats were killed after 48 h. The treatment with the lyophilised microalga and (13S)-HOTE improved body-weight loss and colon shortening, as well as attenuated the extent of colonic damage and increased mucus production. Cellular neutrophil infiltration, with the subsequent increase in myeloperoxidase levels induced by TNBS, were also reduced after the administration of the lyophilised microalga or (13S)-HOTE. The anti-inflammatory effects of these treatments were confirmed by the inhibition of colonic TNF-α production. Moreover, lyophilised microalga or (13S)-HOTE down-regulated cyclo-oxygenase-2 and inducible nitric oxide synthase expression. The present study was the first to show the prophylactic effects of a lyophilised biomass sample of the microalga C. debaryana and the oxylipin (13S)-HOTE on TNBS-induced acute colitis in rats. Our findings suggest that the microalga C. debaryana or derived oxylipins could be used as nutraceuticals in the treatment of the active phase of IBD.

  12. Protein tyrosine phosphatase 1B deficiency ameliorates murine experimental colitis via the expansion of myeloid-derived suppressor cells.

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    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.

  13. Role of Eosinophils and Tumor Necrosis Factor Alpha in Interleukin-25-Mediated Protection from Amebic Colitis

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    Zannatun Noor

    2017-02-01

    Full Text Available The parasite Entamoeba histolytica is a cause of diarrhea in infants in low-income countries. Previously, it was shown that tumor necrosis factor alpha (TNF-α production was associated with increased risk of E. histolytica diarrhea in children. Interleukin-25 (IL-25 is a cytokine that is produced by intestinal epithelial cells that has a role in maintenance of gut barrier function and inhibition of TNF-α production. IL-25 expression was decreased in humans and in the mouse model of amebic colitis. Repletion of IL-25 blocked E. histolytica infection and barrier disruption in mice, increased gut eosinophils, and suppressed colonic TNF-α. Depletion of eosinophils with anti-Siglec-F antibody prevented IL-25-mediated protection. In contrast, depletion of TNF-α resulted in resistance to amebic infection. We concluded that IL-25 provides protection from amebiasis, which is dependent upon intestinal eosinophils and suppression of TNF-α.

  14. Cerebroside D, a glycoceramide compound, improves experimental colitis in mice with multiple targets against activated T lymphocytes

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    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.

  15. Vancomycin pre-treatment impairs tissue healing in experimental colitis: Importance of innate lymphoid cells.

    Science.gov (United States)

    Zhao, Di; Cai, Chenwen; Zheng, Qing; Jin, Shuang; Song, Dongjuan; Shen, Jun; Ran, Zhihua

    2017-01-29

    The interplay between luminal microbes and innate immunity during colonic epithelial repair has been well noted. At the same time, antibiotic has widely been used during flare-ups of ulcerative colitis. The possible effects of luminal microbiota disruption caused by antibiotics usage on epithelial repairing have been scarcely discussed. Innate lymphoid cells (ILCs) embedded in the lamina propria can be modulated by gut microbes, resulting in altered colonic IL-22/pSTAT3 levels, which is considered a prominent molecular axis in tissue repairing after epithelium damage. This study aimed to investigate whether antibiotics could interfere with ILCs-dependent tissue repair. Dextran sodium sulfate (DSS)-induced colitis was established in mice pre-treated with reagent of different antibiotic spectrum. Both morphological and molecular markers of tissue repair after DSS cessation were detected. ILCs population and function status were also recorded. Further attention was paid to the response of dendritic cells after antibiotics treatment, which were claimed to regulate colonic ILC3s in an IL-23 dependent way. Using of vancomycin resulted in delayed tissue repairing after experimental colitis. Both colonic IL-22/pSTAT3 axis and ILC3 population were found decreased in this situation. Vancomycin treatment diminished the upstream IL-23 and producer dendritic cell population. The reduced dendritic cell number may due to inadequate chemokines and colony-stimulating factors supply. Presence of vancomycin-sensitive microbiota is required for the maturation of ILC3-activating dendritic cells hence maintain the sufficient IL-22/pSTAT3 level in the colon during tissue healing. Manipulation of colonic microbiota may help achieve colonic mucosal healing post inflammation and injury. Copyright © 2016. Published by Elsevier Inc.

  16. Effect of mesalazine, metronidazole and gentamicin on bacterial translocation in experimental colitis.

    Science.gov (United States)

    Yigitler, Cengizhan; Gulec, Bulent; Aydogan, Hakan; Ozcan, Ayhan; Kilinc, Metin; Yigit, Taner; Kozak, Orhan; Pekcan, Mesut

    2004-10-01

    changes in experimental colitis. Metronidazole and gentamicin combination given intraperitoneally was more effective than topical mesalazine in decreasing bacterial translocation.

  17. Membrane-bound Dickkopf-1 in Foxp3+ regulatory T cells suppresses T-cell-mediated autoimmune colitis.

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    Chae, Wook-Jin; Park, Jong-Hyun; Henegariu, Octavian; Yilmaz, Saliha; Hao, Liming; Bothwell, Alfred L M

    2017-10-01

    Induction of tolerance is a key mechanism to maintain or to restore immunological homeostasis. Here we show that Foxp3+ regulatory T (Treg) cells use Dickkopf-1 (DKK-1) to regulate T-cell-mediated tolerance in the T-cell-mediated autoimmune colitis model. Treg cells from DKK-1 hypomorphic doubleridge mice failed to control CD4+ T-cell proliferation, resulting in CD4 T-cell-mediated autoimmune colitis. Thymus-derived Treg cells showed a robust expression of DKK-1 but not in naive or effector CD4 T cells. DKK-1 expression in Foxp3+ Treg cells was further increased upon T-cell receptor stimulation in vitro and in vivo. Interestingly, Foxp3+ Treg cells expressed DKK-1 in the cell membrane and the functional inhibition of DKK-1 using DKK-1 monoclonal antibody abrogated the suppressor function of Foxp3+ Treg cells. DKK-1 expression was dependent on de novo protein synthesis and regulated by the mitogen-activated protein kinase pathway but not by the canonical Wnt pathway. Taken together, our results highlight membrane-bound DKK-1 as a novel Treg-derived mediator to maintain immunological tolerance in T-cell-mediated autoimmune colitis. © 2017 The Authors. Immunology Published by John Wiley & Sons Ltd.

  18. Pseudomembranous collagenous colitis.

    Science.gov (United States)

    Yuan, Shan; Reyes, Victoria; Bronner, Mary P

    2003-10-01

    The classic clinical and histologic features of collagenous colitis are well characterized; however, the acute or neutrophilic inflammatory changes that may accompany this entity are less well established. In this report of 10 patients, we describe the first series of pseudomembranous collagenous colitis. Because superimposed Clostridium difficile infection was only demonstrated in one patient and no other causes of pseudomembranous colitis were evident in the remaining nine patients, we conclude that pseudomembranes are part of the spectrum of collagenous colitis itself. This case series illustrates the importance of searching for collagenous colitis in the evaluation of pseudomembranous colitis. At the same time, superimposed infectious or ischemic etiologies need to be excluded clinically in any patient with superimposed pseudomembranes. The existence of pseudomembranes in collagenous colitis also lends support to the hypothesis that toxin- and/or ischemia-mediated injury may be involved in the pathogenesis of collagenous colitis.

  19. Dietary Agents and Phytochemicals in the Prevention and Treatment of Experimental Ulcerative Colitis

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    Arpit Saxena

    2014-10-01

    Full Text Available Inflammatory bowel diseases (IBDs, consisting mainly of ulcerative colitis (UC and Crohn's disease (CD, are important immune-mediated diseases of the gastrointestinal tract. The etiology of the disease includes environmental and genetic factors. Its management presents a constant challenge for gastroenterologists and conventional surgeon. 5-Amninosalicylates, antibiotics, steroids, and immune modulators have been used to reduce the symptoms and for maintenance of remission. Unfortunately, long-term usage of these agents has been found to lead to severe toxicities, which are deterrent to the users. Pre-clinical studies carried out in the recent past have shown that certain dietary agents, spices, oils, and dietary phytochemicals that are consumed regularly possess beneficial effects in preventing/ameliorating UC. For the first time, this review addresses the use of these dietary agents and spices in the treatment and prevention of IBD and also emphasizes on the mechanisms responsible for their effects.

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

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    Baoshan Liu

    2016-01-01

    Full Text Available 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.

  1. Modulation of Gut Microbiome Composition and Function in Experimental Colitis Treated with Sulfasalazine.

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    Zheng, Haihui; Chen, Mingyi; Li, Yuan; Wang, Yuanyuan; Wei, Lin; Liao, Ziqiong; Wang, Mengxia; Ma, Fangli; Liao, Qiongfeng; Xie, Zhiyong

    2017-01-01

    Inflammatory bowel disease (IBD) results from alterations in intestinal flora and the immune system. Sulfasalazine (SASP) is a sulfa antimicrobial used to treat IBD in clinic for years. However, how SASP affects gut microbes and its potential functions remains unclear. To investigate the relationships of SASP, IBD, and gut microbiome, we used 2,4,6-trinitrobenzenesulfonic acid (TNBS) to induce experimental colitis in rats, and analyzed the microbiota in the fecal samples, which come from the control group (treated with ethanol + saline), the model group (treated with TNBS-ethanol + saline) and the SASP group (treated with TNBS-ethanol + SASP), with 16S gene sequencing and followed up a subset sample using shotgun sequencing. The study found that SASP treatment could not only restore the TNBS-induced gut dysbiosis, which was proved by the increasing amount of SCFAs-producing bacteria and lactic acid-producing bacteria as well as the decreasing amount of Proteobacteria, but also modulate the dysregulated function of the TNBS-induced colitis to resemble that of the control group, including an increased capacity for basic metabolism (carbohydrate metabolism, citrate cycle) and a decrease in the oxidative stress (riboflavin, sulfur, cysteine) as well as bacterial pathogenesis (cell motility and secretion, bacterial motility proteins, flagellar assembly). Moreover, a higher proportion of Mycoplasma was observed in the SASP group, which may associate with infertility. In all, the study provides insight into specific microbial clades and pathways linked with SASP treatment to elaborate the mechanism for treatment of IBD.

  2. COMPARISON OF SELECTIVE AND NON SELECTIVE CYCLO-OXYGENASE 2 INHIBITORS IN EXPERIMENTAL COLITIS EXACERBATION: role of leukotriene B4 and superoxide dismutase

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    José Wander BREGANÓ

    2014-09-01

    Full Text Available Context Nonsteroidal anti-inflammatory drugs are considered one of the most important causes of reactivation of inflammatory bowel disease. With regard to selective cyclo-oxygenase 2 inhibitors, the results are controversial in experimental colitis as well as in human studies. Objectives The aim this study is to compare nonsteroidal anti-inflammatory drugs effects, selective and non selective cyclo-oxygenase 2 inhibitors, in experimental colitis and contribute to the understanding of the mechanisms which nonsteroidal anti-inflammatory drugs provoke colitis exacerbation. Methods Six groups of rats: without colitis, with colitis, and colitis treated with celecoxib, ketoprofen, indometacin or diclofenac. Survival rates, hemoglobin, plasmatic albumin, colonic tissue of interleukin-1ß, interleukin-6, tumor necrosis factor alpha, prostaglandin E2, catalase, superoxide dismutase, thiobarbituric acid-reactive substances, chemiluminescence induced by tert-butil hydroperoxides, and tissue and plasmatic leukotriene B4 were determined. Results The groups treated with diclofenac or indometacin presented lower survival rates, hemoglobin and albumin, higher tissue and plasmatic leukotriene B4 and tissue superoxide dismutase than the group treated with celecoxib. Ketoprofen presented an intermediary behavior between diclofenac/indometacin and celecoxib, concerning to survival rate and albumin. The groups without colitis, with colitis and with colitis treated with celecoxib showed leukotriene B4 and superoxide dismutase lower levels than the groups treated with nonselective cyclo-oxygenase 2 inhibitors. Conclusions Diclofenac and indometacin presented the highest degree of induced colitis exacerbation with nonsteroidal anti-inflammatory drugs, celecoxib did not show colitis exacerbation, and ketoprofen presented an intermediary behavior between diclofenac/indometacin and celecoxib. These results suggest that leukotriene B4 and superoxide dismutase can be

  3. Extracellular Vesicles Derived from Bone Marrow Mesenchymal Stem Cells Protect against Experimental Colitis via Attenuating Colon Inflammation, Oxidative Stress and Apoptosis.

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    Yang, Jia; Liu, Xing-Xing; Fan, Heng; Tang, Qing; Shou, Zhe-Xing; Zuo, Dong-Mei; Zou, Zhou; Xu, Meng; Chen, Qian-Yun; Peng, Ying; Deng, Shuang-Jiao; Liu, Yu-Jin

    2015-01-01

    The administration of bone mesenchymal stem cells (BMSCs) could reverse experimental colitis, and the predominant mechanism in tissue repair seems to be related to their paracrine activity. BMSCs derived extracellular vesicles (BMSC-EVs), including mcirovesicles and exosomes, containing diverse proteins, mRNAs and micro-RNAs, mediating various biological functions, might be a main paracrine mechanism for stem cell to injured cell communication. We aimed to investigate the potential alleviating effects of BMSC-EVs in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis model. Intravenous injection of BMSC-EVs attenuated the severity of colitis as evidenced by decrease of disease activity index (DAI) and histological colonic damage. In inflammation response, the BMSC-EVs treatment significantly reduced both the mRNA and protein levels of nuclear factor kappaBp65 (NF-κBp65), tumor necrosis factor-alpha (TNF-α), induciblenitric oxidesynthase (iNOS) and cyclooxygenase-2 (COX-2) in injured colon. Additionally, the BMSC-EVs injection resulted in a markedly decrease in interleukin-1β (IL-1β) and an increase in interleukin-10 (IL-10) expression. Therapeutic effect of BMSC-EVs associated with suppression of oxidative perturbations was manifested by a decrease in the activity of myeloperoxidase (MPO) and Malondialdehyde (MDA), as well as an increase in superoxide dismutase (SOD) and glutathione (GSH). BMSC-EVs also suppressed the apoptosis via reducing the cleavage of caspase-3, caspase-8 and caspase-9 in colitis rats. Data obtained indicated that the beneficial effects of BMSC-EVs were due to the down regulation of pro-inflammatory cytokines levels, inhibition of NF-κBp65 signal transduction pathways, modulation of anti-oxidant/ oxidant balance, and moderation of the occurrence of apoptosis.

  4. Extracellular Vesicles Derived from Bone Marrow Mesenchymal Stem Cells Protect against Experimental Colitis via Attenuating Colon Inflammation, Oxidative Stress and Apoptosis.

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    Jia Yang

    Full Text Available The administration of bone mesenchymal stem cells (BMSCs could reverse experimental colitis, and the predominant mechanism in tissue repair seems to be related to their paracrine activity. BMSCs derived extracellular vesicles (BMSC-EVs, including mcirovesicles and exosomes, containing diverse proteins, mRNAs and micro-RNAs, mediating various biological functions, might be a main paracrine mechanism for stem cell to injured cell communication. We aimed to investigate the potential alleviating effects of BMSC-EVs in 2,4,6-trinitrobenzene sulfonic acid (TNBS-induced colitis model. Intravenous injection of BMSC-EVs attenuated the severity of colitis as evidenced by decrease of disease activity index (DAI and histological colonic damage. In inflammation response, the BMSC-EVs treatment significantly reduced both the mRNA and protein levels of nuclear factor kappaBp65 (NF-κBp65, tumor necrosis factor-alpha (TNF-α, induciblenitric oxidesynthase (iNOS and cyclooxygenase-2 (COX-2 in injured colon. Additionally, the BMSC-EVs injection resulted in a markedly decrease in interleukin-1β (IL-1β and an increase in interleukin-10 (IL-10 expression. Therapeutic effect of BMSC-EVs associated with suppression of oxidative perturbations was manifested by a decrease in the activity of myeloperoxidase (MPO and Malondialdehyde (MDA, as well as an increase in superoxide dismutase (SOD and glutathione (GSH. BMSC-EVs also suppressed the apoptosis via reducing the cleavage of caspase-3, caspase-8 and caspase-9 in colitis rats. Data obtained indicated that the beneficial effects of BMSC-EVs were due to the down regulation of pro-inflammatory cytokines levels, inhibition of NF-κBp65 signal transduction pathways, modulation of anti-oxidant/ oxidant balance, and moderation of the occurrence of apoptosis.

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

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

    2016-01-01

    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+CD64lowLy6C+ 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. PMID:26349655

  6. Cinnamon extract suppresses experimental colitis through modulation of antigen-presenting cells.

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    Kwon, Ho-Keun; Hwang, Ji-Sun; Lee, Choong-Gu; So, Jae-Seon; Sahoo, Anupama; Im, Chang-Rok; Jeon, Won Kyung; Ko, Byoung Seob; Lee, Sung Haeng; Park, Zee Yong; Im, Sin-Hyeog

    2011-02-28

    To investigate the anti-inflammatory effects of cinnamon extract and elucidate its mechanisms for targeting the function of antigen presenting cells. Cinnamon extract was used to treat murine macrophage cell line (Raw 264.7), mouse primary antigen-presenting cells (APCs, MHCII(+)) and CD11c(+) dendritic cells to analyze the effects of cinnamon extract on APC function. The mechanisms of action of cinnamon extract on APCs were investigated by analyzing cytokine production, and expression of MHC antigens and co-stimulatory molecules by quantitative real-time PCR and flow cytometry. In addition, the effect of cinnamon extract on antigen presentation capacity and APC-dependent T-cell differentiation were analyzed by [H(3)]-thymidine incorporation and cytokine analysis, respectively. To confirm the anti-inflammatory effects of cinnamon extract in vivo, cinnamon or PBS was orally administered to mice for 20 d followed by induction of experimental colitis with 2,4,6 trinitrobenzenesulfonic acid. The protective effects of cinnamon extract against experimental colitis were measured by checking clinical symptoms, histological analysis and cytokine expression profiles in inflamed tissue. Treatment with cinnamon extract inhibited maturation of MHCII(+) APCs or CD11c(+) dendritic cells (DCs) by suppressing expression of co-stimulatory molecules (B7.1, B7.2, ICOS-L), MHCII and cyclooxygenase (COX)-2. Cinnamon extract induced regulatory DCs (rDCs) that produce low levels of pro-inflammatory cytokines [interleukin (IL)-1β, IL-6, IL-12, interferon (IFN)-γ and tumor necrosis factor (TNF)-α] while expressing high levels of immunoregulatory cytokines (IL-10 and transforming growth factor-β). In addition, rDCs generated by cinnamon extract inhibited APC-dependent T-cell proliferation, and converted CD4(+) T cells into IL-10(high) CD4(+) T cells. Furthermore, oral administration of cinnamon extract inhibited development and progression of intestinal colitis by inhibiting expression

  7. Potential usefulness of methyl gallate in the treatment of experimental colitis.

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    Anzoise, María Laura; Basso, Angeles Rodríguez; Del Mauro, Julieta Sofía; Carranza, Andrea; Ordieres, Graciela López; Gorzalczany, Susana

    2017-11-07

    Methyl gallate is a gallotannin widely distributed in nature. Previous studies have demonstrated its antioxidant, anti-inflammatory, antimicrobial and anti-tumor activities. In the present study, the activity of methyl gallate on experimental models of inflammatory bowel disease has been investigated. Experimental colitis was induced in Sprague-Dawley rats through the intracolonic instillation of an acetic acid solution (2 mL, 4% v/v). Methyl gallate (100 and 300 mg/kg, p.o.) and the reference drug mesalazine (100 mg/kg, p.o.) were tested. Methyl gallate induced a significant reduction in the colon weight/length ratio and macroscopic lesion score. Besides, the malondialdehyde content and the GSSG/GSH ratio were remarkably decreased. Furthermore, the administration of methyl gallate reduced the expression of COX 2 , IL-6, TNFα and the severity of microscopic tissue damage induced by acetic acid, while the mean goblet cell density was significantly higher in both the group treated with methyl gallate and the one treated with mesalazine, in comparison with untreated animals. The Na + K + ATPase pump activity was recovered in treated groups (control: 827.2 ± 59.6, colitis: 311.6 ± 54.8, methyl gallate 100 mg/kg: 642.2 ± 175.0, methyl gallate 300 mg/kg: 809.7 ± 100.6, mesalazine: 525.3 ± 81.7). Methyl gallate was also found to induce a significant reduction in the castor oil-induced intestinal motility in Swiss mice, decreasing the peristalsis by 74.5 and 58.82% at 100 and 300 mg/kg p.o., respectively. This compound also antagonized the jejunum contractions induced by Ach and CaCl 2 . This study demonstrates that methyl gallate exerts beneficial effects in a preclinical model of intestinal disorders.

  8. 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.

  9. Ursodeoxycholic Acid and Its Taurine- or Glycine-Conjugated Species Reduce Colitogenic Dysbiosis and Equally Suppress Experimental Colitis in Mice.

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    Van den Bossche, Lien; Hindryckx, Pieter; Devisscher, Lindsey; Devriese, Sarah; Van Welden, Sophie; Holvoet, Tom; Vilchez-Vargas, Ramiro; Vital, Marius; Pieper, Dietmar H; Vanden Bussche, Julie; Vanhaecke, Lynn; Van de Wiele, Tom; De Vos, Martine; Laukens, Debby

    2017-04-01

    The promising results seen in studies of secondary bile acids in experimental colitis suggest that they may represent an attractive and safe class of drugs for the treatment of inflammatory bowel diseases (IBD). However, the exact mechanism by which bile acid therapy confers protection from colitogenesis is currently unknown. Since the gut microbiota plays a crucial role in the pathogenesis of IBD, and exogenous bile acid administration may affect the community structure of the microbiota, we examined the impact of the secondary bile acid ursodeoxycholic acid (UDCA) and its taurine or glycine conjugates on the fecal microbial community structure during experimental colitis. Daily oral administration of UDCA, tauroursodeoxycholic acid (TUDCA), or glycoursodeoxycholic acid (GUDCA) equally lowered the severity of dextran sodium sulfate-induced colitis in mice, as evidenced by reduced body weight loss, colonic shortening, and expression of inflammatory cytokines. Illumina sequencing demonstrated that bile acid therapy during colitis did not restore fecal bacterial richness and diversity. However, bile acid therapy normalized the colitis-associated increased ratio of Firmicutes to Bacteroidetes Interestingly, administration of bile acids prevented the loss of Clostridium cluster XIVa and increased the abundance of Akkermansia muciniphila, bacterial species known to be particularly decreased in IBD patients. We conclude that UDCA, which is an FDA-approved drug for cholestatic liver disorders, could be an attractive treatment option to reduce dysbiosis and ameliorate inflammation in human IBD.IMPORTANCE Secondary bile acids are emerging as attractive candidates for the treatment of inflammatory bowel disease. Although bile acids may affect the intestinal microbial community structure, which significantly contributes to the course of these inflammatory disorders, the impact of bile acid therapy on the fecal microbiota during colitis has not yet been considered. Here, we

  10. 3-(3-Pyridylmethylidene-2-indolinone Reduces the Severity of Colonic Injury in a Murine Model of Experimental Colitis

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    Kun-Ping Wang

    2015-01-01

    Full Text Available Nrf2 is the key transcription factor regulating the antioxidant response which is crucial for cytoprotection against extracellular stresses. Numerous in vivo studies indicate that Nrf2 plays a protective role in anti-inflammatory response. 3-(3-Pyridylmethylidene-2-indolinone (PMID is a synthesized derivative of 2-indolinone compounds. Our previous study suggested that PMID induces the activation of Nrf2/ARE pathway, then protecting against oxidative stress-mediated cell death. However, little is known regarding the anti-inflammatory properties of PMID in severe inflammatory phenotypes. In the present study we determined if PMID treatment protects mice from dextran sodium sulphate- (DSS- induced colitis. The result suggests that treatment with PMID prior to colitis induction significantly reduced body weight loss, shortened colon length, and decreased disease activity index compared to control mice. Histopathological analysis of the colon revealed attenuated inflammation in PMID pretreated animals. The levels of inflammatory markers in colon tissue and serum were reduced associated with inhibition of NF-κB activation. The expression levels of Nrf2-dependent genes such as HO-1, NQO1, and Nrf2 were increased in PMID pretreated mice. However, PMID pretreatment did not prevent DSS-induced colitis in Nrf2 knockout mice. These data indicate that PMID pretreatment in mice confers protection against DSS-induced colitis in Nrf2-dependent manner, suggesting a potential role of PMID in anti-inflammatory response.

  11. Stability of Reference Genes for Messenger RNA Quantification by Real-Time PCR in Mouse Dextran Sodium Sulfate Experimental Colitis.

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    Nour Eissa

    Full Text Available Many animal models have been developed to characterize the complexity of colonic inflammation. In dextran sodium sulfate (DSS experimental colitis in mice the choice of reference genes is critical for accurate quantification of target genes using quantitative real time PCR (RT-qPCR. No studies have addressed the performance of reference genes in mice DSS-experimental colitis. This study aimed to determine the stability of reference genes expression (RGE in DSS-experimental murine colitis.Colitis was induced in male C57BL/6 mice using DSS5% for 5 days, control group received water. RNA was extracted from inflamed and non-inflamed colon. Using RT-qPCR, comparative analysis of 13 RGE was performed according to predefined criteria and relative colonic TNF-α and IL-1β gene expression was determined by calculating the difference in the threshold cycle.Colitis significantly altered the stability of mucosal RGE. Commonly used glyceraldehyde-3-phosphate dehydrogenase (Gapdh, β-actin (Actb, or β2-microglobulin (β2m showed the highest variability within the inflamed and control groups. Conversely, TATA-box-binding protein (Tbp and eukaryotic translation elongation factor 2 (Eef2 were not affected by inflammation and were the most stable genes. Normalization of colonic TNF-α and IL-1β mRNA levels was dependent on the reference gene used. Depending on the genes used to normalize the data, statistical significance varied from significant when TBP / Eef2 were used to non-significant when Gapdh, Actb or β2m were used.This study highlights the appropriate choice of RGE to ensure adequate normalization of RT-qPCR data when using this model. Suboptimal RGE may explain controversial results from published studies. We recommend using Tbp and Eef2 instead of Gapdh, Actb or β2m as reference genes.

  12. Effects of Malva sylvestris and Its Isolated Polysaccharide on Experimental Ulcerative Colitis in Rats.

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    Hamedi, Azadeh; Rezaei, Hossein; Azarpira, Negar; Jafarpour, Mehrnaz; Ahmadi, Fatemeh

    2016-01-01

    Malva sylvestris is an edible plant that is consumed as a herbal supplement for its antiulcer and colon cleansing properties in traditional Persian medicine. This study was designed to evaluate its effects on ulcerative colitis, which is a chronic gastrointestinal inflammation. Colitis was induced by rectal instillation of acetic acid solution. Rats in different groups received aqueous, n-hexane, or ethanolic fractions of the plant before induction of colitis. Isolated polysaccharide of plant was also tested in 2 groups before and after induction of colitis. Macroscopic and microscopic evaluation of colitis showed that the aqueous fraction was very effective in preventing the inflammation and efficacy was lower for ethanolic and n-hexane fractions. Polysaccharide was effective in reducing signs of inflammation, especially as pretreatment. These beneficial effects provide evidences that this plant can be suggested for patients with this disease to improve their health condition or to reduce adverse effects of their medication. © The Author(s) 2015.

  13. Nutrition and ulcerative colitis.

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    Burke, A; Lichtenstein, G R; Rombeau, J L

    1997-03-01

    The role of diet in the aetiology and pathogenesis of ulcerative colitis (UC) remains uncertain. Impaired utilization by colonocytes of butyrate, a product of bacterial fermentation of dietary carbohydrates escaping digestion, may be important. Sulphur-fermenting bacteria may be involved in this impaired utilization. Oxidative stress probably mediates tissue injury but is probably not of causative importance. Patients with UC are prone to malnutrition and its detrimental effects. However, there is no role for total parenteral nutrition and bowel rest as primary therapy for UC. The maintenance of adequate nutrition is very important, particularly in the peri-operative patient. In the absence of massive bleeding, perforation, toxic megacolon or obstruction, enteral rather than parenteral nutrition should be the mode of choice. Nutrients may be beneficial as adjuvant therapy. Butyrate enemas have improved patients with otherwise recalcitrant distal colitis in small studies. Non-cellulose fibre supplements are of benefit in rats with experimental colitis. Eicosapentaenoic acid in fish oil has a steroid-sparing effect which, although modest, is important, particularly in terms of reducing the risk of osteoporosis, but it seems to have no role in the patient with inactive disease. gamma-Linolenic acid and anti-oxidants also are showing promise. Nutrients may also modify the increased risk of colorectal carcinoma. Oxidative stress can damage tissue DNA but there are no data published at present on possible protection from oral anti-oxidants. Butyrate protects against experimental carcinogenesis in rats with experimental colitis. Folate supplementation is weakly associated with decreased incidence of cancer in UC patients when assessed retrospectively. Vigilance should be maintained for increased micronutrient requirements and supplements given as appropriate. Calcium and low-dose vitamin D should be given to patients on long-term steroids and folate to those on

  14. Protective effects of Aegle marmelos fruit pulp on 2,4,6-trinitrobenzene sulfonic acid-induced experimental colitis.

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    Ghatule, Rohit R; Gautam, Manish K; Goel, Shalini; Singh, Amit; Joshi, Vinod K; Goel, Raj K

    2014-01-01

    Aegle marmelos (AM) fruit has been advocated in indigenous system of medicine for the treatment of various gastrointestinal disorders, fever, asthma, inflammations, febrile delirium, acute bronchitis, snakebite, epilepsy, leprosy, myalgia, smallpox, leucoderma, mental illnesses, sores, swelling, thirst, thyroid disorders, tumours and upper respiratory tract infections. The objective of this study was to study the curative effect of 50% ethanol extract of dried fruit pulp of AM (AME) against 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis. AME (200 mg/kg) was administered orally, once daily for 14 days after TNBS-induced colitis. Rats were given intracolonic normal saline or TNBS alone or TNBS plus oral AME. AME was studied for its in vitro antibacterial activity against Gram-negative intestinal bacteria and on TNBS-induced changes in colonic damage, weight and adhesions (macroscopic and microscopic), diarrhea, body weight and colonic levels of free radicals (nitric oxide and lipid peroxidation), antioxidants (superoxide dismutase, catalase and reduced glutathione) and pro-inflammatory marker (myeloperoxidase [MPO]) in rats. AME showed antibacterial activity against intestinal pathogens and decreased colonic mucosal damage and inflammation, diarrhea, colonic free radicals and MPO and enhanced body weight and colonic antioxidants level affected by TNBS. The effects of AME on the above parameters were comparable with sulfasalazine, a known colitis protective drug (100 mg/kg, oral). AME shows curative effects against TNBS-induced colitis by its antibacterial activity and promoting colonic antioxidants and reducing free radicals and MPO-induced colonic damage.

  15. Probiotic yeasts: anti-inflammatory potential of various non-pathogenic strains in experimental colitis in mice.

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    Foligné, Benoît; Dewulf, Joëlle; Vandekerckove, Pascal; Pignède, Georges; Pot, Bruno

    2010-05-07

    To evaluate the in vitro immunomodulation capacity of various non-pathogenic yeast strains and to investigate the ability of some of these food grade yeasts to prevent experimental colitis in mice. In vitro immunomodulation was assessed by measuring cytokines [interleukin (IL)-12p70, IL-10, tumor necrosis factor and interferon gamma] released by human peripheral blood mononuclear cells after 24 h stimulation with 6 live yeast strains (Saccharomyces ssp.) and with bacterial reference strains. A murine model of acute 2-4-6-trinitrobenzene sulfonic acid (TNBS)-colitis was next used to evaluate the distinct prophylactic protective capacities of three yeast strains compared with the performance of prednisolone treatment. The six yeast strains all showed similar non-discriminating anti-inflammatory potential when tested on immunocompetent cells in vitro. However, although they exhibited similar colonization patterns in vivo, some yeast strains showed significant anti-inflammatory activities in the TNBS-induced colitis model, whereas others had weaker or no preventive effect at all, as evidenced by colitis markers (body-weight loss, macroscopic and histological scores, myeloperoxidase activities and blood inflammatory markers). A careful selection of strains is required among the biodiversity of yeasts for specific clinical studies, including applications in inflammatory bowel disease and other therapeutic uses.

  16. MFSD2A Promotes Endothelial Generation of Inflammation-Resolving Lipid Mediators and Reduces Colitis in Mice.

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    Ungaro, Federica; Tacconi, Carlotta; Massimino, Luca; Corsetto, Paola Antonia; Correale, Carmen; Fonteyne, Philippe; Piontini, Andrea; Garzarelli, Valeria; Calcaterra, Francesca; Della Bella, Silvia; Spinelli, Antonino; Carvello, Michele; Rizzo, Angela Maria; Vetrano, Stefania; Petti, Luciana; Fiorino, Gionata; Furfaro, Federica; Mavilio, Domenico; Maddipati, Krishna Rao; Malesci, Alberto; Peyrin-Biroulet, Laurent; D'Alessio, Silvia; Danese, Silvio

    2017-11-01

    Alterations in signaling pathways that regulate resolution of inflammation (resolving pathways) contribute to pathogenesis of ulcerative colitis (UC). The resolution process is regulated by lipid mediators, such as those derived from the ω-3 docosahexaenoic acid (DHA), whose esterified form is transported by the major facilitator superfamily domain containing 2A (MFSD2A) through the endothelium of brain, retina, and placenta. We investigated if and how MFSD2A regulates lipid metabolism of gut endothelial cells to promote resolution of intestinal inflammation. We performed lipidomic and functional analyses of MFSD2A in mucosal biopsies and primary human intestinal microvascular endothelial cells (HIMECs) isolated from surgical specimens from patients with active, resolving UC and healthy individuals without UC (controls). MFSD2A was knocked down in HIMECs with small hairpin RNAs or overexpressed from a lentiviral vector. Human circulating endothelial progenitor cells that overexpress MFSD2A were transferred to CD1 nude mice with dextran sodium sulfate-induced colitis, with or without oral administration of DHA. Colonic biopsies from patients with UC had reduced levels of inflammation-resolving DHA-derived epoxy metabolites compared to healthy colon tissues or tissues with resolution of inflammation. Production of these metabolites by HIMECs required MFSD2A, which is required for DHA retention and metabolism in the gut vasculature. In mice with colitis, transplanted endothelial progenitor cells that overexpressed MFSD2A not only localized to the inflamed mucosa but also restored the ability of the endothelium to resolve intestinal inflammation, compared with mice with colitis that did not receive MFSD2A-overexpressing endothelial progenitors. Levels of DHA-derived epoxides are lower in colon tissues from patients with UC than healthy and resolving mucosa. Production of these metabolites by gut endothelium requires MFSD2A; endothelial progenitor cells that

  17. Intestinal anti-inflammatory activity of the seeds of Raphanus sativus L. in experimental ulcerative colitis models.

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    Choi, Ki-Choon; Cho, Seong-Wan; Kook, Sung-Ho; Chun, Sa-Ra; Bhattarai, Govinda; Poudel, Sher Bahadur; Kim, Min-Kook; Lee, Kyung-Yeol; Lee, Jeong-Chae

    2016-02-17

    Water extract of Raphanus sativus L. (RSL) seeds was traditionally used to treat digestive inflammatory complaints in Korean culture. RSL seeds exerted antioxidant, anti-inflammatory, and anti-septic functions, suggesting their pharmacological potential for the treatment of inflammatory pathologies associated with oxidative stress such as inflammatory bowel disease. We evaluated the intestinal anti-inflammatory effects of RSL seed water extract (RWE) in experimental rat models of trinitrobenzenesulphonic acid (TNBS)- or dextran sodium sulfate (DSS)-induced colitis. RWE was characterized by determining the content of sinapic acid as a reference material and then assayed in the DSS and TNBS models of rat colitis. Male Sprague-Dawley rats were divided into 10 groups (n=7/group): non-colitic control, DSS or TNBS control, DSS colitis groups treated with RWE (100mg/kg) or mesalazine (25mg/kg), and TNBS colitis groups treated with various doses (10, 40, 70, and 100mg/kg) of RWE or mesalazine (25mg/kg). RWE or mesalazine treatment started the same day of colitis induction and rats were sacrificed 24h after the last treatment followed by histological and biochemical analyses. Oral administration with RWE suppressed intestinal inflammatory damages in both DSS- and TNBS-induced colitic rats. The treatment with 100mg/kg RWE recovered intestinal damages caused by TNBS or DSS to levels similar to that of mesalazine, decreasing the activity of myeloperoxidase activity and the secretion of tumor necrosis factor (TNF)-α and interleukin (IL)-1β. RWE treatment inhibited malondialdehyde production and glutathione reduction in colon of colitis rats. The administration of RWE at dose of 100mg/kg also suppressed the TNBS- or DSS-stimulated expression of TNF-α, IL-1β, monocyte chemotactic protein-1, inducible nitric oxide, and intercellular adhesion molecule-1. Furthermore, RWE inhibited p38 kinase and DNA-nuclear factor-κB binding activities, both of which were stimulated in the

  18. Anti-inflammatory effect of Chang-An-Shuan on TNBS-induced experimental colitis in rats.

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    Mi, Hong; Liu, Feng-Bin; Li, Hai-Wen; Hou, Jiang-Tao; Li, Pei-Wu

    2017-06-15

    Inflammatory bowel disease (IBD), denominated by Crohn's disease and ulcerative colitis, is often associated with abdominal pain, diarrhea and bloody stool. The standard protocols for treating colitis conditions are not satisfactory; thus, complementary and alternative medicines have been increasingly accepted by IBD sufferers worldwide. In this study, we aimed to elucidate the anti-inflammatory effect of Chang-An-Shuan (CAS), a 6-herb Chinese medicinal formula, on 2, 4, 6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats and the underlying mechanisms. Sprague-Dawley rats were administered with rectal gavage of 2.5% TNBS in 50% ethanol for the induction of experimental colitis which is considered as a model for Crohn's disease. Upon the TNBS induction, rats were given CAS at 0.5 g/kg/day or 5 g/kg/day for 10 days. The application of salicylazosulfapyridine (0.5 g/kg/day) was served as a positive reference drug for the colitis condition. The efficacy and mechanistic action of CAS were evaluated by means of histopathological and biochemical approaches such as histological staining, real-time polymerase chain reaction, Western blotting analysis and enzyme-linked immunosorbent assay. Oral administration of CAS at 5 g/kg/day, but not 0.5 g/kg/day, significantly ameliorated the severity of TNBS-induced colitis as evidenced by the reduced loss of body weight, alleviated diarrhea and decreased bloody stool. While lowering the disease activity index, the administration of CAS lessened mucosal lesions thus mucosal integrity of the colitis rats was notably improved. Further, the CAS treatment also significantly suppressed the mRNA and protein levels of pro-inflammatory cytokines, namely interleukin-1β and tumor necrosis factor-α while enhancing the level of anti-inflammatory cytokine IL-10 in the TNBS-treated rats. Importantly, the ameliorative effect of CAS was related to an inhibition of the nuclear factor-κB (NF-κB) signaling pathway by downregulating

  19. Anti-melanin-concentrating hormone treatment attenuates chronic experimental colitis and fibrosis.

    Science.gov (United States)

    Ziogas, Dimitrios C; Gras-Miralles, Beatriz; Mustafa, Sarah; Geiger, Brenda M; Najarian, Robert M; Nagel, Jutta M; Flier, Sarah N; Popov, Yury; Tseng, Yu-Hua; Kokkotou, Efi

    2013-05-15

    Fibrosis represents a major complication of several chronic diseases, including inflammatory bowel disease (IBD). Treatment of IBD remains a clinical challenge despite several recent therapeutic advances. Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide shown to regulate appetite and energy balance. However, accumulating evidence suggests that MCH has additional biological effects, including modulation of inflammation. In the present study, we examined the efficacy of an MCH-blocking antibody in treating established, dextran sodium sulfate-induced experimental colitis. Histological and molecular analysis of mouse tissues revealed that mice receiving anti-MCH had accelerated mucosal restitution and lower colonic expression of several proinflammatory cytokines, as well as fibrogenic genes, including COL1A1. In parallel, they spared collagen deposits seen in the untreated mice, suggesting attenuated fibrosis. These findings raised the possibility of perhaps direct effects of MCH on myofibroblasts. Indeed, in biopsies from patients with IBD, we demonstrate expression of the MCH receptor MCHR1 in α-smooth muscle actin(+) subepithelial cells. CCD-18Co cells, a primary human colonic myofibroblast cell line, were also positive for MCHR1. In these cells, MCH acted as a profibrotic modulator by potentiating the effects of IGF-1 and TGF-β on proliferation and collagen production. Thus, by virtue of combined anti-inflammatory and anti-fibrotic effects, blocking MCH might represent a compelling approach for treating IBD.

  20. Fumigaclavine C ameliorates dextran sulfate sodium-induced murine experimental colitis via NLRP3 inflammasome inhibition

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    Wenjie Guo

    2015-10-01

    Full Text Available In the present study, the effect of Fumigaclavine C, a fungal metabolite, on murine experimental colitis induced by dextran sulfate sodium (DSS and its possible mechanism were examined in vivo and vitro. Oral administration of Fumigaclavine C dose-dependently attenuated the loss of body weight and shortening of colon length induced by DSS. The disease activity index, histopathologic scores of musco was also significantly reduced by Fumigaclavine C treatment. Protein and mRNA levels of DSS-induced pro-inflammatory cytokines in colon, including TNF-α, IL-1β and IL-17A, were markedly suppressed by Fumigaclavine C. At the same time, decreased activation of caspase-1 in peritoneal macrophages was detected in Fumigaclavine C -treated mice which suggested that the NLRP3 inflammasome activation was suppressed. Furthermore, in the LPS plus ATP cell model, we found that Fumigaclavine C dose-dependent inhibited IL-1β release and caspase-1 activation. Taken together, our results demonstrate the ability of Fumigaclavine C to inhibit NLRP3 inflammasome activation and give some evidence for its potential use in the treatment of inflammatory bowel diseases.

  1. Contrasting immune responses mediate Campylobacter jejuni-induced colitis and autoimmunity.

    Science.gov (United States)

    Malik, A; Sharma, D; St Charles, J; Dybas, L A; Mansfield, L S

    2014-07-01

    Campylobacter jejuni is a leading cause of foodborne enteritis that has been linked to the autoimmune neuropathy, Guillain Barré syndrome (GBS). C57BL/6 interleukin (IL)-10(+/+) and congenic IL-10(-/-) mice serve as C. jejuni colonization and colitis models, respectively, but a mouse model for GBS is lacking. We demonstrate that IL-10(-/-) mice infected with a C. jejuni colitogenic human isolate had significantly upregulated type 1 and 17 but not type 2 cytokines in the colon coincident with infiltration of phagocytes, T cells and innate lymphoid cells (ILCs). Both ILC and T cells participated in interferon-γ (IFN-γ), IL-17, and IL-22 upregulation but in a time- and organ-specific manner. T cells were, however, necessary for colitis as mice depleted of Thy-1(+) cells were protected while neither Rag1(-/-) nor IL-10R blocked Rag1(-/-) mice developed colitis after infection. Depleting IFN-γ, IL-17, or both significantly ameliorated colitis and drove colonic responses toward type 2 cytokine and antibody induction. In contrast, C. jejuni GBS patient strains induced mild colitis associated with blunted type 1/17 but enhanced type 2 responses. Moreover, the type 2 but not type 1/17 antibodies cross-reacted with peripheral nerve gangliosides demonstrating autoimmunity.

  2. Electroacupuntura en el tratamiento de la colitis ulcerosa experimental en ratas Sprague Dawley - Electro acupuncture in the treatment of experimental ulcerous colitis in Sprague Dawley rats

    OpenAIRE

    Molina Martínez, José L.; Cuesta Mazorra, Mario; Silveira Prado, Enrique A; Castro Gutiérrez, Maribel; González Madariaga, Yisell; Sánchez Álvarez, Carmen; Blanco Machado, Freisman; Verdecia Machado, Belkis; Rodriguez Santos, Caridad

    2010-01-01

    ResumenSe realizó un estudio sobre la efectividad terapéutica de la electroacupuntura (EA) en la colitis ulcerosa (CU) provocada experimentalmente en ratas Sprague Dawley por administración intracolónica de una disolución de ácido acético al 4%. El experimento se realizó en 57 ratas distribuidas en tres grupos: Grupo I (control placebo), al que se administró solución salina fisiológica mediante instilación intracolónica, Grupo II (control no tratado) y Grupo III (estudio), integrado ambos por...

  3. Intestinal Epithelial Serum Amyloid A Modulates Bacterial Growth In Vitro and Pro-Inflammatory Responses in Mouse Experimental Colitis

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    Wang Yu

    2010-11-01

    Full Text Available Abstract Background Serum Amyloid A (SAA is a major acute phase protein of unknown function. SAA is mostly expressed in the liver, but also in other tissues including the intestinal epithelium. SAA reportedly has anti-bacterial effects, and because inflammatory bowel diseases (IBD result from a breakdown in homeostatic interactions between intestinal epithelia and bacteria, we hypothesized that SAA is protective during experimental colitis. Methods Intestinal SAA expression was measured in mouse and human samples. Dextran sodium sulfate (DSS colitis was induced in SAA 1/2 double knockout (DKO mice and in wildtype controls. Anti-bacterial effects of SAA1/2 were tested in intestinal epithelial cell lines transduced with adenoviral vectors encoding the CE/J SAA isoform or control vectors prior to exposure to live Escherichia coli. Results Significant levels of SAA1/SAA2 RNA and SAA protein were detected by in situ hybridization and immunohistochemistry in mouse colonic epithelium. SAA3 expression was weaker, but similarly distributed. SAA1/2 RNA was present in the ileum and colon of conventional mice and in the colon of germfree mice. Expression of SAA3 was strongly regulated by bacterial lipopolysaccharides in cultured epithelial cell lines, whereas SAA1/2 expression was constitutive and not LPS inducible. Overexpression of SAA1/2 in cultured epithelial cell lines reduced the viability of co-cultured E. coli. This might partially explain the observed increase in susceptibility of DKO mice to DSS colitis. SAA1/2 expression was increased in colon samples obtained from Crohn's Disease patients compared to controls. Conclusions Intestinal epithelial SAA displays bactericidal properties in vitro and could play a protective role in experimental mouse colitis. Altered expression of SAA in intestinal biopsies from Crohn's Disease patients suggests that SAA is involved in the disease process..

  4. Resident Bacteria-Stimulated Interleukin-10-Secreting B Cells Ameliorate T-Cell-Mediated Colitis by Inducing T-Regulatory-1 Cells That Require Interleukin-27 SignalingSummary

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    Yoshiyuki Mishima

    2015-05-01

    Full Text Available Background & Aims: The regulatory roles of interleukin-10 (IL10-producing B cells in colitis are not fully understood, so we explored the molecular mechanisms by which these cells modulate mucosal homeostasis. Methods: CD4+ T cells from wild-type (WT, Il10−/−, or Il27ra−/− mice were cotransferred with B cells from specific pathogen-free (SPF or germ-free (GF WT or Il10−/− mice into Rag2−/−Il10−/−(double-knockout mice, and the severity of colitis and intestinal regulatory T-cell populations were characterized. In vitro, WT or Il10−/− B cells were cocultured with unfractionated, naïve or regulatory T cells plus Il10−/− antigen-presenting cells and stimulated with cecal bacterial lysate (CBL with or without IL27 or anti-IL10R blockade. Gene expressions, cytokines in the supernatant and cell populations were assessed. Results: WT but not Il10−/− B cells attenuated T helper cell TH1/TH17-mediated colitis in double-knockout mice that also received WT but not Il10−/− T cells. In vitro, CBL-stimulated WT B cells secrete abundant IL10 and suppress interferon-γ (IFNγ and IL17a-production by T cells without requiring cell contact. Although both WT and Il10−/− B cells induced Foxp3+CD4+ T-regulatory cells, only WT B cells induced IL10-producing (Foxp3-negative T regulatory-1 (Tr-1 cells both in vivo and in vitro. However, IL10-producing B cells did not attenuate colitis or induce Tr-1 cells in the absence of T cell IL27 signaling in vivo. WT B cell-dependent Tr-1 induction and concomitant decreased IFNγ-secretion were also mediated by T-cell IL27-signaling in vitro. Conclusions: IL10-secreting B cells activated by physiologically relevant bacteria ameliorate T-cell-mediated colitis and contribute to intestinal homeostasis by suppressing effector T cells and inducing Tr-1 cells via IL27-signaling on T cells. Keywords: Experimental

  5. 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

  6. Use of Propolis Hydroalcoholic Extract to Treat Colitis Experimentally Induced in Rats by 2,4,6-Trinitrobenzenesulfonic Acid

    Directory of Open Access Journals (Sweden)

    Cely Cristina Martins Gonçalves

    2013-01-01

    Full Text Available This study focused on the therapeutic effect of a propolis SLNC 106PI extract on experimental colitis. Wistar adult rats received 0.8 mL rectal dose of one of the following solutions: saline (group S, 20 mg TNBS in 50% ethanol (group TNBS, 20 mg TNBS in 50% ethanol and propolis extract in saline (group TNBS-P, propolis extract in saline (group SP, and 20 mg TNBS in 50% ethanol and 50 mg/kg mesalazine (group TNBS-M. The animals were euthanized 7 or 14 days after the colitis induction. Samples of the distal colon were harvested for the analysis of myeloperoxidase (MPO enzyme activity and for morphometric analysis in paraffin-embedded histological sections with hematoxylin-eosin or histochemical staining. The animals treated with TNBS exhibited the typical clinical signs of colitis. Increased MPO activity confirmed the presence of inflammation. TNBS induced the development of megacolon, ulceration, transmural inflammatory infiltrate, and thickened bowel walls. Treatment with propolis moderately reduced the inflammatory response, decreased the number of cysts and abscesses, inhibited epithelial proliferation, and increased the number of goblet cells. The anti-inflammatory activity of the propolis SLNC 106 extract was confirmed by the reductions in both the inflammatory infiltrate and the number of cysts and abscesses in the colon mucosa.

  7. Synthesis and evaluation of anti-inflammatory properties of silver nanoparticle suspensions in experimental colitis in mice.

    Science.gov (United States)

    Siczek, Krzysztof; Zatorski, Hubert; Chmielowiec-Korzeniowska, Anna; Pulit-Prociak, Jolanta; Śmiech, Magdalena; Kordek, Radzisław; Tymczyna, Leszek; Banach, Marcin; Fichna, Jakub

    2017-04-01

    The aim of our study was to investigate the effect of newly developed silver nanoparticle aqueous suspensions NanoAg1 and NanoAg2 in the mouse models mimicking ulcerative colitis and Crohn's disease. NanoAg1 and NanoAg2 were synthesized in aqueous medium with the involvement of tannic acid. To elucidate their anti-inflammatory activity, semi-chronic mouse models of inflammation induced by dextrane sulfate sodium addition to drinking water and intracolonic (i.c.) administration of 2,4,6-trinitrobenzenesulfonic acid were used. NanoAg1 and NanoAg2 (500 mg/dm3, 100 μl/animal, i.c., once daily) significantly ameliorated colitis in dextrane sulfate sodium- and 2,4,6-trinitrobenzenesulfonic acid-induced mouse models of colonic inflammation, as indicated by reduced macroscopic, ulcer and microscopic scores. The anti-inflammatory effect was dependent on the shape and diameter of silver nanoparticles, as indicated by weaker effect of NanoAg1 than NanoAg2. In addition, administration of NanoAg2, but not NanoAg1, modulated colonic microbiota, as indicated by reduced number of Escherichia coli and Clostridium perfringens, and increased number of Lactobacillus sp. Summarizing, NanoAg1 and NanoAg2 after administered i.c. effectively alleviate colitis in experimental models of ulcerative colitis and Crohn's disease in mice. Therefore, NanoAg1 and NanoAg2 administered i.c. have the potential to become valuable agents for the treatment of inflammatory bowel diseases. © 2016 John Wiley & Sons A/S.

  8. The TRPA1 ion channel is expressed in CD4+ T cells and restrains T-cell-mediated colitis through inhibition of TRPV1.

    Science.gov (United States)

    Bertin, Samuel; Aoki-Nonaka, Yukari; Lee, Jihyung; de Jong, Petrus R; Kim, Peter; Han, Tiffany; Yu, Timothy; To, Keith; Takahashi, Naoki; Boland, Brigid S; Chang, John T; Ho, Samuel B; Herdman, Scott; Corr, Maripat; Franco, Alessandra; Sharma, Sonia; Dong, Hui; Akopian, Armen N; Raz, Eyal

    2017-09-01

    Transient receptor potential ankyrin-1 (TRPA1) and transient receptor potential vanilloid-1 (TRPV1) are calcium (Ca2+)-permeable ion channels mostly known as pain receptors in sensory neurons. However, growing evidence suggests their crucial involvement in the pathogenesis of IBD. We explored the possible contribution of TRPA1 and TRPV1 to T-cell-mediated colitis. We evaluated the role of Trpa1 gene deletion in two models of experimental colitis (ie, interleukin-10 knockout and T-cell-adoptive transfer models). We performed electrophysiological and Ca2+ imaging studies to analyse TRPA1 and TRPV1 functions in CD4+ T cells. We used genetic and pharmacological approaches to evaluate TRPV1 contribution to the phenotype of Trpa1-/- CD4+ T cells. We also analysed TRPA1 and TRPV1 gene expression and TRPA1+TRPV1+ T cell infiltration in colonic biopsies from patients with IBD. We identified a protective role for TRPA1 in T-cell-mediated colitis. We demonstrated the functional expression of TRPA1 on the plasma membrane of CD4+ T cells and identified that Trpa1-/- CD4+ T cells have increased T-cell receptor-induced Ca2+ influx, activation profile and differentiation into Th1-effector cells. This phenotype was abrogated upon genetic deletion or pharmacological inhibition of the TRPV1 channel in mouse and human CD4+ T cells. Finally, we found differential regulation of TRPA1 and TRPV1 gene expression as well as increased infiltration of TRPA1+TRPV1+ T cells in the colon of patients with IBD. Our study indicates that TRPA1 inhibits TRPV1 channel activity in CD4+ T cells, and consequently restrains CD4+ T-cell activation and colitogenic responses. These findings may therefore have therapeutic implications for human IBD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  9. Anti-Inflammatory Action of Angiotensin 1-7 in Experimental Colitis

    Science.gov (United States)

    Khajah, Maitham A.; Fateel, Maryam M.; Ananthalakshmi, Kethireddy V.; Luqmani, Yunus A.

    2016-01-01

    Background There is evidence to support a role for angiotensin (Ang) 1–7 in reducing the activity of inflammatory signaling molecules such as MAPK, PKC and SRC. Enhanced angiotensin converting enzyme 2 (ACE2) expression has been observed in patients with inflammatory bowel disease (IBD) suggesting a role in its pathogenesis, prompting this study. Methods The colonic expression/activity profile of ACE2, Ang 1–7, MAS1-receptor (MAS1-R), MAPK family and Akt were determined by western blot and immunofluorescence. The effect of either exogenous administration of Ang 1–7 or pharmacological inhibition of its function (by A779 treatment) was determined using the mouse dextran sulfate sodium model. Results Enhanced colonic expression of ACE2, Ang1-7 and MAS1-R was observed post-colitis induction. Daily Ang 1–7 treatment (0.01–0.06 mg/kg) resulted in significant amelioration of DSS-induced colitis. In contrast, daily administration of A779 significantly worsened features of colitis. Colitis-associated phosphorylation of p38, ERK1/2 and Akt was reduced by Ang 1–7 treatment. Conclusion Our results indicate important anti-inflammatory actions of Ang 1–7 in the pathogenesis of IBD, which may provide a future therapeutic strategy to control the disease progression. PMID:26963721

  10. 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.

    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

  11. Relative contributions of NOS isoforms during experimental colitis: endothelial-derived NOS maintains mucosal integrity

    NARCIS (Netherlands)

    Vallance, Bruce A.; Dijkstra, Gerard; Qiu, Bosheng; van der Waaij, Laurens A.; van Goor, Harry; Jansen, Peter L. M.; Mashimo, Hiroshi; Collins, Stephen M.

    2004-01-01

    The role of nitric oxide (NO) in inflammatory bowel diseases has traditionally focused on the inducible form of NO synthase (iNOS). However, the constitutive endothelial (eNOS) and neuronal (nNOS) isoforms may also impact on colitis, either by contributing to the inflammation or by regulating

  12. Allogeneic guinea pig mesenchymal stem cells ameliorate neurological changes in experimental colitis.

    Science.gov (United States)

    Stavely, Rhian; Robinson, Ainsley M; Miller, Sarah; Boyd, Richard; Sakkal, Samy; Nurgali, Kulmira

    2015-12-30

    The use of mesenchymal stem cells (MSCs) to treat inflammatory bowel disease (IBD) is of great interest because of their immunomodulatory properties. Damage to the enteric nervous system (ENS) is implicated in IBD pathophysiology and disease progression. The most commonly used model to study inflammation-induced changes to the ENS is 2,4,6-trinitrobenzene-sulfonate acid (TNBS)-induced colitis in guinea pigs; however, no studies using guinea pig MSCs in colitis have been performed. This study aims to isolate and characterise guinea pig MSCs and then test their therapeutic potential for the treatment of enteric neuropathy associated with intestinal inflammation. MSCs from guinea pig bone marrow and adipose tissue were isolated and characterised in vitro. In in vivo experiments, guinea pigs received either TNBS for the induction of colitis or sham treatment by enema. MSCs were administered at a dose of 1 × 10(6) cells via enema 3 h after the induction of colitis. Colon tissues were collected 24 and 72 h after TNBS administration to assess the level of inflammation and damage to the ENS. The secretion of transforming growth factor-β1 (TGF-β1) was analysed in MSC conditioned medium by flow cytometry. Cells isolated from both sources were adherent to plastic, multipotent and expressed some human MSC surface markers. In vitro characterisation revealed distinct differences in growth kinetics, clonogenicity and cell morphology between MSC types. In an in vivo model of TNBS-induced colitis, guinea pig bone marrow MSCs were comparatively more efficacious than adipose tissue MSCs in attenuating weight loss, colonic tissue damage and leukocyte infiltration into the mucosa and myenteric plexus. MSCs from both sources were equally neuroprotective in the amelioration of enteric neuronal loss and changes to the neurochemical coding of neuronal subpopulations. MSCs from both sources secreted TGF-β1 which exerted neuroprotective effects in vitro. This study is the first

  13. Localized delivery of interferon-β by Lactobacillus exacerbates experimental colitis.

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    Adelle P McFarland

    2011-02-01

    Full Text Available There have been conflicting reports of the role of Type I interferons (IFN in inflammatory bowel disease (IBD. Clinical trials have shown potent efficacy of systemic interferon-beta (IFN-β in inducing remission of ulcerative colitis. Likewise, IFNAR1(-/- mice display an increased sensitivity to dextran sulfate sodium (DSS-induced colitis, suggesting Type I IFN play a protective role during inflammation of the gut. Curiously, however, there have also been reports detailing the spontaneous development of IBD in patients receiving systemic IFN-β therapy for multiple sclerosis or hepatitis.To investigate the effects of local administration of IFN-β on a murine model of colitis, we developed a transgenic Lactobacillus acidophilus strain that constitutively expresses IFN-β (La-IFN-β. While pretreatment of mice with control Lactobacillus (La-EV provided slight protective benefits, La-IFN-β increased sensitivity to DSS. Analysis showed colitic mice pretreated with La-IFN-β had increased production of TNF-α, IFN-γ, IL-17A and IL-13 by intestinal tissues and decreased regulatory T cells (Tregs in their small intestine. Examination of CD103(+ dendritic cells (DCs in the Peyer's patches revealed that IFNAR1 expression was dramatically reduced by La-IFN-β. Similarly, bone marrow-derived DCs matured with La-IFN-β experienced a 3-fold reduction of IFNAR1 and were impaired in their ability to induce Tregs.Our IFNAR1 expression data identifies a correlation between the loss/downregulation of IFNAR1 on DCs and exacerbation of colitis. Our data show that Lactobacillus secreting IFN-β has an immunological effect that in our model results in the exacerbation of colitis. This study underscores that the selection of therapeutics delivered by a bacterial vehicle must take into consideration the simultaneous effects of the vehicle itself.

  14. 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.

  15. Microbiome-mediated neutrophil recruitment via CXCR2 and protection from amebic colitis.

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    Koji Watanabe

    2017-08-01

    Full Text Available The disease severity of Entamoeba histolytica infection ranges from asymptomatic to life-threatening. Recent human and animal data implicate the gut microbiome as a modifier of E. histolytica virulence. Here we have explored the association of the microbiome with susceptibility to amebiasis in infants and in the mouse model of amebic colitis. Dysbiosis occurred symptomatic E. histolytica infection in children, as evidenced by a lower Shannon diversity index of the gut microbiota. To test if dysbiosis was a cause of susceptibility, wild type C57BL/6 mice (which are innately resistant to E. histiolytica infection were treated with antibiotics prior to cecal challenge with E. histolytica. Compared with untreated mice, antibiotic pre-treated mice had more severe colitis and delayed clearance of E. histolytica. Gut IL-25 and mucus protein Muc2, both shown to provide innate immunity in the mouse model of amebic colitis, were lower in antibiotic pre-treated mice. Moreover, dysbiotic mice had fewer cecal neutrophils and myeloperoxidase activity. Paradoxically, the neutrophil chemoattractant chemokines CXCL1 and CXCL2, as well as IL-1β, were higher in the colon of mice with antibiotic-induced dysbiosis. Neutrophils from antibiotic pre-treated mice had diminished surface expression of the chemokine receptor CXCR2, potentially explaining their inability to migrate to the site of infection. Blockade of CXCR2 increased susceptibility of control non-antibiotic treated mice to amebiasis. In conclusion, dysbiosis increased the severity of amebic colitis due to decreased neutrophil recruitment to the gut, which was due in part to decreased surface expression on neutrophils of CXCR2.

  16. Microbiome-mediated neutrophil recruitment via CXCR2 and protection from amebic colitis

    Science.gov (United States)

    Watanabe, Koji; Uddin, Md Jashim; Burgess, Stacey L.; Abhyankar, Mayuresh M.; Moonah, Shannon N.; Noor, Zannatun; Donowitz, Jeffrey R.; Schneider, Brittany N.; Kabir, Mamun; Haque, Rashidul

    2017-01-01

    The disease severity of Entamoeba histolytica infection ranges from asymptomatic to life-threatening. Recent human and animal data implicate the gut microbiome as a modifier of E. histolytica virulence. Here we have explored the association of the microbiome with susceptibility to amebiasis in infants and in the mouse model of amebic colitis. Dysbiosis occurred symptomatic E. histolytica infection in children, as evidenced by a lower Shannon diversity index of the gut microbiota. To test if dysbiosis was a cause of susceptibility, wild type C57BL/6 mice (which are innately resistant to E. histiolytica infection) were treated with antibiotics prior to cecal challenge with E. histolytica. Compared with untreated mice, antibiotic pre-treated mice had more severe colitis and delayed clearance of E. histolytica. Gut IL-25 and mucus protein Muc2, both shown to provide innate immunity in the mouse model of amebic colitis, were lower in antibiotic pre-treated mice. Moreover, dysbiotic mice had fewer cecal neutrophils and myeloperoxidase activity. Paradoxically, the neutrophil chemoattractant chemokines CXCL1 and CXCL2, as well as IL-1β, were higher in the colon of mice with antibiotic-induced dysbiosis. Neutrophils from antibiotic pre-treated mice had diminished surface expression of the chemokine receptor CXCR2, potentially explaining their inability to migrate to the site of infection. Blockade of CXCR2 increased susceptibility of control non-antibiotic treated mice to amebiasis. In conclusion, dysbiosis increased the severity of amebic colitis due to decreased neutrophil recruitment to the gut, which was due in part to decreased surface expression on neutrophils of CXCR2. PMID:28817707

  17. Impact of probiotics on toll-like receptor 4 expression in an experimental model of ulcerative colitis.

    Science.gov (United States)

    Yang, Xia; Fu, Yu; Liu, Jun; Ren, Hong-yu

    2013-10-01

    Toll-like receptors (TLRs) are key components of the innate immune system which trigger antimicrobial host defense responses. This study aimed to investigate the impact of probiotics (Lactobacillus, Bifidobacterium) on the expression of TLR4 and tumor necrosis factor-alpha (TNF-α) in the colon mucosa of rat experimental ulcerative colitis model induced by trinitrobenzene sulfonic acid (TNBS)/ethanol and immune complexes. The gross and histological changes of the colonic mucosa were observed and assessed by the means-standard deviation and independent samples t-test. The protein expression levels of TLR4 and TNF-α were detected by using immunohistochemistry and Western blotting, respectively. It was revealed that there was visible infiltration of inflammatory cells, formation of crypt abscess, and the reduction of goblet cells in the colon tissue of experimental models. As compared with the control group, the levels of TLR4 and TNF-α protein were significantly increased in the model group (Pprobiotics treatment group and the model group (P>0.05), whereas significant reductions were shown in rats which were treated with probiotics for four weeks as compared with the model group (Pprobiotics-treated groups. Our results implied that probiotics were likely to play a key role in protecting ulcerative colitis by reducing the inflammatory factor TNF-α expression through inhibiting the TLR4 expression in the colon tissue of experimental models.

  18. Autoimmune regulator (AIRE)-deficient CD8+CD28low regulatory T lymphocytes fail to control experimental colitis.

    Science.gov (United States)

    Pomié, Céline; Vicente, Rita; Vuddamalay, Yirajen; Lundgren, Brita Ardesjö; van der Hoek, Mark; Enault, Geneviève; Kagan, Jérémy; Fazilleau, Nicolas; Scott, Hamish S; Romagnoli, Paola; van Meerwijk, Joost P M

    2011-07-26

    Mutations in the gene encoding the transcription factor autoimmune regulator (AIRE) are responsible for autoimmune polyendocrinopathy candidiasis ectodermal dystrophy syndrome. AIRE directs expression of tissue-restricted antigens in the thymic medulla and in lymph node stromal cells and thereby substantially contributes to induction of immunological tolerance to self-antigens. Data from experimental mouse models showed that AIRE deficiency leads to impaired deletion of autospecific T-cell precursors. However, a potential role for AIRE in the function of regulatory T-cell populations, which are known to play a central role in prevention of immunopathology, has remained elusive. Regulatory T cells of CD8(+)CD28(low) phenotype efficiently control immune responses in experimental autoimmune and colitis models in mice. Here we show that CD8(+)CD28(low) regulatory T lymphocytes from AIRE-deficient mice are transcriptionally and phenotypically normal and exert efficient suppression of in vitro immune responses, but completely fail to prevent experimental colitis in vivo. Our data therefore demonstrate that AIRE plays an important role in the in vivo function of a naturally occurring regulatory T-cell population.

  19. TLR2 and interleukin-10 are involved in Bacteroides fragilis-mediated prevention of DSS-induced colitis in gnotobiotic mice.

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    Yi-Chih Chang

    Full Text Available Bacteroides fragilis (BF are Gram-negative anaerobe symbionts present in the colon. Recent studies have reported the beneficial role of BF in maintaining intestinal homeostasis, stimulating host immunologic development, and preventing infectious colitis caused by pathogenic bacteria. Our previous studies showed that monocolonization of germ-free mice with BF significantly reduced colon inflammations and damage.In order to investigate the Toll-like receptor-2 (TLR2, TLR4, and interleukin 10 (IL-10 molecular signaling pathways involved in BF-mediated prevention of dextran sulfate sodium (DSS-induced colitis. The wild-type (WT, TLR4, TLR2, and IL-10 knockout (-/- germ-free mice grown were with or without BF colonization for 28 days, and then administered 1% DSS in drinking water for 7 day to induce acute ulcerative colitis.We compared phenotypes such as weight loss, disease activity, intestinal histological scores, and immunohistochemistry for inflammatory cells. Unlike WT and TLR4-/- mice, the severity of DSS-colitis did not improve in TLR2-/- animals after BF colonization. The BF enhanced anti-inflammatory cytokines IL-10 expression and inhibited pro-inflammatory-related tumor necrosis factor (TNF-α and IL-6 mRNA expression in both WT and TLR4-/- mice. In contrast, the failed to up-regulated IL-10 and down-regulated the TNF-α and IL-6 in BF colonization TLR2-/- mice. In addition, we further perform IL-10-/- mice to clarify whether the BF through TLR2 /IL-10 pathway to alleviate DSS-colitis. There were no significant differences in colitis severity and pro-inflammatory related genes expression in the IL-10-/- mice with or without BF colonization.These results indicate the disease-preventing effects of BF in acute DSS-induced colitis may occur through the TLR2/IL-10 signal pathway.

  20. TLR2 and interleukin-10 are involved in Bacteroides fragilis-mediated prevention of DSS-induced colitis in gnotobiotic mice.

    Science.gov (United States)

    Chang, Yi-Chih; Ching, Yung-Hao; Chiu, Chien-Chao; Liu, Ju-Yun; Hung, Shao-Wen; Huang, Wen-Ching; Huang, Yen-Te; Chuang, Hsiao-Li

    2017-01-01

    Bacteroides fragilis (BF) are Gram-negative anaerobe symbionts present in the colon. Recent studies have reported the beneficial role of BF in maintaining intestinal homeostasis, stimulating host immunologic development, and preventing infectious colitis caused by pathogenic bacteria. Our previous studies showed that monocolonization of germ-free mice with BF significantly reduced colon inflammations and damage. In order to investigate the Toll-like receptor-2 (TLR2), TLR4, and interleukin 10 (IL-10) molecular signaling pathways involved in BF-mediated prevention of dextran sulfate sodium (DSS)-induced colitis. The wild-type (WT), TLR4, TLR2, and IL-10 knockout (-/-) germ-free mice grown were with or without BF colonization for 28 days, and then administered 1% DSS in drinking water for 7 day to induce acute ulcerative colitis. We compared phenotypes such as weight loss, disease activity, intestinal histological scores, and immunohistochemistry for inflammatory cells. Unlike WT and TLR4-/- mice, the severity of DSS-colitis did not improve in TLR2-/- animals after BF colonization. The BF enhanced anti-inflammatory cytokines IL-10 expression and inhibited pro-inflammatory-related tumor necrosis factor (TNF-α) and IL-6 mRNA expression in both WT and TLR4-/- mice. In contrast, the failed to up-regulated IL-10 and down-regulated the TNF-α and IL-6 in BF colonization TLR2-/- mice. In addition, we further perform IL-10-/- mice to clarify whether the BF through TLR2 /IL-10 pathway to alleviate DSS-colitis. There were no significant differences in colitis severity and pro-inflammatory related genes expression in the IL-10-/- mice with or without BF colonization. These results indicate the disease-preventing effects of BF in acute DSS-induced colitis may occur through the TLR2/IL-10 signal pathway.

  1. Aluminum enhances inflammation and decreases mucosal healing in experimental colitis in mice

    Science.gov (United States)

    Pineton de Chambrun, G; Body-Malapel, M; Frey-Wagner, I; Djouina, M; Deknuydt, F; Atrott, K; Esquerre, N; Altare, F; Neut, C; Arrieta, M C; Kanneganti, T-D; Rogler, G; Colombel, J-F; Cortot, A; Desreumaux, P; Vignal, C

    2014-01-01

    The increasing incidence of inflammatory bowel diseases (IBDs) in developing countries has highlighted the critical role of environmental pollutants as causative factors in their pathophysiology. Despite its ubiquity and immune toxicity, the impact of aluminum in the gut is not known. This study aimed to evaluate the effects of environmentally relevant intoxication with aluminum in murine models of colitis and to explore the underlying mechanisms. Oral administration of aluminum worsened intestinal inflammation in mice with 2,4,6-trinitrobenzene sulfonic acid- and dextran sodium sulfate-induced colitis and chronic colitis in interleukin 10-negative (IL10−/−) mice. Aluminum increased the intensity and duration of macroscopic and histologic inflammation, colonic myeloperoxidase activity, inflammatory cytokines expression, and decreased the epithelial cell renewal compared with control animals. Under basal conditions, aluminum impaired intestinal barrier function. In vitro, aluminum induced granuloma formation and synergized with lipopolysaccharide to stimulate inflammatory cytokines expression by epithelial cells. Deleterious effects of aluminum on intestinal inflammation and mucosal repair strongly suggest that aluminum might be an environmental IBD risk factor. PMID:24129165

  2. Aluminum enhances inflammation and decreases mucosal healing in experimental colitis in mice.

    Science.gov (United States)

    Pineton de Chambrun, G; Body-Malapel, M; Frey-Wagner, I; Djouina, M; Deknuydt, F; Atrott, K; Esquerre, N; Altare, F; Neut, C; Arrieta, M C; Kanneganti, T-D; Rogler, G; Colombel, J-F; Cortot, A; Desreumaux, P; Vignal, C

    2014-05-01

    The increasing incidence of inflammatory bowel diseases (IBDs) in developing countries has highlighted the critical role of environmental pollutants as causative factors in their pathophysiology. Despite its ubiquity and immune toxicity, the impact of aluminum in the gut is not known. This study aimed to evaluate the effects of environmentally relevant intoxication with aluminum in murine models of colitis and to explore the underlying mechanisms. Oral administration of aluminum worsened intestinal inflammation in mice with 2,4,6-trinitrobenzene sulfonic acid- and dextran sodium sulfate-induced colitis and chronic colitis in interleukin 10-negative (IL10(-/-)) mice. Aluminum increased the intensity and duration of macroscopic and histologic inflammation, colonic myeloperoxidase activity, inflammatory cytokines expression, and decreased the epithelial cell renewal compared with control animals. Under basal conditions, aluminum impaired intestinal barrier function. In vitro, aluminum induced granuloma formation and synergized with lipopolysaccharide to stimulate inflammatory cytokines expression by epithelial cells. Deleterious effects of aluminum on intestinal inflammation and mucosal repair strongly suggest that aluminum might be an environmental IBD risk factor.

  3. Azadirachta indica Attenuates Colonic Mucosal Damage in Experimental Colitis Induced by Trinitrobenzene Sulfonic Acid.

    Science.gov (United States)

    Gautam, M K; Goel, Shalini; Ghatule, R R; Singh, A; Joshi, V K; Goel, R K

    2013-09-01

    Azadirachta indica leaves indicated the presence of active principles with proven antioxidants, antiinflammatory, immunomodulatory, free radical scavenging and healing properties. In the present study we evaluated the healing effects of 50% ethanol extract of dried leaves of Azadirachta indica on trinitrobenzene sulfonic acid-induced colitis in rats. Azadirachta indica extract (500 mg/kg) was administered orally, once daily for 14 days and studied for its effects on diarrhoea, food and water intake, body weight changes, colonic damage and inflammation, histology, antibacterial activity and free radicals (nitric oxide and lipid peroxidation), antioxidants (superoxide dismutase, catalase and reduced glutathione) and myeloperoxidase activities in colonic tissue. Intracolonic trinitrobenzene sulfonic acid increased colonic mucosal damage and inflammation, diarrhea, but decreased body weight which were reversed by Azadirachta indica extract and sulfasalazine (positive control) treatments. Azadirachta indica extract showed antibacterial activity. Azadirachta indica extract and sulfasalazine enhanced the antioxidants but decreased free radicals and myeloperoxidase activities affected in trinitrobenzene sulfonic acid-induced colitis. Azadirachta indica extract, thus seemed to be effective in healing trinitrobenzene sulfonic acid-induced colitis in rats.

  4. A plant cell-expressed recombinant anti-TNF fusion protein is biologically active in the gut and alleviates immune-mediated hepatitis and colitis.

    Science.gov (United States)

    Ilan, Yaron; Gingis-Velitski, Svetlana; Ben Ya'aco, Ami; Shabbat, Yehudit; Zolotarov, Lidya; Almon, Einat; Shaaltiel, Yoseph

    2017-03-01

    The orally administered BY-2 plant cell-expressed recombinant anti-TNF fusion protein (PRX-106) (n=6) consists of the soluble form of the human TNF receptor (TNFR) fused to the Fc component of a human antibody IgG1 domain. To evaluate the immune modulatory effect of the oral administration of plant cells expressing PRX-106. Mice treated with Concanavalin A (ConA) to induce immune hepatitis was orally treated with cells expressing PRX-106 containing 0.5 or 5μg PRX 106. In the colitis model, TNBS-colitis was induced in mice followed by the oral administration of plant cells expressing PRX-106. The immune modulatory effect was determined through follow-up to assess the clinical effect, histology, and serum cytokine levels and by FACS analysis for lymphocyte subsets. The oral administration of BY-2 cells expressing PRX-106 alleviated immune-mediated liver injury. Serum AST and ALT levels decreased and were comparable to those of mice that had received high-dose steroids. The beneficial effect was also observed as a marked decrease in hepatic necrosis. In the colitis model, the oral administration of BY-2 plant cells expressing PRX-106 alleviated weight loss associated with immune-mediated colitis and improved bowel histology. A reduction in I-IkB-alpha phosphorylation in treated mice was also observed. These effects were associated with a significant alteration in the distribution of CD4+CD25+FOXP3+ cells. Plant cells expressing recombinant anti-TNF fusion protein show biological activity when orally administered, exerting an immune modulatory effect through the alleviation of immune-mediated hepatitis and immune-mediated colitis. Copyright © 2016 Elsevier GmbH. All rights reserved.

  5. Activation of neuronal P2X7 receptor-pannexin-1 mediates death of enteric neurons during colitis.

    Science.gov (United States)

    Gulbransen, Brian D; Bashashati, Mohammad; Hirota, Simon A; Gui, Xianyong; Roberts, Jane A; MacDonald, Justin A; Muruve, Daniel A; McKay, Derek M; Beck, Paul L; Mawe, Gary M; Thompson, Roger J; Sharkey, Keith A

    2012-03-18

    Inflammatory bowel diseases (IBDs) are chronic relapsing and remitting conditions associated with long-term gut dysfunction resulting from alterations to the enteric nervous system and a loss of enteric neurons. The mechanisms underlying inflammation-induced enteric neuron death are unknown. Here using in vivo models of experimental colitis we report that inflammation causes enteric neuron death by activating a neuronal signaling complex composed of P2X7 receptors (P2X7Rs), pannexin-1 (Panx1) channels, the Asc adaptor protein and caspases. Inhibition of P2X7R, Panx1, Asc or caspase activity prevented inflammation-induced neuron cell death. Preservation of enteric neurons by inhibiting Panx1 in vivo prevented the onset of inflammation-induced colonic motor dysfunction. Panx1 expression was reduced in Crohn's disease but not ulcerative colitis. We conclude that activation of neuronal Panx1 underlies neuron death and the subsequent development of abnormal gut motility in IBD. Targeting Panx1 represents a new neuroprotective strategy to ameliorate the progression of IBD-associated dysmotility.

  6. MAR binding protein SMAR1 favors IL-10 mediated regulatory T cell function in acute colitis

    Energy Technology Data Exchange (ETDEWEB)

    Mirlekar, Bhalchandra; Patil, Sachin [Chromatin and Disease Biology Laboratory, National Centre for Cell Science, Ganeshkhind, Pune 411007 (India); Bopanna, Ramanamurthy [Experimental Animal Facility, National Centre for Cell Science, Ganeshkhind, Pune 411007 (India); Chattopadhyay, Samit, E-mail: samit@nccs.res.in [Chromatin and Disease Biology Laboratory, National Centre for Cell Science, Ganeshkhind, Pune 411007 (India)

    2015-08-21

    T{sub reg} cells are not only crucial for controlling immune responses to autoantigens but also prevent those directed towards commensal pathogens. Control of effector immune responses by T{sub reg} cells depend on their capacity to accumulate at inflammatory site and accordingly accommodate to inflammatory environment. Till date, the factors associated with maintaining these aspects of T{sub reg} phenotype is not understood properly. Here we have shown that a known nuclear matrix binding protein SMAR1 is selectively expressed more in colonic T{sub reg} cells and is required for their ability to accumulate at inflammatory site and to sustain high levels of Foxp3 and IL-10 expression during acute colitis. Elimination of anti-inflammatory subsets revealed a protective role for IL-10 producing T{sub reg} cells in SMAR1{sup −/−} mice. Moreover, a combined action of Foxp3 and SMAR1 restricts effector cytokine production and enhance the production of IL-10 by colonic T{sub reg} cells that controls acute colitis. This data highlights a critical role of SMAR1 in maintaining T{sub reg} physiology during inflammatory disorders. - Highlights: • SMAR1 is essential to sustain high level of Foxp3 and IL-10 in T{sub reg} cells. • SMAR1{sup −/−} T{sub reg} cells produce pro-inflammatory cytokine IL-17 leads to inflammation. • IL-10 administration can control the inflammation in SMAR1{sup −/−} mice. • Both Foxp3 and SMAR1 maintain T{sub reg} phenotype that controls colitis.

  7. 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; Guo, Shuhong; Watterson, D. Martin; Ma, Thomas

    2015-01-01

    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. PMID:26514773

  8. The delay in the development of experimental colitis from isomaltosyloligosaccharides in rats is dependent on the degree of polymerization.

    Directory of Open Access Journals (Sweden)

    Hitoshi Iwaya

    Full Text Available Isomaltosyloligosaccharides (IMO and dextran (Dex are hardly digestible in the small intestine and thus influence the luminal environment and affect the maintenance of health. There is wide variation in the degree of polymerization (DP in Dex and IMO (short-sized IMO, S-IMO; long-sized IMO, L-IMO, and the physiological influence of these compounds may be dependent on their DP.Five-week-old male Wistar rats were given a semi-purified diet with or without 30 g/kg diet of the S-IMO (DP = 3.3, L-IMO (DP = 8.4, or Dex (DP = 1230 for two weeks. Dextran sulfate sodium (DSS was administered to the rats for one week to induce experimental colitis. We evaluated the clinical symptoms during the DSS treatment period by scoring the body weight loss, stool consistency, and rectal bleeding. The development of colitis induced by DSS was delayed in the rats fed S-IMO and Dex diets. The DSS treatment promoted an accumulation of neutrophils in the colonic mucosa in the rats fed the control, S-IMO, and L-IMO diets, as assessed by a measurement of myeloperoxidase (MPO activity. In contrast, no increase in MPO activity was observed in the Dex-diet-fed rats even with DSS treatment. Immune cell populations in peripheral blood were also modified by the DP of ingested saccharides. Dietary S-IMO increased the concentration of n-butyric acid in the cecal contents and the levels of glucagon-like peptide-2 in the colonic mucosa.Our study provided evidence that the physiological effects of α-glucosaccharides on colitis depend on their DP, linkage type, and digestibility.

  9. [Microscopic colitis].

    Science.gov (United States)

    Lukáš, Karel; Mandys, Václav

    2013-01-01

    Microscopic colitis is characterized by chronic or intermittent watery diarrhoea. Microscopic colitis is a common cause of chronic diarrhoea in predominantly older adults. The underlying mechanism in the pathogenesis of microscopic colitis remains unspecified. Microscopic colitis including colitis collagenous, lymphocytic, microscopic colitis with incomplete findings, minimal change colitis, eosinophilic colitis, Brainerd´s diarrhoea, graft-versus-host disease, mastocytic enterocolitis and postinfectious irritable bowel syndrome. Careful consideration of the clinical features and colonic mucosal biopsies usually lead to correct diagnosis. Treatments of microscopic colitis were based primarily on case reports and personal experience. Many medications have been proposed that either offer symptomatic relief (loperamide, cholestyramine) or had anti-inflammatory or immunosuppressive properties (aminosalicylates, steroids, adalimumab, azathioprine).

  10. 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.

  11. Beauvericin ameliorates experimental colitis by inhibiting activated T cells via downregulation of the PI3K/Akt signaling pathway.

    Directory of Open Access Journals (Sweden)

    Xue-Feng Wu

    Full Text Available Crohn's disease is a common, chronic inflammatory bowel condition characterized by remission and relapse. Accumulating evidence indicates that activated T cells play an important role in this disease. In the present study, we aimed to examine the effect of beauvericin, a natural cyclic peptide, on 2,4,6-trinitrobenzene sulfonic acid (TNBS-induced colitis in mice, which mimics Crohn's disease. Beauvericin significantly reduced weight loss, diarrhea and mortality, accompanied with notable alleviation of macroscopic and microscopic signs. In addition, this compound decreased serum levels of tumor necrosis factor (TNF-α and interferon (IFN-γ in a concentration-dependent manner in mice with experimental colitis. These effects of beauvericin are attributed to its inhibition on activated T cells. Flow cytometry and immunoblot assay data showed that beauvericin suppressed T-cell proliferation, activation and IFN-γ-STAT1-T-bet signaling and subsequently led to apoptosis of activated T cells by suppressing Bcl-2 and phosphorylated Bad as well as increasing cleavage of caspase-3, -9, -12 and PARP. Furthermore, inhibition of PI3K/Akt signaling, which was an upstream regulator of cell activation and survival in activated T cells, contributed to the effect of beauvericin. Overall, these results supported beauvericin as a novel drug candidate for the treatment of colonic inflammation mainly by targeting PI3K/Akt in activated T cells.

  12. Relationship of intestinal flora disorder with TLR/NK-kB and inflammatory mediator expression in patients with ulcerative colitis

    Directory of Open Access Journals (Sweden)

    Ma Tao

    2017-07-01

    Full Text Available Objective: To study the relationship of intestinal flora disorder with TLR/NK-kB and inflammatory mediator expression in patients with ulcerative colitis (UC. Methods: Patients who were diagnosed with UC in Yan’an People’s Hospital between May 2015 and February 2017 were selected, patients with active UC and patients with remission UC were included in the AUC and RUC group; patients who were diagnosed with colonic polyps in Yan’an People’s Hospital through physical examination during the same period were selected as the control group. Feces was collected to test the flora number, mucosa lesion was collected to determine the expression of TLR/NK-kB and inflammatory mediators, and serum was collected to detect the levels of inflammatory mediators. Results: Bifidobacterium, lactobacillus acidophilus and bacteroides number in feces of AUC group and RUC group were significantly lower than those of control group while escherichia coli and enterococcus number in feces, TLR2, TLR4, TLR5, TLR9, NK-kB, HMGB1, TNF-α, IL-6 and IL-17 mRNA expression in intestinal mucosa lesion as well as HMGB1, TNF-α, IL-6 and IL-17 levels in serum were significantly higher than those of control group; bifidobacterium, lactobacillus acidophilus and bacteroides number in feces of AUC group were significantly lower than those of RUC group while escherichia coli and enterococcus number in feces, TLR2, TLR4, TLR5, TLR9, NKkB, HMGB1, TNF-α, IL-6 and IL-17 mRNA expression in intestinal mucosa lesion as well as HMGB1, TNF-α, IL-6 and IL-17 levels in serum were significantly higher than those of RUC group; TLR2, TLR4, TLR5, TLR9, NK-kB, HMGB1, TNF-α, IL-6 and IL-17 mRNA expression in intestinal mucosa lesion as well as HMGB1, TNF-α, IL-6 and IL-17 levels in serum were negatively correlated with bifidobacteria, lactobacillus acidophilus and bacteroides number, and positively correlated with escherichia coli and enterococcus number. Conclusion: The intestinal flora

  13. Dietary supplementation of krill oil attenuates inflammation and oxidative stress in experimental ulcerative colitis in rats.

    Science.gov (United States)

    Grimstad, Tore; Bjørndal, Bodil; Cacabelos, Daniel; Aasprong, Ole Gunnar; Janssen, Emiel A M; Omdal, Roald; Svardal, Asbjørn; Hausken, Trygve; Bohov, Pavol; Portero-Otin, Manuel; Pamplona, Reinald; Berge, Rolf K

    2012-01-01

    To evaluate the effects of krill oil (KO) on inflammation and redox status in dextran sulfate sodium (DSS)-induced colitis in rats. Thirty male Wistar rats were divided into three groups: Control, DSS, and DSS + KO 5% in a 4-week diet study. Colitis was induced by 5% DSS in the drinking water the last week of the experiment. Weight and disease activity index (DAI), colon length, histological combined score (HCS), colon levels of selected cytokines and prostaglandins, markers of protein oxidative damage, fatty acid profile, and expression of selected genes were measured. Rats in the DSS group increased their DAI and HCS compared with healthy controls. The colon length was significantly preserved after KO diet. Tumor necrosis factor (TNF)-α and interleukin (IL)-1β were elevated in the DSS group compared with controls. Cytokines and HCS were nonsignificantly lower in the KO versus the DSS group. Prostaglandin (PG)E(3) increased significantly in the KO versus the other groups. Peroxisome proliferator-activated receptor (PPAR)-γ expression was nonsignificantly increased while PPAR-γ coactivator 1α (Pparg1α) expression increased significantly after KO. The levels of protein oxidation markers decreased significantly. KO showed protective potential against DSS colitis based on the preservation of colon length, reduction of oxidative markers and the consistent beneficial changes of HCS, cytokine, and (PG)E(3) levels, as well as PPAR-γ and Pparg1α expression compared with DSS alone. These findings indicate an anti-inflammatory and a protein antioxidant effect of KO.

  14. Patchouli alcohol ameliorates dextran sodium sulfate-induced experimental colitis and suppresses tryptophan catabolism.

    Science.gov (United States)

    Qu, Chang; Yuan, Zhong-Wen; Yu, Xiu-Ting; Huang, Yan-Feng; Yang, Guang-Hua; Chen, Jian-Nan; Lai, Xiao-Ping; Su, Zi-Ren; Zeng, Hui-Fang; Xie, Ying; Zhang, Xiao-Jun

    2017-07-01

    Despite the increased morbidity of ulcerative colitis (UC) in recent years, available treatments remain unsatisfactory. Pogostemon cablin has been widely applied to treat a variety of gastrointestinal disorders in clinic for centuries, in which patchouli alcohol (PA, C15H26O) has been identified as the major active component. This study attempted to determine the bioactivity of PA on dextran sulfate sodium (DSS)-induced mice colitis and clarify the mechanism of action. Acute colitis was induced in mice by 3% DSS for 7 days. The mice were then given PA (10, 20 and 40mg/kg) or sulfasalazine (SASP, 200mg/kg) as positive control via oral administration for 7 days. At the end of study, animals were sacrificed and samples were collected for pathological and other analysis. In addition, a metabolite profiling and a targeted metabolite analysis, based on the Ultra-Performance Liquid Chromatography coupled with mass spectrometry (UPLC-MS) approach, were performed to characterize the metabolic changes in plasma. The results revealed that PA significantly reduced the disease activity index (DAI) and ameliorated the colonic injury of DSS mice. The levels of colonic MPO and cytokines involving TNF-α, IFN-γ, IL-1β, IL-6, IL-4 and IL-10 also declined. Furthermore, PA improved the intestinal epithelial barrier by enhancing the level of colonic expression of the tight junction (TJ) proteins, for instance ZO-1, ZO-2, claudin-1 and occludin, and by elevating the levels of mucin-1 and mucin-2 mRNA. The study also demonstrated that PA inhibited the DSS-induced cell death signaling by modulating the apoptosis related Bax and Bcl-2 proteins and down-regulating the necroptosis related RIP3 and MLKL proteins. By comparison, up-regulation of IDO-1 and TPH-1 protein expression in DSS group was suppressed by PA, which was in line with the declined levels of kynurenine (Kyn) and 5-hydroxytryptophan (5-HTP) in plasma. The therapeutic effect of PA was evidently reduced when Kyn was given to

  15. STAT3 activation in Th17 and Th22 cells controls IL-22-mediated epithelial host defense during infectious colitis.

    Science.gov (United States)

    Backert, Ingo; Koralov, Sergei B; Wirtz, Stefan; Kitowski, Vera; Billmeier, Ulrike; Martini, Eva; Hofmann, Katharina; Hildner, Kai; Wittkopf, Nadine; Brecht, Katrin; Waldner, Maximilian; Rajewsky, Klaus; Neurath, Markus F; Becker, Christoph; Neufert, Clemens

    2014-10-01

    The Citrobacter rodentium model mimics the pathogenesis of infectious colitis and requires sequential contributions from different immune cell populations, including innate lymphoid cells (ILCs) and CD4(+) lymphocytes. In this study, we addressed the role of STAT3 activation in CD4(+) cells during host defense in mice against C. rodentium. In mice with defective STAT3 in CD4(+) cells (Stat3(ΔCD4)), the course of infection was unchanged during the innate lymphoid cell-dependent early phase, but significantly altered during the lymphocyte-dependent later phase. Stat3(ΔCD4) mice exhibited intestinal epithelial barrier defects, including downregulation of antimicrobial peptides, increased systemic distribution of bacteria, and prolonged reduction in the overall burden of C. rodentium infection. Immunomonitoring of lamina propria cells revealed loss of virtually all IL-22-producing CD4(+) lymphocytes, suggesting that STAT3 activation was required for IL-22 production not only in Th17 cells, but also in Th22 cells. Notably, the defective host defense against C. rodentium in Stat3(∆CD4) mice could be fully restored by specific overexpression of IL-22 through a minicircle vector-based technology. Moreover, expression of a constitutive active STAT3 in CD4(+) cells shaped strong intestinal epithelial barrier function in vitro and in vivo through IL-22, and it promoted protection from enteropathogenic bacteria. Thus, our work indicates a critical role of STAT3 activation in Th17 and Th22 cells for control of the IL-22-mediated host defense, and strategies expanding STAT3-activated CD4(+) lymphocytes may be considered as future therapeutic options for improving intestinal barrier function in infectious colitis. Copyright © 2014 by The American Association of Immunologists, Inc.

  16. Glutathione peroxidase 2 and aquaporin 8 as new markers for colonic inflammation in experimental colitis and inflammatory bowel diseases: an important role for H2O2?

    NARCIS (Netherlands)

    te Velde, Anje A.; Pronk, Inge; de Kort, Floor; Stokkers, Pieter C. F.

    2008-01-01

    Objective Different mouse models of inflammatory bowel diseases IBD demonstrate various aspects of the pathophysiology of IBD. We looked for overlapping gene expression profiles in three different mouse models of experimental colitis and analysed whether these overlapping genes are of help to find

  17. Effect of Concentrated Apple Extract on Experimental Colitis Induced by Acetic Acid.

    Science.gov (United States)

    Pastrelo, Maurício Mercaldi; Dias Ribeiro, Carla Caroline; Duarte, Joselmo Willamys; Bioago Gollücke, Andréa Pitelli; Artigiani-Neto, Ricardo; Ribeiro, Daniel Araki; Miszputen, Sender Jankiel; Fujiyama Oshima, Celina Tizuko; Ribeiro Paiotti, Ana Paula

    2017-01-01

    Reactive oxygen and nitrogen species (ROS/RNS) play a crucial role in inflammatory bowel disease (IBD) exacerbating the chronic inflammatory process. Endogenous and diet antioxidants can neutralize these compounds. The apple is widely consumed, with several antioxidant activity compounds. The present study evaluated the effects of concentrated apple extract (CAE) in acetic acid induced colitis. 29 Wistar male rats were randomized into 5 groups. G1-Sham/saline solution, G2-CAE/control, G3-acetic acid/control, G4-curative- CAE treatment and G5-preventive-CAE treatment. Eight days later, the animals were euthanized and the colonic segment resected for macroscopic and histological analysis. Gene expression was evaluated for inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), catalase and copper and zinc superoxide dismutase (CuZnSOD) by quantitative real time PCR, while protein expression was assessed for iNOS, COX-2 and 8-hydroxy-20-deoxyguanosine (8-OHdG) via immunohistochemistry. The groups G3, G4 and G5 had weight loss, while G5 had weight increase at the end of the experiment. The treatment with CAE reduced the macroscopic and microscopic injury, decreased iNOS mRNA expression and increased CuZnSOD mRNA expression in animals with induced acetic acid-colitis. The findings of the present study suggest that CAE treatment exerts an antioxidant role by downregulating iNOS and upregulating CuZnSOD.

  18. Biodistribution and Efficacy of Human Adipose-Derived Mesenchymal Stem Cells Following Intranodal Administration in Experimental Colitis

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    Mercedes Lopez-Santalla

    2017-06-01

    Full Text Available Mesenchymal stem cells (MSCs have a large potential in cell therapy for treatment of inflammatory and autoimmune diseases, thanks to their immunomodulatory properties. The encouraging results in animal models have initiated the translation of MSC therapy to clinical trials. In cell therapy protocols with MSCs, administered intravenously, several studies have shown that a small proportion of infused MSCs can traffic to the draining lymph nodes (LNs. This is accompanied with an increase of different types of regulatory immune cells in the LNs, suggesting the importance of migration of MSCs to the LNs in order to contribute to immunomodulatory response. Intranodal (IN, also referred as intralymphatic, injection of cells, like dendritic cells, is being proposed in the clinic for the treatment of cancer and allergy, showing that this route of administration is clinically safe and efficient. In this study, we investigated, for the first time, the biodistribution and the efficacy of Luciferase+ adipose-derived MSCs (Luci-eASCs, infused through the inguinal LNs (iLNs, in normal mice and in inflamed mice with colitis. Most of the Luci-eASCs remain in the iLNs and in the adipose tissue surrounding the inguinal LNs. A small proportion of Luci-eASCs can migrate to other locations within the lymphatic system and to other tissues and organs, having a preferential migration toward the intestine in colitic mice. Our results show that the infused Luci-eASCs protected 58% of the mice against induced colitis. Importantly, a correlation between the response to eASC treatment and a higher accumulation of eASCs in popliteal, parathymic, parathyroid, and mesenteric LNs were found. Altogether, these results suggest that IN administration of eASCs is feasible and may represent an effective strategy for cell therapy protocols with human adipose-derived MSCs in the clinic for the treatment of immune-mediated disorders.

  19. Zanthoxylum bungeanum pericarp extract prevents dextran sulfate sodium-induced experimental colitis in mice via the regulation of TLR4 and TLR4-related signaling pathways.

    Science.gov (United States)

    Zhang, Zecai; Liu, Jiuxi; Shen, Peng; Cao, Yongguo; Lu, Xiaojie; Gao, Xuejiao; Fu, Yunhe; Liu, Bo; Zhang, Naisheng

    2016-12-01

    Zanthoxylum bungeanum, which belongs to the Zanthoxylum genus of the Rutaceae family, is now wildly distributed in most parts of China and some Southeast Asian countries. The pericarp of Zanthoxylum bungeanum has been known to exhibit antibacterial, anti-inflammatory and other important therapeutic activities. The purpose of this study was to investigate the effects and mechanisms of Zanthoxylum bungeanum pericarp extract (ZBE) on DSS-induced experimental colitis in mice. The results demonstrated that the major flavonoid composition of ZBE includes rutin (32.36%), quercetin (13.61%) and isoquercitrin (24.89%). ZBE alleviated DSS-induced body weight loss, colon length shortening and colonic pathological damage. Furthermore, ZBE inhibited the expression of TNF-α, IL-1β and IL-12 via the regulation of TLR4 and TLR4-related pathways in DSS-induced experimental colitis in mice and LPS-triggered inflammation in J774.1 cells. Our findings suggest that ZBE is effective in ameliorating experimental colitis, and further investigation is necessary on the use of ZBE as a new dietary strategy to lower the risk of ulcerative colitis (UC). Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Reproduction of mucohaemorrhagic diarrhea and colitis indistinguishable from swine dysentery following experimental inoculation with "Brachyspira hampsonii" strain 30446.

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    Joseph E Rubin

    Full Text Available BACKGROUND: Mucohaemorrhagic diarrhea caused by Brachyspira hyodysenteriae, swine dysentery, is a severe production limiting disease of swine. Recently, pigs in western Canada with clinical signs indistinguishable from swine dysentery were observed. Despite the presence of spirochetes on fecal smears, recognized Brachyspira spp. including B. hyodysenteriae could not be identified. A phylogenetically distinct Brachyspira, called "B. hampsonii" strain 30446, however was isolated. The purpose of this study was to experimentally reproduce mucohaemorrhagic colitis and characterize strain 30446 shedding following inoculation. METHODS AND FINDINGS: Eighteen 13-week-old pigs were randomly assigned to inoculation (n = 12 or control (n = 6 groups in each of two trials. In trial 1, pigs were inoculated with a tissue homogenate collected from clinically affected field cases. In trial 2, pigs were inoculated with a pure broth culture of strain 30446. In both trials, mucohaemorrhagic diarrhea was significantly more common in inoculated pigs than controls, all of which remained healthy. In animals with mucohaemorrhagic diarrhea, significantly more spirochetes were observed on Gram stained fecal smears, and higher numbers of strain 30446 genome equivalents were detected by quantitative PCR (qPCR. Strain 30446 was cultured from colon and/or feces of all affected but no control animals at necropsy. CONCLUSIONS: "Brachyspira hampsonii" strain 30446 causes mucohaemorrhagic diarrhea in pigs following a 4-9 day incubation period. Fecal shedding was detectable by day 4 post inoculation, and rarely preceded the onset of mucoid or haemorrhagic diarrhea by more than 2 days. Culture and 30446-specific qPCR are reliable methods of detection of this organism in feces and tissues of diarrheic pigs. The emergence of a novel Brachyspira spp., such as "B. hampsonii", creates diagnostic challenges including higher risk of false negative diagnostic tests. We therefore

  1. Reproduction of Mucohaemorrhagic Diarrhea and Colitis Indistinguishable from Swine Dysentery following Experimental Inoculation with “Brachyspira hampsonii” Strain 30446

    Science.gov (United States)

    Rubin, Joseph E.; Costa, Matheus O.; Hill, Janet E.; Kittrell, Heather E.; Fernando, Champika; Huang, Yanyun; O’Connor, Brendan; Harding, John C. S.

    2013-01-01

    Background Mucohaemorrhagic diarrhea caused by Brachyspira hyodysenteriae, swine dysentery, is a severe production limiting disease of swine. Recently, pigs in western Canada with clinical signs indistinguishable from swine dysentery were observed. Despite the presence of spirochetes on fecal smears, recognized Brachyspira spp. including B. hyodysenteriae could not be identified. A phylogenetically distinct Brachyspira, called “B. hampsonii” strain 30446, however was isolated. The purpose of this study was to experimentally reproduce mucohaemorrhagic colitis and characterize strain 30446 shedding following inoculation. Methods and Findings Eighteen 13-week-old pigs were randomly assigned to inoculation (n = 12) or control (n = 6) groups in each of two trials. In trial 1, pigs were inoculated with a tissue homogenate collected from clinically affected field cases. In trial 2, pigs were inoculated with a pure broth culture of strain 30446. In both trials, mucohaemorrhagic diarrhea was significantly more common in inoculated pigs than controls, all of which remained healthy. In animals with mucohaemorrhagic diarrhea, significantly more spirochetes were observed on Gram stained fecal smears, and higher numbers of strain 30446 genome equivalents were detected by quantitative PCR (qPCR). Strain 30446 was cultured from colon and/or feces of all affected but no control animals at necropsy. Conclusions “Brachyspira hampsonii” strain 30446 causes mucohaemorrhagic diarrhea in pigs following a 4–9 day incubation period. Fecal shedding was detectable by day 4 post inoculation, and rarely preceded the onset of mucoid or haemorrhagic diarrhea by more than 2 days. Culture and 30446-specific qPCR are reliable methods of detection of this organism in feces and tissues of diarrheic pigs. The emergence of a novel Brachyspira spp., such as “B. hampsonii”, creates diagnostic challenges including higher risk of false negative diagnostic tests. We therefore recommend

  2. Reproduction of mucohaemorrhagic diarrhea and colitis indistinguishable from swine dysentery following experimental inoculation with "Brachyspira hampsonii" strain 30446.

    Science.gov (United States)

    Rubin, Joseph E; Costa, Matheus O; Hill, Janet E; Kittrell, Heather E; Fernando, Champika; Huang, Yanyun; O'Connor, Brendan; Harding, John C S

    2013-01-01

    Mucohaemorrhagic diarrhea caused by Brachyspira hyodysenteriae, swine dysentery, is a severe production limiting disease of swine. Recently, pigs in western Canada with clinical signs indistinguishable from swine dysentery were observed. Despite the presence of spirochetes on fecal smears, recognized Brachyspira spp. including B. hyodysenteriae could not be identified. A phylogenetically distinct Brachyspira, called "B. hampsonii" strain 30446, however was isolated. The purpose of this study was to experimentally reproduce mucohaemorrhagic colitis and characterize strain 30446 shedding following inoculation. Eighteen 13-week-old pigs were randomly assigned to inoculation (n = 12) or control (n = 6) groups in each of two trials. In trial 1, pigs were inoculated with a tissue homogenate collected from clinically affected field cases. In trial 2, pigs were inoculated with a pure broth culture of strain 30446. In both trials, mucohaemorrhagic diarrhea was significantly more common in inoculated pigs than controls, all of which remained healthy. In animals with mucohaemorrhagic diarrhea, significantly more spirochetes were observed on Gram stained fecal smears, and higher numbers of strain 30446 genome equivalents were detected by quantitative PCR (qPCR). Strain 30446 was cultured from colon and/or feces of all affected but no control animals at necropsy. "Brachyspira hampsonii" strain 30446 causes mucohaemorrhagic diarrhea in pigs following a 4-9 day incubation period. Fecal shedding was detectable by day 4 post inoculation, and rarely preceded the onset of mucoid or haemorrhagic diarrhea by more than 2 days. Culture and 30446-specific qPCR are reliable methods of detection of this organism in feces and tissues of diarrheic pigs. The emergence of a novel Brachyspira spp., such as "B. hampsonii", creates diagnostic challenges including higher risk of false negative diagnostic tests. We therefore recommend diagnostic laboratories routinely use Brachyspira culture

  3. The majority of lamina propria CD4(+) T-cells from scid mice with colitis undergo Fas-mediated apoptosis in vivo

    DEFF Research Database (Denmark)

    Bregenholt, S; Petersen, T R; Claesson, Mogens Helweg

    2001-01-01

    We have previously shown that adoptively transferred CD4(+) T-cells mediate an chronic colitis in severe combined immune deficient (scid) mice. Colitis is accompanied by activation and apoptosis of Fas ligand and TNF-alpha expressing CD4(+) T-cells in the diseased colonic lamina propria (Eur. J....... Immunol. 28:3655 (1998)). Here we investigate the apoptosis-inducing mechanism in these lamina propria infiltrating CD4(+) T-cells. We observe that freshly isolated lamina propria CD4(+) T-cells can kill Fas transfected P815 mastocytoma cells in a TCR/CD3 redirected chromium-release assay, but do...... not express TNF-alpha mediated cytotoxicity. Pre-incubation of the isolated lamina propria CD4(+) T-cells with an anti-FasL antiserum partially blocked killing of the Fas transfected target cells, indicating a role for the Fas-FasL system in the killing process. Treatment of scid mice with colitis with anti...

  4. The role of prostaglandin E2 (PGE 2 in toll-like receptor 4 (TLR4-mediated colitis-associated neoplasia

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    Hayes Lory A

    2010-07-01

    Full Text Available Abstract Background We have previously found that TLR4-deficient (TLR4-/- mice demonstrate decreased expression of mucosal PGE 2 and are protected against colitis-associated neoplasia. However, it is still unclear whether PGE 2 is the central factor downstream of TLR4 signaling that promotes intestinal tumorigenesis. To further elucidate critical downstream pathways involving TLR4-mediated intestinal tumorigenesis, we examined the effects of exogenously administered PGE 2 in TLR4-/- mice to see if PGE 2 bypasses the protection from colitis-associated tumorigenesis. Method Mouse colitis-associated neoplasia was induced by azoxymethane (AOM injection followed by two cycles of dextran sodium sulfate (DSS treatment. Two different doses of PGE 2 (high dose group, 200 μg, n = 8; and low dose group, 100 μg, n = 6 were administered daily during recovery period of colitis by gavage feeding. Another group was given PGE 2 during DSS treatment (200 μg, n = 5. Inflammation and dysplasia were assessed histologically. Mucosal Cox-2 and amphiregulin (AR expression, prostanoid synthesis, and EGFR activation were analyzed. Results In control mice treated with PBS, the average number of tumors was greater in WT mice (n = 13 than in TLR4-/- mice (n = 7. High dose but not low dose PGE 2 treatment caused an increase in epithelial proliferation. 28.6% of PBS-treated TLR4-/- mice developed dysplasia (tumors/animal: 0.4 ± 0.2. By contrast, 75.0% (tumors/animal: 1.5 ± 1.2, P 2 treatment. Endogenous prostanoid synthesis was differentially affected by PGE 2 treatment during acute and recovery phases of colitis. Exogenous administration of PGE 2 increased colitis-associated tumorigenesis but this only occurred during the recovery phase. Lastly, PGE 2 treatment increased mucosal expression of AR and Cox-2, thus inducing EGFR activation and forming a positive feedback mechanism to amplify mucosal Cox-2. Conclusions These results highlight the importance of PGE 2 as a

  5. gp130-mediated Stat3 activation in enterocytes regulates cell survival and cell-cycle progression during colitis-associated tumorigenesis.

    Science.gov (United States)

    Bollrath, Julia; Phesse, Toby J; von Burstin, Vivian A; Putoczki, Tracy; Bennecke, Moritz; Bateman, Trudie; Nebelsiek, Tim; Lundgren-May, Therese; Canli, Ozge; Schwitalla, Sarah; Matthews, Vance; Schmid, Roland M; Kirchner, Thomas; Arkan, Melek C; Ernst, Matthias; Greten, Florian R

    2009-02-03

    Although gastrointestinal cancers are frequently associated with chronic inflammation, the underlying molecular links have not been comprehensively deciphered. Using loss- and gain-of-function mice in a colitis-associated cancer model, we establish here a link comprising the gp130/Stat3 transcription factor signaling axis. Mutagen-induced tumor growth and multiplicity are reduced following intestinal epithelial cell (IEC)-specific Stat3 ablation, while its hyperactivation promotes tumor incidence and growth. Conversely, IEC-specific Stat3 deficiency enhances susceptibility to chemically induced epithelial damage and subsequent mucosal inflammation, while excessive Stat3 activation confers resistance to colitis. Stat3 has the capacity to mediate IL-6- and IL-11-dependent IEC survival and to promote proliferation through G1 and G2/M cell-cycle progression as the common tumor cell-autonomous mechanism that bridges chronic inflammation to tumor promotion.

  6. Role of heat shock protein 47 in intestinal fibrosis of experimental colitis.

    Science.gov (United States)

    Kitamura, Hiroshi; Yamamoto, Shuji; Nakase, Hiroshi; Matsuura, Minoru; Honzawa, Yusuke; Matsumura, Kayoko; Takeda, Yasuhiro; Uza, Norimitsu; Nagata, Kazuhiro; Chiba, Tsutomu

    2011-01-14

    Intestinal fibrosis is a clinically important issue of inflammatory bowel disease (IBD). It is unclear whether or not heat shock protein 47 (HSP47), a collagen-specific molecular chaperone, plays a critical role in intestinal fibrosis. The aim of this study is to investigate the role of HSP47 in intestinal fibrosis of murine colitis. HSP47 expression and localization were evaluated in interleukin-10 knockout (IL-10KO) and wild-type (WT, C57BL/6) mice by immunohistochemistry. Expression of HSP47 and transforming growth factor-β1 (TGF-β1) in colonic tissue was measured. In vitro studies were conducted in NIH/3T3 cells and primary culture of myofibroblasts separated from colonic tissue of IL-10KO (PMF KO) and WT mice (PMF WT) with stimulation of several cytokines. We evaluated the inhibitory effect of administration of small interfering RNA (siRNA) targeting HSP47 on intestinal fibrosis in IL-10KO mice in vivo. Immunohistochemistry revealed HSP47 positive cells were observed in the mesenchymal and submucosal area of both WT and IL-10 KO mice. Gene expressions of HSP47 and TGF-β1 were significantly higher in IL-10KO mice than in WT mice and correlated with the severity of inflammation. In vitro experiments with NIH3T3 cells, TGF-β1 only induced HSP47 gene expression. There was a significant difference of HSP47 gene expression between PMF KO and PMF WT. Administration of siRNA targeting HSP47 remarkably reduced collagen deposition in colonic tissue of IL-10KO mice. Our results indicate that HSP47 plays an essential role in intestinal fibrosis of IL-10KO mice, and may be a potential target for intestinal fibrosis associated with IBD. Copyright © 2010 Elsevier Inc. All rights reserved.

  7. Oral Grapeseed Oil and Sesame Oil in Experimental Acetic Acid-Induced Ulcerative Colitis in Rat

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    Hosseinzadeh

    2016-06-01

    Full Text Available Background Ulcerative colitis (UC is a multi-factorial disease with unknown etiology and has many clinical manifestations. Objectives The current study aimed to evaluate the effects of sesame oil (SO and grapeseed oil (GSO on acetic acid-induced UC in rats. Materials and Methods Eighty male rats were divided into eight groups as health control (HC1, received normal saline; HC2, received SO; HC3, received GSO; negative control (NC, UC and normal saline; positive control (PC, UC and mesalamine; SO, UC and SO; GSO, UC and GSO, and SO + GSO. The daily weight changes, serum levels of oxidative stress markers and lipid profile plus colon macroscopic and microscopic histological changes were measured at the end of the seventh day. Results Significant differences were detected between HC1 and PC on the 3rd (P = 0.002, 4th (0.013 and 6th days (0.014 and between HC1 and NC on the 4th day (0.027 in weight of rats. Use of GSO alone or in combination with SO decreased the extent of the changes both in macroscopic and microscopic indices and also at the inflammation level. The most significant decrease in the MDA level and the most obvious increase in the TAC belonged to the GSO group in comparison to the NC group. The lowest cholesterol (51.43 ± 5.62 mg/dL and HDL levels (29.29 ± 6.24 mg/dL were detected in response to SO consumption in comparison to NC group (P = 0.030 and P = 0.257, respectively. Conclusions GSO in combination with SO may be considered as the treatment of choice for UC based on antioxidant and histopathological evaluations.

  8. Thermal spring water drinking attenuates dextran-sulfate-sodium-induced colitis in mice.

    Science.gov (United States)

    Pozsgai, Gábor; Benkó, Rita; Barthó, Loránd; Horváth, Katalin; Pintér, Erika

    2015-02-01

    The present study investigates the effect of oral consumption of hydrogen sulfide-containing Harkány thermal spring water, as well as sodium hydrogen sulfide (NaHS) solution on experimental colitis. Colitis was induced by 2% dextran sulfate sodium (DSS) in the drinking water of C57BL/6 mice for 7 days. Some animal groups drank Harkány thermal spring water or water supplemented with 21.68 mg/L NaHS. General signs of colitis, myeloperoxidase (MPO) enzyme activity of colon samples, histological features of colitis and function of the enteric nervous system were assessed. Oral administration of Harkány thermal spring water significantly attenuated general signs of colitis, MPO enzyme activity of colon samples and detrimental effect of colitis on the function of the enteric nervous system, but not histological signs of colitis. These findings could be reproduced using NaHS solution with additional significantly diminished histological damage. We conclude that oral treatment with Harkány thermal spring water relieves various aspects of DSS-evoked colitis in mice. This effect is most likely to be mediated by hydrogen sulfide content of the Harkány water. Our data might promote complementary utilization of sulfurous thermal spring water in the therapy of inflammatory bowel disease.

  9. 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...

  10. Comparative Protective Effect of Hawthorn Berry Hydroalcoholic Extract, Atorvastatin, and Mesalamine on Experimentally Induced Colitis in Rats

    Science.gov (United States)

    Shafie-Irannejad, Vahid; Hobbenaghi, Rahim; Tabatabaie, Seyed Hamed; Moshtaghion, Seyed-Mehdi

    2013-01-01

    Abstract The protective effect of hydroalcoholic extract of hawthorn berries (HBE) on acetic acid (AA)–induced colitis in rats was investigated. Forty-two Wistar rats were divided into seven groups, including control and test groups (n=6). The control animals received saline, and the test animals were treated with saline (sham group), mesalamine (50 mg/kg; M group), atorvastatin (20 mg/kg; A group), HBE (100 mg/kg; H group), mesalamine and HBE (HM group), or atorvastatin plus HBE (HA group), 3 days before and a week after colitis induction. Colitis was induced by administration of 1 mL AA (4%) via a polyethylene catheter intrarectally. High-performance liquid chromatography analyses showed that HBE contained 0.13% and 0.5% oleanolic acid and ursolic acid, respectively. Elevated myeloperoxidase activity and lipid peroxidation were attenuated in the HA group. The H and HM groups showed marked reductions in colitis-induced decreases in total thiol molecules and body weight. The histopathological studies revealed that HBE decreased colitis-induced edema and infiltration of neutrophils. Our data suggest the anti-inflammatory and antioxidant effects of HBE and atorvastatin protect against AA-induced colitis. The anti-inflammatory effect of HBE may be attributable to its ability to decrease myeloperoxidase activity as a biomarker of neutrophil infiltration. PMID:23875899

  11. Submucosal neurons and enteric glial cells expressing the P2X7 receptor in rat experimental colitis.

    Science.gov (United States)

    da Silva, Marcos Vinícius; Marosti, Aline Rosa; Mendes, Cristina Eusébio; Palombit, Kelly; Castelucci, Patricia

    2017-06-01

    The aim of this study was to evaluate the effect of ulcerative colitis on the submucosal neurons and glial cells of the submucosal ganglia of rats. 2,4,6-Trinitrobenzene sulfonic acid (TNBS; colitis group) was administered in the colon to induce ulcerative colitis, and distal colons were collected after 24h. The colitis rats were compared with those in the sham and control groups. Double labelling of the P2X7 receptor with calbindin (marker for intrinsic primary afferent neurons, IPANs, submucosal plexus), calretinin (marker for secretory and vasodilator neurons of the submucosal plexus), HuC/D and S100β was performed in the submucosal plexus. The density (neurons per area) of submucosal neurons positive for the P2X7 receptor, calbindin, calretinin and HuC/D decreased by 21%, 34%, 8.2% and 28%, respectively, in the treated group. In addition, the density of enteric glial cells in the submucosal plexus decreased by 33%. The profile areas of calbindin-immunoreactive neurons decreased by 25%. Histological analysis revealed increased lamina propria and decreased collagen in the colitis group. This study demonstrated that ulcerative colitis affected secretory and vasodilatory neurons, IPANs and enteric glia of the submucosal plexus expressing the P2X7 receptor. Copyright © 2017 Elsevier GmbH. All rights reserved.

  12. Enteric Glia Mediate Neuron Death in Colitis Through Purinergic Pathways That Require Connexin-43 and Nitric OxideSummary

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    Isola A.M. Brown

    2016-01-01

    Full Text Available Background & Aims: The concept of enteric glia as regulators of intestinal homeostasis is slowly gaining acceptance as a central concept in neurogastroenterology. Yet how glia contribute to intestinal disease is still poorly understood. Purines generated during inflammation drive enteric neuron death by activating neuronal P2X7 purine receptors (P2X7R; triggering adenosine triphosphate (ATP release via neuronal pannexin-1 channels that subsequently recruits intracellular calcium ([Ca2+]i in surrounding enteric glia. We tested the hypothesis that the activation of enteric glia contributes to neuron death during inflammation. Methods: We studied neuroinflammation in vivo using the 2,4-dinitrobenzene sulfonic acid model of colitis and in situ using whole-mount preparations of human and mouse intestine. Transgenic mice with a targeted deletion of glial connexin-43 (Cx43 [GFAP::CreERT2+/−/Cx43f/f] were used to specifically disrupt glial signaling pathways. Mice deficient in inducible nitric oxide (NO synthase (iNOS−/− were used to study NO production. Protein expression and oxidative stress were measured using immunohistochemistry and in situ Ca2+ and NO imaging were used to monitor glial [Ca2+]i and [NO]i. Results: Purinergic activation of enteric glia drove [Ca2+]i responses and enteric neuron death through a Cx43-dependent mechanism. Neurotoxic Cx43 activity, driven by NO production from glial iNOS, was required for neuron death. Glial Cx43 opening liberated ATP and Cx43-dependent ATP release was potentiated by NO. Conclusions: Our results show that the activation of glial cells in the context of neuroinflammation kills enteric neurons. Mediators of inflammation that include ATP and NO activate neurotoxic pathways that converge on glial Cx43 hemichannels. The glial response to inflammatory mediators might contribute to the development of motility disorders. Keywords: Enteric Nervous System, Hemichannels

  13. Altered gp130 signalling ameliorates experimental colitis via myeloid cell-specific STAT3 activation and myeloid-derived suppressor cells

    Science.gov (United States)

    Däbritz, Jan; Judd, Louise M.; Chalinor, Heather V.; Menheniott, Trevelyan R.; Giraud, Andrew S.

    2016-01-01

    STAT3 regulates the expansion of myeloid-derived suppressor cells (MDSCs) during inflammation, infection and cancer. Hyperactivation of STAT3 in gp130757F/F mice is associated with protection from experimental colitis. This study determined mechanisms for this protection and compared this to mice with myeloid-specific STAT3-deficiency (LysMcre/STAT3flox; gp130757F/F LysMcre/STAT3flox). Acute and chronic colitis was induced and colons were removed for histological, mRNA and protein analysis. Cell populations from spleen, mesenteric lymph node and colon were analyzed for different myeloid cell populations using flow cytometry. Functions of MDSCs and LPS-stimulated peritoneal macrophages were further characterized by in vitro and in vivo assays. Here we show that the resistance to experimental colitis in gp130757F/F mice is via myeloid-cell specific STAT3 activation, MDSC expansion and increased production of suppressive and protective cytokines. PMID:26848037

  14. Involvement of 5HT3 Receptors in Anti-Inflammatory Effects of Tropisetron on Experimental TNBS-Induced Colitis in Rat

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    Azadeh Motavallian

    2013-12-01

    Full Text Available Introduction: There is a pressing need for research leading to the development of new effective drugs with lower side effects and more efficacy for treating inflammatory bowel disease (IBD. The analgesic and anti-inflammatory properties of 5-Hydroxytryptamine (5-HT-3 receptor antagonists have been shown in in vivo and in vitro studies. The present study was designed to investigate the effects of tropisetron, a 5-HT3 receptor antagonist, on an immune-based animal model of IBD. Methods: In the present study, the trinitrobenzenesulfonic acid (TNBS model of colitis in the rat was used. Two hours after induction of colitis in rats, tropisetron (2 mg/kg, dexamethasone (1 mg/kg, meta-chlorophenylbiguanide (mCPBG, 5 mg/kg, a 5-HT3 receptor agonist, or tropisetron + mCPBG were intraperitoneally (i.p. administrated for 6 days. Animals were then sacrificed; macroscopic, histological, biochemical (myeloperoxidase [MPO] assessments and ELISA test (tumor necrosis factor-alpha, interleukin-6 and interleukin-1 beta were performed on distal colon samples. Results: Tropisetron or dexamethasone treatment significantly reduced macroscopic and microscopic colonic damages. In addition, a significant reduction in MPO activity and colonic levels of inflammatory cytokines was seen. The beneficial effects of tropisetron were antagonized by concurrent administration of mCPBG. Conclusion: The present study indicates that the protective effects of tropisetron on TNBS-induced colitis can be mediated by 5-HT3 receptors.

  15. Association of Serotonin Transporter Promoter Polymorphism (5-HTTLPR) with Microscopic Colitis and Ulcerative Colitis.

    Science.gov (United States)

    Sikander, Arbab; Sinha, Saroj Kant; Prasad, Kaushal Kishor; Rana, Satya Vati

    2015-04-01

    Serotonin (5-HT) release and serotonin reuptake transporter (5-HTT) expression have been reported to be decreased in experimental colitis, in interleukin-10 knockout-associated colitis, and in patients with ulcerative colitis. Serotonin is known to play an important role in the pathogenesis of colitis, but individual genetic variants of 5-HTT gene in microscopic colitis and ulcerative colitis are not known. This study aimed to evaluate the association between the serotonin transporter gene promoter polymorphism (5-HTTLPR) and 5-HT concentration in microscopic colitis (MC) and ulcerative colitis (UC) patients. This prospective case-control study included 41 patients with microscopic colitis (age 19-82 years, mean 35 ± 13.6), 75 patients with ulcerative colitis (age 16-65 years, mean 38.5 ± 11.6), and 100 controls (age 20-64 years, mean 38 ± 11). 5-HTTLPR gene polymorphism was studied by polymerase chain reaction-based assay. 5-HT levels were measured by ELISA. The frequency of the 5-HTTLPR (SS) genotype was significantly lower in MC (12 %) patients compared to controls (30 %) (p microscopic colitis, suggesting that 5-HTTLPR is a potential candidate gene involved in the pathogenesis of microscopic colitis. Serotonin levels were significantly higher in microscopic colitis and ulcerative colitis patients compared to healthy controls.

  16. Anti-inflammatory and immunomodulatory effects of Spirulina platensis in comparison to Dunaliella salina in acetic acid-induced rat experimental colitis.

    Science.gov (United States)

    Abdel-Daim, Mohamed M; Farouk, Sameh M; Madkour, Fedekar F; Azab, Samar S

    2015-04-01

    Spirulina platensis (SP) is used as a source of protein and vitamin supplement in humans without any significant side-effects. Dunaliella salina (DS) is also regarded as one of the richest natural producers of carotenoid, thus used as a source of antioxidants to protect cells from oxidative damage. The aim of the present study is to compare the ameliorative effect of Spirulina and Dunaliella in experimental colitis. Spirulina and Dunaliella were investigated at the same dose of 500 mg/kg body weight for their modulatory effect against acetic-acid induced ulcerative colitis (UC) in rats. The colonic lesion was analyzed by examining macroscopic damage, bloody diarrhea scores, colon weight/length and change in body weight of tested rats. Colon lipid peroxidation and oxidative stress markers were examined by evaluating malondialdehyde (MDA), protein carbonyl (PCO), catalase (CAT), reduced glutathione (GSH) and superoxide dismutase (SOD). Colon inflammatory markers; myeloperoxidase (MPO) and prostaglandin (PGE2) as well as proinflammatory cytokines; tumor necrosis factor (TNF-α) and interleukins (IL-1β, IL-6) were also studied. The colonic mucosal injury, biochemical and histopathologic results suggest that both SP and DS exhibit significant modulatory effect on acetic acid-induced colitis in rats, which may be due to a significant increase of antioxidant enzymes activity and significant inhibition of lipid peroxidation and inflammation markers. Results showed that in comparison to Sulfasalazine, SP exhibited better therapeutic and safety profile than DS against acetic acid-induced UC. This study suggests potential benefits of SP and DS in an experimental model of colitis.

  17. Actual Usage and Quality of Experimental Colitis Models in Preclinical Efficacy Testing: A Scoping Review

    NARCIS (Netherlands)

    Zeeff, S.B.; Kunne, C.; Bouma, G.; Vries, R.B.M. de; Velde, A.A. Te

    2016-01-01

    BACKGROUND: There is no standardized validated experimental model used to predict human drug response, and the choice of model is not based on systematic evidence. Therefore, we decided to systematically investigate which models are currently used by selecting studies from literature that use

  18. Actual Usage and Quality of Experimental Colitis Models in Preclinical Efficacy Testing: A Scoping Review

    NARCIS (Netherlands)

    Zeeff, Sophia B.; Kunne, Cindy; Bouma, Gerd; de Vries, Rob B.; te Velde, Anje A.

    2016-01-01

    Background:There is no standardized validated experimental model used to predict human drug response, and the choice of model is not based on systematic evidence. Therefore, we decided to systematically investigate which models are currently used by selecting studies from literature that use

  19. 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.

  20. Experimental and Pathalogical study of Pistacia atlantica, butyrate, Lactobacillus casei and their combination on rat ulcerative colitis model.

    Science.gov (United States)

    Gholami, Mahdi; Ghasemi-Niri, Seyedeh Farnaz; Maqbool, Faheem; Baeeri, Maryam; Memariani, Zahra; Pousti, Iraj; Abdollahi, Mohammad

    2016-06-01

    This study evaluated the effects of Pistacia atlantica (P. atlantica), butyrate, Lactobacillus casei (L. casei) and especially their combination therapy on 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced rat colitis model. Rats were divided into seven groups. Four groups received oral P. atlantica, butyrate, L. casei and the combination of three agents for 10 consecutive days. The remaining groups were negative and positive controls and a sham group. Macroscopic and histopathological examinations were carried out along with determination of the specific biomarker of colonic oxidative stress, the myeloperoxidase (MPO). Compared with controls, the combination therapy exhibited a significant alleviation of colitis in terms of pathological scores and reduction of MPO activity (55%, p=0.0009). Meanwhile, the macroscopic appearance such as stool consistency, tissue and histopathological scores (edema, necrosis and neutrophil infiltration) were improved. Although single therapy by each P. atlantica, butyrate, and L. casei was partially beneficial in reduction of colon oxidative stress markers, the combination therapy was much more effective. In conclusion, the combination therapy was able to reduce the severity of colitis that is clear from biochemical markers. Future studies have to focus on clinical effects of this combination in management of human ulcerative colitis. Further molecular and signaling pathway studies will help to understand the mechanisms involved in the treatment of colitis and inflammatory diseases. Copyright © 2016 Elsevier GmbH. All rights reserved.

  1. Types of Ulcerative Colitis

    Science.gov (United States)

    ... Colitis? > Types of Ulcerative Colitis Types of Ulcerative Colitis Email Print + Share If you are diagnosed with ... abdomen may occur in active disease. Left-sided Colitis Continuous inflammation that begins at the rectum and ...

  2. Diet-induced expansion of pathobionts in experimental colitis: Implications for tailored therapies

    OpenAIRE

    Devkota, Suzanne; Chang, Eugene B.

    2013-01-01

    Evidence presented in our recent study and elsewhere suggests that the interplay of dietary macronutrients with the intestinal lumen alters the microbial environment, and thus host-microbe interactions, in ways that are not always in a favorable, mutualistic fashion. Specifically, in inflammatory bowel diseases (IBD), experimental and clinical observations have implicated a detrimental impact of environmental/microbial factors on the etiopathogenesis of IBD in individuals with a background of...

  3. Curative effect of Terminalia chebula extract on acetic acid-induced experimental colitis: role of antioxidants, free radicals and acute inflammatory marker.

    Science.gov (United States)

    Gautam, M K; Goel, Shalini; Ghatule, R R; Singh, A; Nath, G; Goel, R K

    2013-10-01

    The present study has evaluated the healing effects of extract of dried fruit pulp of Terminalia chebula (TCE) on acetic acid (AA)-induced colitis in rats. TCE (600 mg/kg) showed healing effects against AA-induced colonic damage score and weight when administered orally daily for 14 days. TCE was further studied for its effects on various physical (mucus/blood in stool and stool frequency, food and water intake and body weight changes), histology, antibacterial activity and free radicals (NO and LPO), antioxidants (SOD, CAT and GSH) and myeloperoxidase in colonic tissue. Intra-colonic AA administration increased colonic mucosal damage and inflammation, mucus/bloody diarrhoea, stool frequency, but decreased body weight which were reversed by TCE and sulfasalazine (SS, positive control) treatments. TCE showed antibacterial activity and both TCE and SS enhanced the antioxidants, but decreased free radicals and myeloperoxidase activities affected in acetic acid-induced colitis. TCE indicated the presence of active principles with proven antioxidants, anti-inflammatory, immunomodulatory, and free radical scavenging and healing properties. Thus, TCE seemed to be safe and effective in healing experimental colitis.

  4. Ischemic Colitis

    Science.gov (United States)

    ... Leiden, may increase the risk of ischemic colitis. High cholesterol, which can lead to atherosclerosis. Reduced blood flow, due to heart failure, low blood pressure and shock. Previous abdominal surgery. Scar tissue that forms after surgery may cause ...

  5. Ischemic Colitis

    Science.gov (United States)

    ... supply blood to the colon are the superior mesenteric artery and the inferior mesenteric artery. Ischemic colitis occurs when blood flow to ... patterns of presentation, diagnosis, and management of colon ischemia (CI). American Journal of Gastroenterology. 2015;110:18. ...

  6. Microscopic colitis.

    Science.gov (United States)

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

    2012-11-21

    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-epithelial 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.

  7. Pseudomembranous Colitis

    OpenAIRE

    Farooq, Priya D.; Nathalie H. Urrunaga; Tang, Derek M.; von Rosenvinge, Erik C.

    2015-01-01

    Pseudomembranous colitis is an inflammatory condition of the colon characterized by elevated yellow-white plaques that coalesce to form pseudomembranes on the mucosa. Patients with the condition commonly present with abdominal pain, diarrhea, fever, and leukocytosis. Because pseudomembranous colitis is often associated with C. difficile infection, stool testing and empiric antibiotic treatment should be initiated when suspected. When results of C. difficile testing are negative and symptoms p...

  8. Suppression of NF-κB signaling and NLRP3 inflammasome activation in macrophages is responsible for the amelioration of experimental murine colitis by the natural compound fraxinellone

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Xue-Feng; Ouyang, Zi-Jun; Feng, Li-Li; Chen, Gong; Guo, Wen-Jie; Shen, Yan; Wu, Xu-Dong; Sun, Yang, E-mail: yangsun@nju.edu.cn; Xu, Qiang, E-mail: molpharm@163.com

    2014-11-15

    Inflammatory bowel disease (IBD) affects millions of people worldwide. Although the etiology of this disease is uncertain, accumulating evidence indicates a key role for the activated mucosal immune system. In the present study, we examined the effects of the natural compound fraxinellone on dextran sulfate sodium (DSS)-induced colitis in mice, an animal model that mimics IBD. Treatment with fraxinellone significantly reduced weight loss and diarrhea in mice and alleviated the macroscopic and microscopic signs of the disease. In addition, the activities of myeloperoxidase and alkaline phosphatase were markedly suppressed, while the levels of glutathione were increased in colitis tissues following fraxinellone treatment. This compound also decreased the colonic levels of interleukin (IL)-1β, IL-6, IL-18 and tumor necrosis factor (TNF)-α in a concentration-dependent manner. These effects of fraxinellone in mice with experimental colitis were attributed to its inhibition of CD11b{sup +} macrophage infiltration. The mRNA levels of macrophage-related molecules in the colon, including intercellular adhesion molecule 1 (ICAM1), vascular cell adhesion molecule 1 (VCAM1), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX2), were also markedly inhibited following fraxinellone treatment. The results from in vitro assays showed that fraxinellone significantly reduced lipopolysaccharide (LPS)-induced production of nitric oxide (NO), IL-1β and IL-18 as well as the activity of iNOS in both THP-1 cells and mouse primary peritoneal macrophages. The mechanisms responsible for these effects were attributed to the inhibitory role of fraxinellone in NF-κB signaling and NLRP3 inflammasome activation. Overall, our results support fraxinellone as a novel drug candidate in the treatment of colonic inflammation. - Highlights: • Fraxinellone, a lactone compound, alleviated DSS induced colitis. • The effects of fraxinellone were attributed to its inhibition on

  9. Diet-induced expansion of pathobionts in experimental colitis: implications for tailored therapies.

    Science.gov (United States)

    Devkota, Suzanne; Chang, Eugene B

    2013-01-01

    Evidence presented in our recent study and elsewhere suggests that the interplay of dietary macronutrients with the intestinal lumen alters the microbial environment, and thus host-microbe interactions, in ways that are not always in a favorable, mutualistic fashion. Specifically, in inflammatory bowel diseases (IBD), experimental and clinical observations have implicated a detrimental impact of environmental/microbial factors on the etiopathogenesis of IBD in individuals with a background of genetic susceptibility to the disease. Thus, now more than ever, we are realizing that specific intestinal microbes can metabolize and react to a wide array of dietary compositions that, in turn, markedly alter microbial populations. We aimed to understand if certain dietary fats that are prevalent in Western diets are capable of precipitating colonic inflammation through their actions on the enteric microbiota. On a background of genetic susceptibility, these microbial changes can impact host immune homeostasis and increase risk for disease. Here we elaborate on our findings and their potential implications for future medical care.

  10. Cilostazol and enzymatically modified isoquercitrin attenuate experimental colitis and colon cancer in mice by inhibiting cell proliferation and inflammation.

    Science.gov (United States)

    Kangawa, Yumi; Yoshida, Toshinori; Maruyama, Kiyoshi; Okamoto, Minako; Kihara, Tohru; Nakamura, Michi; Ochiai, Masako; Hippo, Yoshitaka; Hayashi, Shim-Mo; Shibutani, Makoto

    2017-02-01

    We previously reported the anti-inflammatory effects of cilostazol, a selective inhibitor of phosphodiesterase 3, and two antioxidants, enzymatically modified isoquercitrin and α-lipoic acid in a dextran sodium sulphate-induced colitis mouse model. We further examined the chemopreventive effects of these substances in a murine azoxymethane/dextran sodium sulphate -induced colorectal carcinoma model and compared the effects with those of the well-known anticancer natural plant pigment, anthocyanin. In addition, the effects on cell proliferation activity were evaluated in colon cancer cell lines and mucosal epithelial cells in a model of acute dextran sodium sulphate-induced colitis. Cilostazol and enzymatically modified isoquercitrin improved the outcome of azoxymethane/dextran sodium sulphate-induced colorectal cancer along with anthocyanin though inhibiting inflammation and cell proliferation, but the effect of α-lipoic acid was minimal. Inhibition of cell proliferation by cilostazol was confirmed in vitro. In the acute dextran sodium sulphate-induced colitis model, cilostazol and enzymatically modified isoquercitrin prevented the decrease in epithelial proliferative cells. These results indicate that cilostazol and enzymatically modified isoquercitrin first exhibited an anti-dextran sodium sulphate effect at the initial stage of colitis and then showed antitumour effects throughout subsequent inflammation-related cancer developmental stages. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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

  12. Expression of Ecto-nucleoside Triphosphate Diphosphohydrolases-2 and -3 in the Enteric Nervous System Affects Inflammation in Experimental Colitis and Crohn's Disease.

    Science.gov (United States)

    Feldbrügge, Linda; Moss, Alan C; Yee, Eric U; Csizmadia, Eva; Mitsuhashi, Shuji; Longhi, Maria Serena; Sandhu, Bynvant; Stephan, Holger; Wu, Yan; Cheifetz, Adam S; Müller, Christa E; Sévigny, Jean; Robson, Simon C; Jiang, Z Gordon

    2017-09-01

    Recent studies have suggested that the enteric nervous system can modulate gut immunity. Ecto-nucleoside triphosphate diphosphohydrolases [E-NTPDases] regulate purinergic signalling by sequential phosphohydrolysis of pro-inflammatory extracellular adenosine 5'-triphosphate [ATP]. Herein, we test the hypothesis that E-NTPDases modulate gut inflammation via neuro-immune crosstalk. We determined expression patterns of NTPDase2 and NTPDase3 in murine and human colon. Experimental colitis was induced by dextran sodium sulphate [DSS] in genetically engineered mice deficient in NTPDase2 or NTPDase3. We compared plasma adenosine diphosphatase [ADPase] activity from Crohn's patients and healthy controls, and linked the enzyme activity to Crohn's disease activity. NTPDase2 and -3 were chiefly expressed in cells of the enteric nervous system in both murine and human colon. When compared with wild type, DSS-induced colitis was exacerbated in Entpd2, and to a lesser extent, Entpd3 null mice as measured by disease activity score and histology, and marked anaemia was seen in both. Colonic macrophages isolated from Entpd2 null mice displayed a pro-inflammatory phenotype compared with wild type. In human plasma, Crohn's patients had decreases in ADPase activity when compared with healthy controls. The drop in ADPase activity was likely associated with changes in NTPDase2 and -3, as suggested by inhibitor studies, and were correlated with Crohn's disease activity. NTPDase2 and -3 are ecto-enzymes expressed in the enteric nervous system. Both enzymes confer protection against gut inflammation in experimental colitis and exhibit alterations in Crohn's disease. These observations suggest that purinergic signalling modulated by E-NTPDases governs neuro-immune interactions that are relevant in Crohn's disease.

  13. Specific Gene- and MicroRNA-Expression Pattern Contributes to the Epithelial to Mesenchymal Transition in a Rat Model of Experimental Colitis

    Directory of Open Access Journals (Sweden)

    Éva Boros

    2017-01-01

    Full Text Available The aim of this study was to determine the gene- and microRNA-expression profile contributing to epithelial to mesenchymal transition in a rat model of experimental colitis. For this, inflammation was induced by injecting 2,4,6-trinitrobenzene sulphonic acid to the colon of male Wistar rats. Samples were taken from both inflamed and uninflamed regions of the same colon, total RNA was isolated, and the mRNA and microRNA expressions were monitored. We have determined that the expression of genes responsible for inducing mesenchymal phenotype, such as Egr1, Fgf2, Fgf7, Jak2, Notch2, Hif1α, Zeb2, Mmp9, Lox, and Vim, was all significantly induced in the inflamed regions of the affected colons while the epithelial marker E-cadherin (Cdh1 was downregulated. In contrast, the expression of microRNAs miR-192, miR-143, miR-375, miR-30a, miR-107, and miR-200b responsible for the regulation of the above mentioned genes was significantly downregulated in inflamed colon. Importantly, we detected moderate induction in the expression of five out of six tested microRNAs in the uninflamed regions. In summary, we identified numerous interacting genes and microRNAs with mutually exclusive expression pattern in inflamed regions of colitis-induced rats. These findings suggest that—among others—an important step in the epithelial to mesenchymal transition in experimental colitis is the dysregulated microRNA expression.

  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. TH17 Cell Induction and Effects of IL-17A and IL-17F Blockade in Experimental Colitis

    DEFF Research Database (Denmark)

    Wedebye Schmidt, Esben Gjerløff; Larsen, Hjalte List; Kristensen, Nanna Ny

    2013-01-01

    T helper (TH) 17 cells are believed to play a pivotal role in development of inflammatory bowel disease, and their contribution to intestinal inflammation has been studied in various models of colitis. TH17 cells produce a range of cytokines, some of which are potential targets for immunotherapy........ However, blockade of IL-17A alone with secukinumab was not effective in Crohn's disease. In this regard, the pathogenic impact of IL-17A versus IL-17F during intestinal inflammation is still unresolved....

  16. Worm proteins of Schistosoma mansoni reduce the severity of experimental chronic colitis in mice by suppressing colonic proinflammatory immune responses.

    Directory of Open Access Journals (Sweden)

    Marthe Heylen

    Full Text Available Although helminthic therapy as a possible new option to treat inflammatory bowel disease is a well-established concept by now, the search for immunomodulatory helminth-derived compounds and their mechanisms of action is still ongoing. We investigated the therapeutic potential and the underlying immunological mechanisms of Schistosoma mansoni soluble worm proteins (SmSWP in an adoptive T cell transfer mouse model of chronic colitis. Both a curative and a preventive treatment protocol were included in this study. The curative administration of SmSWP (started when colitis was established, resulted in a significant improvement of the clinical disease score, colonoscopy, macroscopic and microscopic inflammation score, colon length and myeloperoxidase activity. The therapeutic potential of the preventive SmSWP treatment (started before colitis was established, was less pronounced compared with the curative SmSWP treatment but still resulted in an improved clinical disease score, body weight loss, colon length and microscopic inflammation score. Both the curative and preventive SmSWP treatment downregulated the mRNA expression of the proinflammatory cytokines IFN-γ and IL-17A and upregulated the mRNA expression of the anti-inflammatory cytokine IL-4 in the colon at the end of the experiment. This colonic immunomodulatory effect of SmSWP could not be confirmed at the protein level. Moreover, the effect of SmSWP appeared to be a local colonic phenomenon, since the flow cytometric T cell characterization of the mesenteric lymph nodes and the cytokine measurements in the serum did not reveal any effect of SmSWP treatment. In conclusion, SmSWP treatment reduced the severity of colitis in the adoptive transfer mouse model via the suppression of proinflammatory cytokines and the induction of an anti-inflammatory response in the colon.

  17. Worm Proteins of Schistosoma mansoni Reduce the Severity of Experimental Chronic Colitis in Mice by Suppressing Colonic Proinflammatory Immune Responses

    Science.gov (United States)

    Heylen, Marthe; Ruyssers, Nathalie E.; De Man, Joris G.; Timmermans, Jean-Pierre; Pelckmans, Paul A.; Moreels, Tom G.; De Winter, Benedicte Y.

    2014-01-01

    Although helminthic therapy as a possible new option to treat inflammatory bowel disease is a well-established concept by now, the search for immunomodulatory helminth-derived compounds and their mechanisms of action is still ongoing. We investigated the therapeutic potential and the underlying immunological mechanisms of Schistosoma mansoni soluble worm proteins (SmSWP) in an adoptive T cell transfer mouse model of chronic colitis. Both a curative and a preventive treatment protocol were included in this study. The curative administration of SmSWP (started when colitis was established), resulted in a significant improvement of the clinical disease score, colonoscopy, macroscopic and microscopic inflammation score, colon length and myeloperoxidase activity. The therapeutic potential of the preventive SmSWP treatment (started before colitis was established), was less pronounced compared with the curative SmSWP treatment but still resulted in an improved clinical disease score, body weight loss, colon length and microscopic inflammation score. Both the curative and preventive SmSWP treatment downregulated the mRNA expression of the proinflammatory cytokines IFN-γ and IL-17A and upregulated the mRNA expression of the anti-inflammatory cytokine IL-4 in the colon at the end of the experiment. This colonic immunomodulatory effect of SmSWP could not be confirmed at the protein level. Moreover, the effect of SmSWP appeared to be a local colonic phenomenon, since the flow cytometric T cell characterization of the mesenteric lymph nodes and the cytokine measurements in the serum did not reveal any effect of SmSWP treatment. In conclusion, SmSWP treatment reduced the severity of colitis in the adoptive transfer mouse model via the suppression of proinflammatory cytokines and the induction of an anti-inflammatory response in the colon. PMID:25313594

  18. Peroxisome Proliferator-activated Receptor-γ Coactivator 1-α (PGC1α) Protects against Experimental Murine Colitis*

    Science.gov (United States)

    Cunningham, Kellie E.; Vincent, Garret; Sodhi, Chhinder P.; Novak, Elizabeth A.; Ranganathan, Sarangarajan; Egan, Charlotte E.; Stolz, Donna Beer; Rogers, Matthew B.; Firek, Brian; Morowitz, Michael J.; Gittes, George K.; Zuckerbraun, Brian S.; Hackam, David J.; Mollen, Kevin P.

    2016-01-01

    Peroxisome proliferator-activated receptor-γ coactivator 1-α (PGC1α) is the primary regulator of mitochondrial biogenesis and was recently found to be highly expressed within the intestinal epithelium. PGC1α is decreased in the intestinal epithelium of patients with inflammatory bowel disease, but its role in pathogenesis is uncertain. We now hypothesize that PGC1α protects against the development of colitis and helps to maintain the integrity of the intestinal barrier. We selectively deleted PGC1α from the intestinal epithelium of mice by breeding a PGC1αloxP/loxP mouse with a villin-cre mouse. Their progeny (PGC1αΔIEC mice) were subjected to 2% dextran sodium sulfate (DSS) colitis for 7 days. The SIRT1 agonist SRT1720 was used to enhance PGC1α activation in wild-type mice during DSS exposure. Mice lacking PGC1α within the intestinal epithelium were more susceptible to DSS colitis than their wild-type littermates. Pharmacologic activation of PGC1α successfully ameliorated disease and restored mitochondrial integrity. These findings suggest that a depletion of PGC1α in the intestinal epithelium contributes to inflammatory changes through a failure of mitochondrial structure and function as well as a breakdown of the intestinal barrier, which leads to increased bacterial translocation. PGC1α induction helps to maintain mitochondrial integrity, enhance intestinal barrier function, and decrease inflammation. PMID:26969166

  19. 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.

  20. Ulcerative colitis

    Science.gov (United States)

    ... are lactose intolerant. Dairy products are a good source of protein and calcium. STRESS You may feel worried, embarrassed, or even sad ... Groups Social support can often help ... the best treatment and coping with the condition. The Crohn's and Colitis Foundation ...

  1. 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...

  2. Altered colonic mucosal Polyunsaturated Fatty Acid (PUFA derived lipid mediators in ulcerative colitis: new insight into relationship with disease activity and pathophysiology.

    Directory of Open Access Journals (Sweden)

    Mojgan Masoodi

    Full Text Available Ulcerative colitis (UC is a relapsing inflammatory disorder of unconfirmed aetiology, variable severity and clinical course, characterised by progressive histological inflammation and with elevation of eicosanoids which have a known pathophysiological role in inflammation. Therapeutic interventions targetting eicosanoids (5-aminosalicylates (ASA are effective first line and adjunctive treatments in mild-moderate UC for achieving and sustaining clinical remission. However, the variable clinical response to 5-ASA and frequent deterioration in response to cyclo-oxygenase (COX inhibitors, has prompted an in depth simultaneous evaluation of multiple lipid mediators (including eicosanoids within the inflammatory milieu in UC. We hypothesised that severity of inflammation is associated with alteration of lipid mediators, in relapsing UC.Study was case-control design. Mucosal lipid mediators were determined by LC-MS/MS lipidomics analysis on mucosal biopsies taken from patients attending outpatients with relapsing UC. Univariate and multivariate statistical analyses were used to investigate the association of mucosal lipid mediators, with the disease state and severity graded histologically.Levels of PGE2, PGD2, TXB2, 5-HETE, 11-HETE, 12-HETE and 15-HETE are significantly elevated in inflamed mucosa and correlate with severity of inflammation, determined using validated histological scoring systems.Our approach of capturing inflammatory mediator signature at different stages of UC by combining comprehensive lipidomics analysis and computational modelling could be used to classify and predict mild-moderate inflammation; however, predictive index is diminished in severe inflammation. This new technical approach could be developed to tailor drug treatments to patients with active UC, based on the mucosal lipid mediator profile.

  3. Adipose-Derived Stem Cells Ameliorate Experimental Murine Colitis via TSP-1-Dependent Activation of Latent TGF-β.

    Science.gov (United States)

    Takeyama, Hiroshi; Mizushima, Tsunekazu; Uemura, Mamoru; Haraguchi, Naotsugu; Nishimura, Junichi; Hata, Taishi; Matsuda, Chu; Takemasa, Ichiro; Ikenaga, Masakazu; Murata, Kohei; Yamamoto, Hirofumi; Doki, Yuichiro; Mori, Masaki

    2017-08-01

    Adipose tissue-derived stem cells (ASCs) have been investigated as therapeutic tools for a variety of autoimmune diseases, including inflammatory diseases. However, the mechanisms underlying the immunomodulatory properties of ASCs are not well understood. Here, we investigated the mechanism of regulatory T cell (Treg) induction in ASC therapy in a murine model of inflammatory bowel disease. Acute colitis was induced in mice using dextran sulfate sodium and ASCs administered intraperitoneally. Tregs and CD103+ dendritic cells were analyzed in the mesenteric lymph nodes (MLNs), spleen, and colonic lamina propria (CLP). Activation of latent TGF-β by ASCs was analyzed in vitro using ELISA. siRNA technology was used to create ASCs in which TSP-1 or integrinαv was knocked down in order to investigate the involvement of these proteins in the activation of latent TGF-β. In addition, TSP-1-knockdown ASCs were administered to mice with colitis to assess their clinical efficacy in vivo. Systemic administration of ASCs significantly lessened the clinical and histopathological severity of colitis. ASCs were distributed throughout the lymphatic system in the MLNs and spleen. Tregs were increased in the MLNs and CLP, but CD103+ dendritic cells were not significantly altered. The ASCs activated latent TGF-β. TSP-1 knockdown impaired TGF-β activation in vitro and abrogated the therapeutic effects of the ASCs in vivo. Furthermore, Tregs were not increased in the MLNs and CLP from mice treated with TSP-1-knockdown ASCs. These results demonstrate that ASCs induce Tregs by activating latent TGF-β via TSP-1, independent of CD103+ dendritic cell induction.

  4. Rivastigmine alleviates experimentally induced colitis in mice and rats by acting at central and peripheral sites to modulate immune responses.

    Directory of Open Access Journals (Sweden)

    Helena Shifrin

    Full Text Available The cholinergic anti-inflammatory system and α7 nicotinic receptors in macrophages have been proposed to play a role in neuroimmunomodulation and in the etiology of ulcerative colitis. We investigated the ability of a cholinesterase (ChE inhibitor rivastigmine, to improve the pathology of ulcerative colitis by increasing the concentration of extracellular acetylcholine in the brain and periphery. In combination with carbachol (10 µM, rivastigmine (1 µM significantly decreased the release of nitric oxide, TNF-α, IL-1β and IL-6 from lipopolysaccharide-activated RAW 264.7 macrophages and this effect was abolished by α7 nicotinic receptor blockade by bungarotoxin. Rivastigmine (1 mg/kg but not (0.5 mg/kg, injected subcutaneously once daily in BALB/c mice with colitis induced by 4% dextran sodium sulphate (DSS, reduced the disease activity index (DAI by 60% and damage to colon structure. Rivastigmine (1 mg/kg also reduced myeloperoxidase activity and IL-6 by >60%, and the infiltration of CD11b expressing cells by 80%. These effects were accompanied by significantly greater ChE inhibition in cortex, brain stem, plasma and colon than that after 0.5 mg/kg. Co-administration of rivastigmine (1 mg/kg with the muscarinic antagonist scopolamine significantly increased the number of CD11b expressing cells in the colon but did not change DAI compared to those treated with rivastigmine alone. Rivastigmine 1 and 2 mg given rectally to rats with colitis induced by rectal administration of 30 mg dintrobezene sulfonic acid (DNBS also caused a dose related reduction in ChE activity in blood and colon, the number of ulcers and area of ulceration, levels of TNF-α and in MPO activity. The study revealed that the ChE inhibitor rivastigmine is able to reduce gastro-intestinal inflammation by actions at various sites at which it preserves ACh. These include ACh released from vagal nerve endings that activates alpha7 nicotinic receptors on circulating macrophages

  5. Rivastigmine alleviates experimentally induced colitis in mice and rats by acting at central and peripheral sites to modulate immune responses.

    Science.gov (United States)

    Shifrin, Helena; Nadler-Milbauer, Mirela; Shoham, Shai; Weinstock, Marta

    2013-01-01

    The cholinergic anti-inflammatory system and α7 nicotinic receptors in macrophages have been proposed to play a role in neuroimmunomodulation and in the etiology of ulcerative colitis. We investigated the ability of a cholinesterase (ChE) inhibitor rivastigmine, to improve the pathology of ulcerative colitis by increasing the concentration of extracellular acetylcholine in the brain and periphery. In combination with carbachol (10 µM), rivastigmine (1 µM) significantly decreased the release of nitric oxide, TNF-α, IL-1β and IL-6 from lipopolysaccharide-activated RAW 264.7 macrophages and this effect was abolished by α7 nicotinic receptor blockade by bungarotoxin. Rivastigmine (1 mg/kg) but not (0.5 mg/kg), injected subcutaneously once daily in BALB/c mice with colitis induced by 4% dextran sodium sulphate (DSS), reduced the disease activity index (DAI) by 60% and damage to colon structure. Rivastigmine (1 mg/kg) also reduced myeloperoxidase activity and IL-6 by >60%, and the infiltration of CD11b expressing cells by 80%. These effects were accompanied by significantly greater ChE inhibition in cortex, brain stem, plasma and colon than that after 0.5 mg/kg. Co-administration of rivastigmine (1 mg/kg) with the muscarinic antagonist scopolamine significantly increased the number of CD11b expressing cells in the colon but did not change DAI compared to those treated with rivastigmine alone. Rivastigmine 1 and 2 mg given rectally to rats with colitis induced by rectal administration of 30 mg dintrobezene sulfonic acid (DNBS) also caused a dose related reduction in ChE activity in blood and colon, the number of ulcers and area of ulceration, levels of TNF-α and in MPO activity. The study revealed that the ChE inhibitor rivastigmine is able to reduce gastro-intestinal inflammation by actions at various sites at which it preserves ACh. These include ACh released from vagal nerve endings that activates alpha7 nicotinic receptors on circulating macrophages and in

  6. 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 ...

  7. Huaier aqueous extract protects against dextran sulfate sodium-induced experimental colitis in mice by inhibiting NLRP3 inflammasome activation.

    Science.gov (United States)

    Wang, Lijuan; Yu, Zhongxia; Wei, Chao; Zhang, Li; Song, Hui; Chen, Bing; Yang, Qifeng

    2017-05-16

    The use of Trametes robiniophila Murr. (Huaier) as a complementary therapy for cancer has recently become increasingly common in China. However, whether Huaier can regulate host immune responses, especially innate immunity, remains largely unknown. The NLRP3 inflammasome is a multimeric complex consisting of NLRP3, ASC and caspase-1. NLRP3 inflammasomes respond to a variety of endogenous (damage-associated molecular patterns) and exogenous (pathogen-associated molecular patterns) stimuli, and play crucial roles in host defense against pathogens and multiple diseases such as ulcerative colitis (UC). In this study, we investigated the anti-inflammatory effect of Huaier in dextran sulfate sodium (DSS)-induced murine colitis and revealed the underlying mechanisms by targeting NLRP3 inflammasomes. In C57BL/6 mice, oral administration of Huaier attenuated DSS-induced colon shortening and colonic pathological damage. Furthermore, we analyzed the effect of Huaier on NLRP3 inflammasome activation in macrophages. Huaier inhibited NLRP3 inflammasome activation-induced IL-1β secretion and caspase-1 cleavage. Moreover, Huaier decreased NLRP3 protein expression via promoting NLRP3 degradation through the autophagy lysosome pathway. Therefore, our findings demonstrate a novel function for Huaier in the regulation of NLRP3 inflammasome activation and suggest a potential role for Huaier in NLRP3 inflammasome-associated diseases.

  8. CSA13 inhibits colitis-associated intestinal fibrosis via a formyl peptide receptor like-1 mediated HMG-CoA reductase pathway.

    Science.gov (United States)

    Xu, Chunlan; Ghali, Sally; Wang, Jiani; Shih, David Q; Ortiz, Christina; Mussatto, Caroline C; Lee, Elaine C; Tran, Diana H; Jacobs, Jonathan P; Lagishetty, Venu; Fleshner, Phillip; Robbins, Lori; Vu, Michelle; Hing, Tressia C; McGovern, Dermot P B; Koon, Hon Wai

    2017-11-27

    Many Crohn's disease (CD) patients develop intestinal strictures, which are difficult to prevent and treat. Cationic steroid antimicrobial 13 (CSA13) shares cationic nature and antimicrobial function with antimicrobial peptide cathelicidin. As many functions of cathelicidin are mediated through formyl peptide receptor-like 1 (FPRL1), we hypothesize that CSA13 mediates anti-fibrogenic effects via FPRL1. Human intestinal biopsies were used in clinical data analysis. Chronic trinitrobenzene sulfonic acid (TNBS) colitis-associated intestinal fibrosis mouse model with the administration of CSA13 was used. Colonic FPRL1 mRNA expression was positively correlated with the histology scores of inflammatory bowel disease patients. In CD patients, colonic FPRL1 mRNA was positively correlated with intestinal stricture. CSA13 administration ameliorated intestinal fibrosis without influencing intestinal microbiota. Inhibition of FPRL1, but not suppression of intestinal microbiota, reversed these protective effects of CSA13. Metabolomic analysis indicated increased fecal mevalonate levels in the TNBS-treated mice, which were reduced by the CSA13 administration. CSA13 inhibited colonic HMG-CoA reductase activity in an FPRL1-dependent manner. Mevalonate reversed the anti-fibrogenic effect of CSA13. The increased colonic FPRL1 expression is associated with severe mucosal disease activity and intestinal stricture. CSA13 inhibits intestinal fibrosis via FPRL1-dependent modulation of HMG-CoA reductase pathway.

  9. Pseudomembranous colitis complicating ulcerative colitis.

    Science.gov (United States)

    Kawaratani, Hideto; Tsujimoto, Tatsuhiro; Toyohara, Masahisa; Kin, Kenichi; Taniguchi, Tomoyasu; Shirai, Yasuyo; Ikenaka, Yasuhide; Nakayama, Masaki; Fujii, Hisao; Fukui, Hiroshi

    2010-10-01

    Clostridium difficile toxin (CD toxin) causes antibiotic-associated colitis, or pseudomembranous colitis (PMC). Although CD toxin is sometimes found in the stools of patients with ulcerative colitis (UC), UC is rarely complicated by PMC. We report herein a case of PMC complicating UC, and present a review of the literature. A 71-year-old woman was diagnosed as having UC of the left colon, and treated with prednisolone and mesalazine. Later, however, lumbar spinal stenosis was also detected. After surgery for lumbar spinal stenosis, she suffered postoperative infection of the lumbar region. After 3-week treatment with antibiotics, she developed diarrhea, bloody stools, and abdominal pain. Colonoscopy revealed PMC of the cecum, ascending colon, sigmoid colon, and rectum. Stools were positive for CD toxin. As cefotiam hydrochloride, levofloxacin hydrate (LVFX), and prednisolone were suspected as the causative agents, she was treated with 1.5 g vancomycin (VCM) daily for 2 weeks without ceasing LVFX. Her symptoms improved, and colonoscopy confirmed resolution of PMC. The possibility of PMC should be considered in UC patients treated with antibiotics, immunosuppressive agents or corticosteroids who complain of gastrointestinal symptoms. These patients should be thoroughly investigated by several modalities, including colonoscopy and CD toxin testing. © 2010 The Authors. Digestive Endoscopy © 2010 Japan Gastroenterological Endoscopy Society.

  10. Lactobacillus kefiranofaciens M1 isolated from milk kefir grains ameliorates experimental colitis in vitro and in vivo.

    Science.gov (United States)

    Chen, Y P; Hsiao, P J; Hong, W S; Dai, T Y; Chen, M J

    2012-01-01

    Lactobacillus kefiranofaciens M1, isolated from and identified in Taiwanese milk kefir grain, has demonstrated immune-modulating activity. In the present study, we further investigated the effects of Lb. kefiranofaciens M1 on intestinal epithelial cells in vitro and on dextran sodium sulfate (DSS)-induced colitis in vivo. The possible mechanisms regarding the cytokine products and intestinal epithelial barrier restoration as well as the putative receptor for the protective effects of Lb. kefiranofaciens M1 were investigated. In vitro results indicated that Lb. kefiranofaciens M1 could strengthen the epithelial barrier function in vitro by increasing the transepithelial electrical resistance (TEER) and significantly upregulated the level of the chemokine CCL-20 at both the apical and basolateral sites. The in vivo effects of Lb. kefiranofaciens M1 on the regulation of intestinal physiology indicate that this strain could ameliorate DSS-induced colitis with a significant attenuation of the bleeding score and colon length shortening. Production of proinflammatory cytokines was decreased and that of the antiinflammatory cytokine IL-10 was increased in the DSS-treated mice given Lb. kefiranofaciens M1. The putative receptor for the protective effects of Lb. kefiranofaciens M1 was toll-like receptor 2 (TLR2), which was involved in probiotic-induced cytokine production in vitro and in attenuation of the bleeding score and colon length shortening in vivo. In this study, the kefir lactobacillus Lb. kefiranofaciens M1 clearly demonstrated an anticolitis effect. Based on these results, Lb. kefiranofaciens M1 has the potential to be applied in fermented dairy products as an alternative therapy for intestinal disorders. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  11. Maternal and neonatal dietary intake of balanced n-6/n-3 fatty acids modulates experimental colitis in young adult rats.

    Science.gov (United States)

    Reddy, K Vijay Kumar; Naidu, K Akhilender

    2016-08-01

    The imbalance of n-6 and n-3 polyunsaturated fatty acids in the maternal diet impairs intestinal barrier development and sensitizes the colon response to inflammatory insults in the young rats. With a view to overcoming this issue, we designed this study to investigate the effect of maternal and neonatal intake of different proportions of n-6/n-3 fatty acids on colon inflammation in the young adult rats. Female Wistar rats were assigned into four groups, and each group fed one of four semisynthetic diets, namely n-6, low n-3, n-6/n-3 and n-3 fatty acids for 8 weeks prior to mating, during gestation and lactation periods. At weaning, the pups were separated from the dams and fed diet similar to the mothers. Colitis was induced on postnatal day 35, by administering 2 % dextran sulfate sodium in drinking water for 10 days. Colitis was assessed based on the clinical and inflammatory markers in the colon. Fatty acid analysis was done in liver, RBC, colon and spleen. A balanced n-6/n-3 PUFA diet significantly improved the body weight loss, rectal bleeding and mortality in rats. This was associated with lower myeloperoxidase activity, nitric oxide, prostaglandin E2, TNF-α and IL-6, IL-8, COX-2 and iNOS levels in the colon tissues. Fatty acid analysis has shown that the arachidonic acid/docosahexaenoic acid ratio was significantly lower in liver, RBC, colon and spleen in n-6/n-3 and n-3 diet groups. We demonstrate that balanced n-6/n-3 PUFA supplementation in maternal and neonatal diet alters systemic AA/DHA ratio and attenuates colon inflammation in the young adult rats.

  12. Omega 3 fatty acids supplementation has an ameliorative effect in experimental ulcerative colitis despite increased colonic neutrophil infiltration Los suplementos de ácidos grasos omega 3 tienen efectos beneficiosos en colitis ulcerosa a pesar del aumento de la infiltracción por neutrófilos del colon

    Directory of Open Access Journals (Sweden)

    Ioannis Varnalidis

    2011-10-01

    Full Text Available Purpose: omega 3 polyunsaturated fatty acids have anti-inflammatory properties and can be beneficial in the treatment of inflammatory diseases, such as ulcerative colitis. Dextran sodium sulphate (DSS colitis in rats appears to mimic nearly all of the morphological characteristics and lesion distributions of ulcerative colitis. The purpose of the current study was to investigate the efficacy of omega 3 fatty acids in the treatment of experimental ulcerative colitis. Methods: thirty-six Wistar rats were randomly assigned to group A or group B receiving 5% dextran sulfate sodium (DSS in their drinking water for eight days. For the next eight days post-DSS, group A animals received tap-water, and group B animals were fed a nutritional solution containing high levels of omega 3 polyunsaturated fatty acids (ProSure®, Abbott Laboratories, Zwolle, Netherlands once per day, administrated with a orogastric feeding tube. Results: animals fed an omega 3 rich diet exhibited a statistically significant increase in hematocrit and hemoglobin levels, compared to animals drinking tap water, and a trend towards histopathological and clinical improvement, with the administration of omega 3 fatty acids ameliorating epithelial erosion by day 8 post-DSS, but no statistically significant difference was observed between group A and group B animals at 4 or 8 days post-DSS. Also, a statistically significant increase in neutrophil infiltration was observed, as depicted by myelohyperoxidase activity. Conclusion: our findings support a positive role of omega 3 polyunsaturated fatty acids supplementation in an experimental model of ulcerative colitis despite the increased colonic neutrophil infiltration. Further studies are needed in order to investigate the role of increased neutrophils in colonic mucosa.

  13. Importance of mast cell Prss31/transmembrane tryptase/tryptase-γ in lung function and experimental chronic obstructive pulmonary disease and colitis.

    Science.gov (United States)

    Hansbro, Philip M; Hamilton, Matthew J; Fricker, Michael; Gellatly, Shaan L; Jarnicki, Andrew G; Zheng, Dominick; Frei, Sandra M; Wong, G William; Hamadi, Sahar; Zhou, Saijun; Foster, Paul S; Krilis, Steven A; Stevens, Richard L

    2014-06-27

    Protease serine member S31 (Prss31)/transmembrane tryptase/tryptase-γ is a mast cell (MC)-restricted protease of unknown function that is retained on the outer leaflet of the plasma membrane when MCs are activated. We determined the nucleotide sequences of the Prss31 gene in different mouse strains and then used a Cre/loxP homologous recombination approach to create a novel Prss31(-/-) C57BL/6 mouse line. The resulting animals exhibited no obvious developmental abnormality, contained normal numbers of granulated MCs in their tissues, and did not compensate for their loss of the membrane tryptase by increasing their expression of other granule proteases. When Prss31-null MCs were activated with a calcium ionophore or by their high affinity IgE receptors, they degranulated in a pattern similar to that of WT MCs. Prss31-null mice had increased baseline airway reactivity to methacholine but markedly reduced experimental chronic obstructive pulmonary disease and colitis, thereby indicating both beneficial and adverse functional roles for the tryptase. In a cigarette smoke-induced model of chronic obstructive pulmonary disease, WT mice had more pulmonary macrophages, higher histopathology scores, and more fibrosis in their small airways than similarly treated Prss31-null mice. In a dextran sodium sulfate-induced acute colitis model, WT mice lost more weight, had higher histopathology scores, and contained more Cxcl-2 and IL-6 mRNA in their colons than similarly treated Prss31-null mice. The accumulated data raise the possibility that inhibitors of this membrane tryptase may provide additional therapeutic benefit in the treatment of humans with these MC-dependent inflammatory diseases. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. 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.

    Science.gov (United States)

    Park, Dong Ki; Park, Hye-Jin

    2013-01-01

    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.

  15. Effect of royal jelly on experimental colitis Induced by acetic acid and alteration of mast cell distribution in the colon of rats.

    Science.gov (United States)

    Karaca, T; Bayiroglu, F; Yoruk, M; Kaya, M S; Uslu, S; Comba, B; Mis, L

    2010-10-21

    This study investigated the effects of royal jelly (RJ) on acetic acid-induced colitis in rats. Twenty adult female Wistar albino rats were divided into four treatment groups of 5 animals each, including a control group (Group I); Group II was treated orally with RJ (150 mg kg(-1) body weight); Group III had acetic acid-induced colitis; and Group IV had acetic acid-induced colitis treated orally with RJ (150 mg kg(-1) body weight) for 4 weeks. Colitis was induced by intracolonic instillation of 4% acetic acid; the control group received physiological saline (10 mL kg(-1)). Colon samples were obtained under deep anaesthesia from animals in all groups. Tissues were fixed in 10% formalin neutral buffer solution for 24 h and embedded in paraffin. Six-micrometre-thick sections were stained with Mallory’s triple stain and toluidine blue in 1% aqueous solution at pH 1.0 for 5 min (for Mast Cells). RJ was shown to protect the colonic mucosa against the injurious effect of acetic acid. Colitis (colonic damage) was confirmed histomorphometrically as significant increases in the number of mast cells (MC) and colonic erosions in rats with acetic acid-induced colitis. The RJ treatment significantly decreased the number of MC and reduced the area of colonic erosion in the colon of RJ-treated rats compared with rats with untreated colitis. The results suggest that oral treatment with RJ could be used to treat colitis.

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

    Directory of Open Access Journals (Sweden)

    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

  17. 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....

  18. Effects of obesity on severity of colitis and cytokine expression in mouse mesenteric fat. Potential role of adiponectin receptor 1

    Science.gov (United States)

    Sideri, Aristea; Stavrakis, Dimitris; Bowe, Collin; Shih, David Q.; Fleshner, Phillip; Arsenescu, Violeta; Arsenescu, Razvan; Turner, Jerrold R.; Pothoulakis, Charalabos

    2015-01-01

    In inflammatory bowel disease (IBD), obesity is associated with worsening of the course of disease. Here, we examined the role of obesity in the development of colitis and studied mesenteric fat-epithelial cell interactions in patients with IBD. We combined the diet-induce obesity with the trinitrobenzene sulfonic acid (TNBS) colitis mouse model to create groups with obesity, colitis, and their combination. Changes in the mesenteric fat and intestine were assessed by histology, myeloperoxidase assay, and cytokine mRNA expression by real-time PCR. Medium from human mesenteric fat and cultured preadipocytes was obtained from obese patients and those with IBD. Histological analysis showed inflammatory cell infiltrate and increased histological damage in the intestine and mesenteric fat of obese mice with colitis compared with all other groups. Obesity also increased the expression of proinflammatory cytokines including IL-1β, TNF-α, monocyte chemoattractant protein 1, and keratinocyte-derived chemokine, while it decreased the TNBS-induced increases in IL-2 and IFN-γ in mesenteric adipose and intestinal tissues. Human mesenteric fat isolated from obese patients and those with and IBD demonstrated differential release of adipokines and growth factors compared with controls. Fat-conditioned media reduced adiponectin receptor 1 (AdipoR1) expression in human NCM460 colonic epithelial cells. AdipoR1 intracolonic silencing in mice exacerbated TNBS-induced colitis. In conclusion, obesity worsens the outcome of experimental colitis, and obesity- and IBD-associated changes in adipose tissue promote differential mediator release in mesenteric fat that modulates colonocyte responses and may affect the course of colitis. Our results also suggest an important role for AdipoR1 for the fat-intestinal axis in the regulation of inflammation during colitis. PMID:25591865

  19. 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

  20. Ulcerative Colitis - Multiple Languages

    Science.gov (United States)

    ... Expand Section Ulcerative Colitis: MedlinePlus Health Topic - English Colitis ulcerativa: Tema de salud de MedlinePlus - español (Spanish) National Library of Medicine Ulcerative Colitis - español (Spanish) Bilingual PDF Health Information Translations Ukrainian ( ...

  1. [Microscopic colitis: update 2014].

    Science.gov (United States)

    Burgmann, Konstantin; Fraga, Montserrat; Schoepfer, Alain M; Yun, Pu

    2014-09-03

    Microscopic colitis, which includes lymphocytic colitis and collagenous colitis, represents a frequent cause of chronic watery diarrhea especially in the elderly population. Several medications, such as nonsteroidal antiinflammatory drugs, proton pump inhibitors or antidepressants, as well as cigarette smoking have been recognized as risk factors for microscopic colitis. The diagnosis of microscopic colitis is based on a macroscopically normal ileo-colonoscopy and several biopsies from the entire colon, which demonstrate the pathognomonic histopathologic findings. Therapy is mainly based on the use of budesonide. Other medications, such as mesalazine, cholestyramine and bismuth, have been evaluated as well but the evidence is less solid.

  2. Effects of budesonide and probiotics enemas on the colonic mucosa of rats with experimental colitis Efeito de enemas contendo budesonida e probióticos na mucosa colonica de ratos com colite experimental

    Directory of Open Access Journals (Sweden)

    Mardem Machado de Souza

    2007-02-01

    Full Text Available PURPOSE: To investigate the effect of enemas containing probiotics and budesonide on the colonic mucosa in experimental colitis. METHODS: Fifty male Wistar rats with experimental colitis induced by 10% acetic acid enema were randomized to five groups (10 rats each according to the treatment: group 1 - saline solution, group 2 - budesonide (0.75 mg/kg/day, group 3 - probiotics (1mg/day, group 4 - probiotics plus budesonide, and group 5 - control, with not-treated rats. The following variables were studied: body weight, macroscopic and microscopic score of the colonic mucosa, and DNA content of the mucosa. RESULTS: All animals lost weight between the beginning and the end of the experiment (280+ 16 mg versus 249+21 mg, pOBJETIVO: Investigar o efeito da administração retal de probióticos e budesonida na mucosa colônica de ratos com colite experimental. MÉTODOS: Cinquenta ratos Wistar com colite experimental induzida pelo ácido acético à 10% foram randomizados em 5 grupos (n=10 por grupo para diferentes tratamentos: grupo 1 - solução fisiológica; grupo 2 - budesonida (0,75mg/kg/dia; grupo 3 - probióticos (1 g/dia; grupo 4 - probióticos associados a budesonida; e finalmente grupo 5 - controle, composto por ratos sem tratamento. As seguintes variáveis foram estudadas: peso corporal, aspecto macroscópico e microscópico da mucosa e conteúdo de DNA da mucosa colônica. RESULTADOS: Todos os animais perderam peso entre o início e o fim do experimento (280±16 vs 249±21g; p<0.001. Não houve diferença estatística significativa entre os grupos em relação a macroscopia e histologia. O grupo budesonida + probiótico apresentou conteúdo de DNA maior que o grupo controle (1,24±0,15 versus 0,92±0,30 g/100g de tecido; p=0,01. CONCLUSÃO: A associação de budesonida com probióticos acelera o trofismo mucoso na colite experimental.

  3. Effects of budesonide and probiotics enemas on the systemic inflammatory response of rats with experimental colitis Efeito de enemas contendo budesonida e probióticos na resposta inflamatória sistêmica de ratos com colite experimental

    Directory of Open Access Journals (Sweden)

    Mardem Machado de Souza

    2007-01-01

    Full Text Available PURPOSE: The aim of this study was to investigate the effect of enemas containing probiotics and budesonide on the systemic inflammatory response in experimental colitis. METHODS: Fifty male Wistar rats with experimental colitis induced by 10% acetic acid enema were randomized to five groups (10 rats each according to the treatment: group 1 - saline solution, group 2 - budesonide (0.75 mg/kg/day, group 3 - probiotics (1mg/day, group 4 - probiotics plus budesonide, and group 5 - control, with not-treated rats. The following variables were studied: body weight, serum levels of albumin, C-reactive protein and interleucine-6 (IL-6. RESULTS: All animals lost weight between the beginning and the end of the experiment (280+ 16 mg versus 249+21 mg, p0.05. Only probiotic rats presented a significant decrease of IL-6 than controls (0,30±0,08 mg/dL vs. 0,19±0,03 mg/dL; pOBJETIVO: Investigar o efeito da administração retal de probióticos e budesonida na resposta inflamatória de ratos com colite experimental. MÉTODOS: Cinqüenta ratos Wistar com colite experimental induzida pelo acido acético à 10% foram randomizados em 5 grupos (n=10 por grupo para diferentes tratamentos: grupo 1 - solução fisiológica; grupo 2 budesonida (0,75mg/kg/dia; grupo 3 - probióticos (1 g/dia; grupo 4 - probióticos associados a budesonida; e finalmente grupo 5 - controle, composto por ratos sem tratamento. As seguintes variáveis foram estudadas: peso corporal, dosagens séricas de albumina, proteína C reativa (PCR e interleucina-6 (IL-6. RESULTADOS: Todos os animais perderam peso entre o inicio e o fim do experimento (280±16 vs 249±21g; p0.05. As comparações entre o grupo controle (0,30±0,08 mg/dL e outros mostraram que houve uma queda significante nos níveis de IL-6 apenas no grupo probiótico (0,19±0,03 mg/dL; p<0.01. CONCLUSÃO: Probióticos são efetivos na diminuição do estado inflamatório mediado pela IL-6 na colite experimental.

  4. Right dorsal colitis.

    Science.gov (United States)

    Karcher, L F; Dill, S G; Anderson, W I; King, J M

    1990-01-01

    Moderate to severe ulcerative colitis of the right dorsal colon was diagnosed by necropsy or by exploratory celiotomy and biopsy in 13 horses with a primary clinical complaint of either colic, diarrhea, or weight loss. Clinical signs varied from acute fulminating diarrhea (possibly with fever), colic, dehydration, endotoxic shock and death, to a chronic condition manifested by mild intermittent colic up to several months in duration, and weight loss with or without mild diarrhea. In a large percentage of the horses, those affected had been hypovolemic and received nonsteroidal anti-inflammatory drugs (NSAID) or had received inappropriately high doses of phenylbutazone before the onset of illness. Experimental treatment of two horses with high doses of a phenylbutazone oral paste preparation (6 gm once daily for 5 days) and limitation of their water intake to approximately one half of maintenance requirement (for 5 days) resulted in reproduction of ulcerative colitis involving only the right dorsal colon, which was apparent at necropsy examination 11 and 15 days after initiation of drug use. It was concluded that localized ulcerative lesions in the right dorsal colon may be a previously unreported manifestation of toxicity due to the administration of NSAID.

  5. Microscopic colitis: a review.

    Science.gov (United States)

    Farrukh, A; Mayberry, J F

    2014-12-01

    In recent years, microscopic colitis has been increasingly diagnosed. This review was carried out to evaluate demographic factors for microscopic colitis and to perform a systematic assessment of available treatment options. Relevant publications up to December 2013 were identified following searches of PubMed and Google Scholar using the key words 'microscopic colitis', 'collagenous colitis' and 'lymphocytic colitis'. Two-hundred and forty-eight articles were identified. The term microscopic colitis includes lymphocytic colitis and collagenous colitis. Both have common clinical symptoms but are well defined histopathologically. The clinical course is usually benign, but serious complications, including death, may occur. A peak incidence from 60 to 70 years of age with a female preponderance is observed. Although most cases are idiopathic, associations with autoimmune disorders, such as coeliac disease and hypothyroidism, as well as with exposure to nonsteroidal anti-inflammatory drugs and proton-pump inhibitors, have been observed. The incidence and prevalence of microscopic colitis is rising and good-quality epidemiological research is needed. Treatment is currently largely based on anecdotal evidence and on results from limited clinical trials of budesonide. Long-term follow-up of these patients is not well established. The review synthesizes work on the definition of microscopic colitis and the relationship between collagenous and lymphocytic colitis. It reviews the international epidemiology and work on aetiology. In addition, it critically considers the efficacy of a range of treatments. Colorectal Disease © 2014 The Association of Coloproctology of Great Britain and Ireland.

  6. Is "ischemic" colitis ischemic?

    Science.gov (United States)

    Carlson, Ryan M; Madoff, Robert D

    2011-03-01

    Ischemic colitis appears to be a collection of diseases rather than a single entity. On the one hand, there is the colitis that truly appears to be caused by a lack of blood flow and, on the other hand, there is the disease that is called "ischemic" for lack of a better diagnosis-the colitis that is more "idiopathic" than "ischemic." Four widely held tenets of "ischemic" colitis are wrong: 1) the colon is not particularly sensitive to ischemia; 2) ischemic colitis is rarely preceded by a period of global hypoperfusion; 3) the "watershed areas" are not disproportionately affected; and 4) colonoscopy with biopsy is not specific for the disease. The cause of "ischemic" colitis is unknown. Therefore it is, until proven otherwise, "acute idiopathic colitis."

  7. Familial Microscopic Colitis

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    Ayman Assad Abdo

    2001-01-01

    Full Text Available Collagenous and lymphocytic colitis are two inflammatory conditions of the colon that are often collectively referred to as microscopic colitis. The present report describes what is believed to be the third published case of familial microscopic colitis. A 55-year-old woman who suffered from chronic diarrhea was diagnosed with lymphocytic colitis on colonic biopsy. Subsequently, her 36-year-old daughter was diagnosed with collagenous colitis. The familial occurrence of these diseases may support an immunological hypothesis for their etiology. In addition, it supports the assumption that collagenous and lymphocytic colitis are two manifestations of the same disease process rather than two completely separate entities. The familial tendency of this disease may make a case for early colonoscopy and biopsy in relatives of patients diagnosed with microscopic colitis if they present with suggestive symptoms.

  8. Apple polyphenols require T cells to ameliorate dextran sulfate sodium-induced colitis and dampen proinflammatory cytokine expression.

    Science.gov (United States)

    Skyberg, Jerod A; Robison, Amy; Golden, Sarah; Rollins, Maryclare F; Callis, Gayle; Huarte, Eduardo; Kochetkova, Irina; Jutila, Mark A; Pascual, David W

    2011-12-01

    Human IBD, including UC and Crohn's disease, is characterized by a chronic, relapsing, and remitting condition that exhibits various features of immunological inflammation and affects at least one/1000 people in Western countries. Polyphenol extracts from a variety of plants have been shown to have immunomodulatory and anti-inflammatory effects. In this study, treatment with APP was investigated to ameliorate chemically induced colitis. Oral but not peritoneal administration of APP during colitis induction significantly protected C57BL/6 mice against disease, as evidenced by the lack of weight loss, colonic inflammation, and shortening of the colon. APP administration dampened the mRNA expression of IL-1β, TNF-α, IL-6, IL-17, IL-22, CXCL9, CXCL10, CXCL11, and IFN-γ in the colons of mice with colitis. APP-mediated protection requires T cells, as protection was abated in Rag-1(-/-) or TCRα(-/-) mice but not in IL-10(-/-), IRF-1(-/-), μMT, or TCRδ(-/-) mice. Administration of APP during colitis to TCRα(-/-) mice actually enhanced proinflammatory cytokine expression, further demonstrating a requirement for TCRαβ cells in APP-mediated protection. APP treatment also inhibited CXCR3 expression by TCRαβ cells, but not B or NK cells, in the colons of mice with colitis; however, depletion of CD4(+) or CD8(+) T cells alone did not abolish APP-mediated protection. Collectively, these results show that oral administration of APP protects against experimental colitis and diminishes proinflammatory cytokine expression via T cells.

  9. Colitis promotes adaptation of an intestinal nematode: a Heligmosomoides polygyrus mouse model system.

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    Katarzyna Donskow-Łysoniewska

    Full Text Available The precise mechanism of the very effective therapeutic effect of gastrointestinal nematodes on some autoimmune diseases is not clearly understood and is currently being intensively investigated. Treatment with living helminths has been initiated to reverse intestinal immune-mediated diseases in humans. However, little attention has been paid to the phenotype of nematodes in the IBD-affected gut and the consequences of nematode adaptation. In the present study, exposure of Heligmosomoides polygyrus larvae to the changed cytokine milieu of the intestine during colitis reduced inflammation in an experimental model of dextran sulphate sodium (DSS- induced colitis, but increased nematode establishment in the moderate-responder BALB/c mouse strain. We used mass spectrometry in combination with two-dimensional Western blotting to determine changes in protein expression and changes in nematode antigens recognized by IgG1 in mice with colitis. We show that nematode larvae immunogenicity is changed by colitis as soon as 6 days post-infection; IgG1 did not recognize highly conserved proteins Lev-11 (isoform 1 of tropomyosin α1 chain, actin-4 isoform or FTT-2 isoform a (14-3-3 family protein. These results indicate that changes in the small intestine provoked by colitis directly influence the nematode proteome. The unrecognized proteins seem to be key antigenic epitopes able to induce protective immune responses. The proteome changes were associated with weak immune recognition and increased larval adaptation and worm growth, altered localization in the intestine and increased survival of males but reduced worm fecundity. In this report, the mechanisms influencing nematode survival and the consequences of changed immunogenicity that reflect the immune response at the site colonized by the parasite in mice with colitis are described. The results are relevant to the use of live parasites to ameliorate IBD.

  10. Beneficial Effect of Voluntary Exercise on Experimental Colitis in Mice Fed a High-Fat Diet: The Role of Irisin, Adiponectin and Proinflammatory Biomarkers.

    Science.gov (United States)

    Mazur-Bialy, Agnieszka Irena; Bilski, Jan; Wojcik, Dagmara; Brzozowski, Bartosz; Surmiak, Marcin; Hubalewska-Mazgaj, Magdalena; Chmura, Anna; Magierowski, Marcin; Magierowska, Katarzyna; Mach, Tomasz; Brzozowski, Tomasz

    2017-04-20

    Inflammatory bowel diseases (IBDs) are a heterogeneous group of disorders exhibited by two major phenotypic forms: Crohn's disease and ulcerative colitis. Although the aetiology of IBD is unknown, several factors coming from the adipose tissue and skeletal muscles, such as cytokines, adipokines and myokines, were suggested in the pathogenesis of ulcerative colitis; however, it has not been extensively studied whether voluntary exercise can ameliorate that disorder. We explored the effect of moderate exercise (i.e., voluntary wheel running) on the disease activity index (DAI), colonic blood flow (CBF), plasma irisin and adiponectin levels and real-time PCR expression of proinflammatory markers in mesenteric fat in mice with 2,4,6-trinitrobenzenesulfonic acid (TNBS) colitis fed a high-fat diet (HFD) compared to those on a standard chow diet (SD). Macroscopic and microscopic colitis in sedentary SD mice was accompanied by a significant fall in CBF, some increase in colonic tissue weight and a significant increase in the plasma levels of tumour necrosis factor-alpha (TNF-α), IL-6, monocyte chemotactic protein 1 (MCP-1) and IL-13 (p colitis, substantially increased CBF and attenuated the plasma TNF-α, IL-6, MCP-1, IL-1β and leptin levels while raising the plasma irisin and the plasma and WAT concentrations of adiponectin in HFD mice (p colitis is exacerbated in HFD mice, possibly due to a fall in colonic microcirculation and an increase in the plasma and mesenteric fat content of proinflammatory biomarkers; and (2) voluntary physical activity can attenuate the severity of colonic damage in mice fed a HFD through the release of protective irisin and restoration of plasma adiponectin.

  11. O papel do óxido nítrico na pressão anal esfincteriana de ratos submetidos à colite experimental The role of nitric oxide in sphincteric anal pressure of rats with experimental colitis

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    Henrique Sarubbi Fillmann

    2006-12-01

    organism. It presents with an ample specter of physiological actions being the most important its mechanism of action in the relaxation of the smooth musculature, its neurotransmissor activity in some systems and its involvement in the inflammatory process. The NO is synthesized in different tissues by the conversion of the L-arginine in L-citruline with the action of the enzyme nitric oxide sintase(NOS. OBJECTIVES: the aim of this study is to demonstrate the involvement of nitric oxide in the inflammatory intestinal process of Wistar rats submitted to experimental colitis with ascetic acid. MATERIAL AND METHODS: 20 male Wistar rats had been used with weight between 250 and 350 g divided in two groups of 10 animals. The animals of the group in study had been submitted to intracolonic administration, by enema, of a solution with acid ascetic diluted to 7% - 3 ml. The control group received only enema with saline solution. The histological scores, the expression of the enzyme nitric oxide sintase (iNOS and the sphincteric anal pressure had been evaluated. RESULTS: The histological scores had presented a significant rise in the group colitis when compared with the control group in the macroscopic as well as in the microscopical evaluation. The expression of the enzyme iNOS was also significantly higher in the colitis group when compared to the control group. The sphincteric anal pressure was significantly lower in the group colitis when compared to control group. CONCLUSION: The animals submitted to the experimental colitis presented an increase of the iNOS expression. This increase, associated with the consequent increase in nitric oxide level, causes a reduction of the sphincteric anal pressure levels.

  12. Lactobacillus GG prevents recurrence of colitis in HLA-B27 transgenic rats after antibiotic treatment

    NARCIS (Netherlands)

    Dieleman, L. A.; Goerres, M. S.; Arends, A.; Sprengers, D.; Torrice, C.; Hoentjen, F.; Grenther, W. B.; Sartor, R. B.

    2003-01-01

    Bacteroides vulgatus induces colitis in gnotobiotic HLA-B27 transgenic (TG) rats while broad spectrum antibiotics prevent and treat colitis in specific pathogen free (SPF) TG rats although disease recurs after treatment ends. Lactobacilli treat human pouchitis and experimental colitis. We

  13. miR-200b-containing microvesicles attenuate experimental colitis associated intestinal fibrosis by inhibiting epithelial-mesenchymal transition.

    Science.gov (United States)

    Yang, Jia; Zhou, Cheng-Zhi; Zhu, Rui; Fan, Heng; Liu, Xing-Xing; Duan, Xue-Yun; Tang, Qing; Shou, Zhe-Xing; Zuo, Dong-Mei

    2017-12-01

    Epithelial-mesenchymal transition (EMT), characterized by the decrease of E-cadherin (E-Cad) and increase in vimentin and alpha-smooth muscle actin (α-SMA), was demonstrated to participate in inflammatory bowel disease-related fibrosis. miR-200b plays an anti-fibrosis role in inhibiting EMT by targeting ZEB1 and ZEB2. But the stability of exogenous miR-200b in blood limits its application. Microvesicles (MVs), which can transfer miRNAs among cells and prevent them from degradation, may provide an excellent transport system for the delivery of miR-200b in the treatment of fibrosis. Bone marrow mesenchymal stem cells (BMSCs) were transfected with lentivirus to overexpress miR-200b. The MVs packaged with miRNA-200b were harvested for the anti-fibrotic treatment using in vitro (transforming growth factor beta 1-mediated EMT in intestinal epithelial cells: IEC-6) and in vivo (TNBS-induced intestinal fibrosis in rats) models. The pathological morphology was observed, and the fibrosis related proteins, such as E-Cad, vimentin, α-SMA, ZEB1, and ZEB2, were detected. MiR-200b-MVs would significantly reverse the morphology in TGF-β1-treated IEC-6 cells and improve the TNBS-induced colon fibrosis histologically. The treatment of miR-200b-MVs increased miR-200b levels both in the IEC-6 cells and colon, resulting in a significant prevention EMT and alleviation of fibrosis. The expression of E-Cad was increased, and the expressions of vimentin and α-SMA were decreased. ZBE1 and ZEB2, the targets of miR-200b, were also decreased. miR-200b could be transferred from genetically modified BMSCs to the target cells or tissue by MVs. The mechanisms of miR-200b-MVs in inhibiting colonic fibrosis were related to suppressing the development of EMT by targeting ZEB1and ZEB2. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  14. IL17 Mediates Pelvic Pain in Experimental Autoimmune Prostatitis (EAP.

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    Stephen F Murphy

    Full Text Available Chronic pelvic pain syndrome (CPPS is the most common form of prostatitis, accounting for 90-95% of all diagnoses. It is a complex multi-symptom syndrome with unknown etiology and limited effective treatments. Previous investigations highlight roles for inflammatory mediators in disease progression by correlating levels of cytokines and chemokines with patient reported symptom scores. It is hypothesized that alteration of adaptive immune mechanisms results in autoimmunity and subsequent development of pain. Mouse models of CPPS have been developed to delineate these immune mechanisms driving pain in humans. Using the experimental autoimmune prostatitis (EAP in C57BL/6 mice model of CPPS we examined the role of CD4+T-cell subsets in the development and maintenance of prostate pain, by tactile allodynia behavioral testing and flow cytometry. In tandem with increased CD4+IL17A+ T-cells upon EAP induction, prophylactic treatment with an anti-IL17 antibody one-day prior to EAP induction prevented the onset of pelvic pain. Therapeutic blockade of IL17 did not reverse pain symptoms indicating that IL17 is essential for development but not maintenance of chronic pain in EAP. Furthermore we identified a cytokine, IL7, to be associated with increased symptom severity in CPPS patients and is increased in patient prostatic secretions and the prostates of EAP mice. IL7 is fundamental to development of IL17 producing cells and plays a role in maturation of auto-reactive T-cells, it is also associated with autoimmune disorders including multiple sclerosis and type-1 diabetes. More recently a growing body of research has pointed to IL17's role in development of neuropathic and chronic pain. This report presents novel data on the role of CD4+IL17+ T-cells in development and maintenance of pain in EAP and CPPS.

  15. Essential Role of Growth Hormone and IGF-1 in Therapeutic Effect of Ghrelin in the Course of Acetic Acid-Induced Colitis.

    Science.gov (United States)

    Ceranowicz, Piotr; Warzecha, Zygmunt; Cieszkowski, Jakub; Ceranowicz, Dagmara; Kuśnierz-Cabala, Beata; Bonior, Joanna; Jaworek, Jolanta; Ambroży, Tadeusz; Gil, Krzysztof; Olszanecki, Rafał; Pihut, Małgorzata; Dembiński, Artur

    2017-05-24

    Previous studies have shown that ghrelin exhibits a protective and therapeutic effect in the gut. The aim of the present study was to examine whether administration of ghrelin affects the course of acetic acid-induced colitis and to determine what is the role of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) in this effect. In sham-operated or hypophysectomized male Wistar rats, colitis was induced by enema with 1 mL of 3% solution of acetic acid. Saline or ghrelin (given at the dose of 8 nmol/kg/dose) was administered intraperitoneally twice a day. Seven days after colitis induction, rats were anesthetized and the severity of the colitis was assessed. Treatment with ghrelin reduced the area of colonic mucosa damage in pituitary-intact rat. This effect was associated with increase in serum levels of GH and IGF-1. Moreover, administration of ghrelin improved blood flow in colonic mucosa and mucosal cell proliferation, as well as reduced mucosal concentration of proinflammatory interleukin-1β (IL-1β) and activity of myeloperoxidase. Hypophysectomy reduced serum levels of GH and IGF-1 and increased the area of colonic damage in rats with colitis. These effects were associated with additional reduction in mucosal blood follow and DNA synthesis when compared to pituitary-intact rats. Mucosal concentration of IL-1β and mucosal activity of myeloperoxidase were maximally increased. Moreover, in hypophysectomized rats, administration of ghrelin failed to affect serum levels of GH or IGF-1, as well as the healing rate of colitis, mucosal cell proliferation, and mucosal concentration of IL-1β, or activity of myeloperoxidase. We conclude that administration of ghrelin accelerates the healing of the acetic acid-induced colitis. Therapeutic effect of ghrelin in experimental colitis is mainly mediated by the release of endogenous growth hormone and IGF-1.

  16. Does oral exposure to cadmium and lead mediate susceptibility to colitis? The dark-and-bright sides of heavy metals in gut ecology

    Science.gov (United States)

    Breton, Jérôme; Daniel, Catherine; Vignal, Cécile; Body-Malapel, Mathilde; Garat, Anne; Plé, Coline; Foligné, Benoît

    2016-01-01

    Although the heavy metals cadmium (Cd) and lead (Pb) are known environmental health concerns, their long-term impacts on gut ecology and susceptibility to gastrointestinal autoimmune diseases have not been extensively investigated. We sought to determine whether subchronic oral exposure to Cd or Pb is a risk factor for the development and progression of inflammatory bowel disease (IBD). Mice were exposed to various doses of CdCl2 or PbCl2 in drinking water for 1, 4 or 6 weeks prior to infection with Salmonella, the induction of colitis with dextran sodium sulfate (DSS) or trinitrobenzene sulfonic acid (TNBS). In human cell-based models, exposure to Cd and Pb is associated with reduced transepithelial electric resistance and changes in bacteria-induced cytokine responses. Although 1- and 6-week exposures did not have clear effects on the response to Salmonella infectious challenges, 1-week short-term treatments with CdCl2 tended to enhance intestinal inflammation in mice. Unexpectedly, subchronic exposure to Cd and (to a lesser extent) Pb significantly mitigated some of the symptoms of DSS-induced colitis and reduced the severity of TNBS colitis in a dose-dependent manner. The possible adaptive and immunosuppressive mechanisms by which heavy metals might reduce intestinal inflammation are explored and discussed.

  17. Influence of the peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist, rosiglitazone and antagonist, biphenol-A-diglicydyl ether (BADGE) on the course of inflammation in the experimental model of colitis in rats.

    Science.gov (United States)

    Dworzanski, T; Celinski, K; Korolczuk, A; Slomka, M; Radej, S; Czechowska, G; Madro, A; Cichoz-Lach, H

    2010-12-01

    PPAR-γ plays a role in the development of immune response, particularly in inflammation. The inflammatory reaction may be stimulated or suppressed by the presence of PPAR ligands. Some researchers suggest positive influence of the PPAR-γ agonist on suppression of the intestinal inflammatory process, yet there has not been much evidence showing that the antagonist of PPAR-γ can affect the inflammatory process. The aim of the present study was to define the mechanism by which PPAR-γ ligands affect the course of experimentally induced colitis in rats. Colitis was induced in rats by rectal administration of TNBS (trinitrobenzene sulfonate). Rosiglitazone was administrated to animals at the dose of 8 mg/kg four times via an intra-gastric probe. Biphenol-A-diglicydyl ether (BADGE) was administrated intraperitoneally at the dose of 120 mg/kg, three times every second day. One group of animals received rosiglitazone together with BADGE before the induction of inflammation. Histological and ELISA examinations of large intestine samples were performed. Levels of IL-1β, IL-6, TNF-α cytokines were determined in serum and homogenates. Rats exposed to rosiglitazone had higher body weight yet lower large intestine weight. Histological findings showed less ulceration, lower expression of crypts' loss and smaller oedema. Animals, which did not receive rosiglitazone, and those receiving it together with BADGE, developed more severe inflammatory changes. Rosiglitazone decreased the expression of inflammatory cytokines, such as IL-6 and TNF-α, both in serum and in intestinal homogenates. BADGE used with TNBS did not increase the expression of inflammatory cytokines; however, applied together with rosiglitazone, it caused inflammation similar to that observed among rats with experimentally induced colitis. Rosiglitazone reduces inflammation by decreasing the expression of IL-6 and TNF-α. BADGE administered with rosiglitazone blocks the activity of PPAR-γ and abolishes the

  18. Technical Advance: Function and efficacy of an {alpha}4-integrin antagonist using bioluminescence imaging to detect leukocyte trafficking in murine experimental colitis.

    Science.gov (United States)

    Murphy, Carola T; Moloney, Gerard; Macsharry, John; Haynes, Andrea; Faivre, Emilie; Quinlan, Aoife; McLean, Peter G; Lee, Kevin; O'Mahony, Liam; Shanahan, Fergus; Melgar, Silvia; Nally, Kenneth

    2010-12-01

    Leukocyte trafficking is a therapeutic target in IBD. The integrins α₄β and α₄β₁ regulate leukocyte migration into tissues and lymphoid organs. Current strategies rely on biologics, such as mAb, to inhibit leukocyte recruitment. Here we show the in vivo therapeutic effects of a small molecule α4-integrin antagonist (GSK223618A) in a leukocyte-trafficking model and a murine model of colitis. Leukocytes isolated from MLNs of transgenic β-actin-luc+ mice were injected i.v. into recipients with DSS-induced colitis. Recipient mice were orally gavaged with vehicle or an α₄-integrin antagonist 1 h pre-adoptive transfer, followed by bioluminescence whole body and ex vivo organ imaging 4 h post-transfer. To confirm its therapeutic effect, the α₄-integrin antagonist was given orally twice daily for 6 days to mice with DSS-induced colitis, starting on Day 3. Clinical, macroscopic, and histological signs of inflammation were assessed and gene-expression profiles analyzed. Using bioluminescence imaging, we tracked and quantified leukocyte migration to the inflamed gut and demonstrated its inhibition by a small molecule α₄-integrin antagonist. Additionally, the therapeutic effect of the antagonist was confirmed in DSS-induced colitis in terms of clinical, macroscopic, and histological signs of inflammation. Gene expression analysis suggested enhancement of tissue healing in compound-treated animals. Inhibition of leukocyte trafficking using small molecule integrin antagonists is a promising alternative to large molecule biologics. Furthermore, in vivo bioluminescence imaging is a valuable strategy for preclinical evaluation of potential therapeutics that target leukocyte trafficking in inflammatory diseases.

  19. The C-type lectin receptor SIGNR3 binds to fungi present in commensal microbiota and influences immune regulation in experimental colitis

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    Magdalena eEriksson

    2013-07-01

    Full Text Available Inflammatory bowel disease is a condition of acute and chronic inflammation of the gut. An important factor contributing to pathogenesis is a dysregulated mucosal immunity against commensal bacteria and fungi. Host pattern recognition receptors sense commensals in the gut and are involved in maintaining the balance between controlled responses to pathogens and overwhelming innate immune activation. C-type lectin receptors (CLRs are pattern recognition receptors recognizing glycan structures on pathogens and self-antigens. Here we examined the role of the murine CLR SIGNR3 in the recognition of commensals and its involvement in intestinal immunity. SIGNR3 is the closest murine homologue of the human DC-SIGN receptor recognizing similar carbohydrate ligands such as terminal fucose or high-mannose glycans. We discovered that SIGNR3 recognizes fungi present in the commensal microbiota. To analyze if this interaction impacts the intestinal immunity against microbiota, the dextran sulfate sodium (DSS-induced colitis model was employed. SIGNR3-/- mice exhibited an increased weight loss associated with more severe colitis symptoms compared to wild-type control mice. The increased inflammation in SIGNR3-/- mice was accompanied by a higher level of TNF-α in colon. Our findings demonstrate for the first time that SIGNR3 recognizes intestinal fungi and has an immune regulatory role in colitis.

  20. Cannabinoid receptor-2 (CB2) agonist ameliorates colitis in IL-10{sup −/−} mice by attenuating the activation of T cells and promoting their apoptosis

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    Singh, Udai P.; Singh, Narendra P. [Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC 29208 (United States); Singh, Balwan [National Primate Research Center, Emory University, Atlanta GA 30329 (United States); Price, Robert L. [Department of Cell and Developmental Biology, University of South Carolina, Columbia, SC 29208 (United States); Nagarkatti, Mitzi [Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC 29208 (United States); Nagarkatti, Prakash S., E-mail: Prakash.Nagarkatti@uscmed.sc.edu [Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC 29208 (United States)

    2012-01-15

    Inflammatory bowel disease (IBD) is a chronic intestinal inflammation caused by hyperactivated effector immune cells that produce pro-inflammatory cytokines. Recent studies have shown that the cannabinoid system may play a critical role in mediating protection against intestinal inflammation. However, the effect of cannabinoid receptor induction after chronic colitis progression has not been investigated. Here, we investigate the effect of cannabinoid receptor-2 (CB2) agonist, JWH-133, after chronic colitis in IL-10{sup −/−} mice. JWH-133 effectively attenuated the overall clinical score, and reversed colitis-associated pathogenesis and decrease in body weight in IL-10{sup −/−} mice. After JWH-133 treatment, the percentage of CD4{sup +} T cells, neutrophils, mast cells, natural killer (NK1.1) cells, and activated T cells declined in the intestinal lamina propria (LP) and mesenteric lymph nodes (MLN) of mice with chronic colitis. JWH-133 was also effective in ameliorating dextran sodium sulfate (DSS)-induced colitis. In this model, JWH-133 reduced the number and percentage of macrophages and IFN-γ expressing cells that were induced during colitis progression. Treatment with aminoalkylindole 6-iodo-pravadoline (AM630), a CB2 receptor antagonist, reversed the colitis protection provided by JWH-133 treatment. Also, activated T cells were found to undergo apoptosis following JWH-133 treatment both in-vivo and in-vitro. These findings suggest that JWH-133 mediates its effect through CB2 receptors, and ameliorates chronic colitis by inducing apoptosis in activated T cells, reducing the numbers of activated T cells, and suppressing induction of mast cells, NK cells, and neutrophils at sites of inflammation in the LP. These results support the idea that the CB2 receptor agonists may serve as a therapeutic modality against IBD. -- Highlights: ► JWH-133, a cannnabinoid receptor-2 agonist ameliorates experimental colitis. ► JWH-133 suppressed inflammation and

  1. The nature of colitis in chronic granulomatous disease.

    Science.gov (United States)

    Schäppi, Michela G; Klein, Nigel J; Lindley, Keith J; Rampling, Dyanne; Smith, Virpi V; Goldblatt, David; Milla, Peter J

    2003-05-01

    Patients with chronic granulomatous disease (CGD) may have gastrointestinal manifestations, commonly colitis. The etiology, prevalence, and inflammatory process of CGD colitis are unclear. To characterize the inflammatory process of CGD colitis and to compare it with other inflammatory bowel disorders. Colonic mucosal biopsies from 8 CGD patients were immunostained for eosinophils, neutrophils, macrophages, and adhesion molecules (ICAM; VCAM, E-selectin) and compared with normal and diseased controls (allergic colitis, ulcerative colitis, and melanosis coli). Cell types were counted and expressed as cell/mm2. The inflammatory infiltrate in CGD colitis differed from the normal controls by an increase in eosinophils (110; 48-176 [median and range] versus 14.5; 3-30; P neutrophils compared to ulcerative colitis (10; 0-101 versus 315.5; 78-688; P endothelium in CGD compared with normal controls. Patterns of expression of the adhesion molecules differed significantly in CGD from those in other inflammatory bowel diseases: intracellular adhesion molecule-1 was more strongly expressed in the lamina propria, vascular adhesion molecule-1 was more patchily expressed, and E-selectin was present only in the small vessels. The mechanism of inflammation and profile of inflammatory mediators in CGD colitis differs from that in other inflammatory bowel diseases.

  2. 6-Gingerol modulates proinflammatory responses in dextran sodium sulfate (DSS)-treated Caco-2 cells and experimental colitis in mice through adenosine monophosphate-activated protein kinase (AMPK) activation.

    Science.gov (United States)

    Chang, Kuei-Wen; Kuo, Cheng-Yi

    2015-10-01

    6-gingerol has been reported to have anti-inflammatory effects in different experimental settings. The present study aimed at evaluating the effect of 6-gingerol on dextran sodium sulfate (DSS)-induced barrier impairment and inflammation in vitro and in vivo. a differentiated Caco-2 monolayer was exposed to DSS and treated with different concentrations of 6-gingerol (0, 1, 5, 10, 50, and 100 μM). Changes in intestinal barrier function were determined using transepithelial electrical resistance (TEER). The anti-inflammatory activity of 6-gingerol was examined as changes in the expression of proinflammatory cytokine using quantitative real-time PCR. Western blotting was employed to determine the activation of adenosine monophosphate-activated protein kinase (AMPK). Mice with DSS-induced colitis were given different oral dosages of 6-gingerol daily for 14 days. Body weight and colon inflammation were evaluated, and level of proinflammatory cytokines in colon tissues was measured. 6-gingerol treatment was shown to restore impaired intestinal barrier function and to suppress proinflammatory responses in DSS-treated Caco-2 monolayers. We found that AMPK was activated on 6-gingerol treatment in vitro. In animal studies, 6-gingerol significantly ameliorated DSS-induced colitis by restoration of body weight loss, reduction in intestinal bleeding, and prevention of colon length shortening. In addition, 6-gingerol suppressed DSS-elevated production of proinflammatory cytokines (IL-1β, TNFα, and IL-12). our findings highlight the protective effects of 6-gingerol against DSS-induced colitis. We concluded that 6-gingerol exerts anti-inflammatory effects through AMPK activation. It is suggested that 6-gingerol has a promising role in treatment of IBD.

  3. 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.

  4. Dysplasia in Ulcerative Colitis

    OpenAIRE

    RH Riddell

    1990-01-01

    Patients at highest risk for developing cancer in ulcerative colitis are those with ‘extensive’ or total involvement of the large bowel who have had the disease for at least seven years. Dysplasia is used as a marker bur has many problems including those of sampling, reproducibility and management. The risk in patients with colitis is unclear particularly in those with left-sided or distal ulcerative colitis. In countries at high risk from colorectal cancer about 4 to 6% of the population can...

  5. Experimental Pseudomonas aeruginosa mediated rhino sinusitis in mink

    DEFF Research Database (Denmark)

    Kirkeby, S.; Hammer, A. S.; Høiby, N.

    2017-01-01

    The nasal and sinus cavities in children may serve as reservoirs for microorganisms that cause recurrent and chronic lung infections. This study evaluates whether the mink can be used as an animal model for studying Pseudomonas aeruginosa mediated rhino-sinusitis since there is no suitable...... in the infected mink shows features of carbohydrate expression comparable to what has been described in the respiratory system after Pseudomonas aeruginosa infection in humans. It is suggested that the mink is suitable for studying Pseudomonas aeruginosa mediated rhino-sinusitis....... traditional animal model for this disease. Nasal tissue samples from infected and control mink were fixed in formalin, demineralized, and embedded in paraffin. A histological examination of sections from the infected animals revealed disintegration of the respiratory epithelium lining the nasal turbinates...

  6. Reduced Epithelial Na+/H+ Exchange Drives Gut Microbial Dysbiosis and Promotes Inflammatory Response in T Cell-Mediated Murine Colitis.

    Directory of Open Access Journals (Sweden)

    Daniel Laubitz

    Full Text Available Inflammatory bowel diseases (IBD are associated with functional inhibition of epithelial Na+/H+ exchange. In mice, a selective disruption of NHE3 (Slc9a3, a major apical Na+/H+ exchanger, also promotes IBD-like symptoms and gut microbial dysbiosis. We hypothesized that disruption of Na+/H+ exchange is necessary for the development of dysbiosis, which promotes an exacerbated mucosal inflammatory response. Therefore, we performed a temporal analysis of gut microbiota composition, and mucosal immune response to adoptive T cell transfer was evaluated in Rag2-/- and NHE3-/-/Rag2-/- (DKO mice with and without broad-spectrum antibiotics. Microbiome (16S profiling, colonic histology, T cell and neutrophil infiltration, mucosal inflammatory tone, and epithelial permeability were analyzed. In adoptive T cell transfer colitis model, Slc9a3 status was the most significant determinant of gut microbial community. In DKO mice, NHE3-deficiency and dysbiosis were associated with dramatically accelerated and exacerbated disease, with rapid body weight loss, increased mucosal T cell and neutrophil influx, increased mucosal cytokine expression, increased permeability, and expansion of CD25-FoxP3+ Tregs; this enhanced susceptibility was alleviated by oral broad-spectrum antibiotics. Based on these results and our previous work, we postulate that epithelial electrolyte homeostasis is an important modulator in the progression of colitis, acting through remodeling of the gut microbial community.

  7. Colonization of C57BL/6 Mice by a Potential Probiotic Bifidobacterium bifidum Strain under Germ-Free and Specific Pathogen-Free Conditions and during Experimental Colitis.

    Directory of Open Access Journals (Sweden)

    Verena Grimm

    Full Text Available The effects of at least some probiotics are restricted to live, metabolically active bacteria at their site of action. Colonization of and persistence in the gastrointestinal tract is thus contributing to the beneficial effects of these strains. In the present study, colonization of an anti-inflammatory Bifidobacterium bifidum strain was studied in C57BL/6J mice under germ-free (GF and specific pathogen-free (SPF conditions as well as during dextran sulfate sodium (DSS-induced colitis. B. bifidum S17/pMGC was unable to stably colonize C57BL/6J mice under SPF conditions. Mono-association of GF mice by three doses on consecutive days led to long-term, stable detection of up to 109 colony forming units (CFU of B. bifidum S17/pMGC per g feces. This stable population was rapidly outcompeted upon transfer of mono-associated animals to SPF conditions. A B. animalis strain was isolated from the microbiota of these re-conventionalized mice. This B. animalis strain displayed significantly higher adhesion to murine CMT-93 intestinal epithelial cells (IECs than to human Caco-2 IECs (p = 0.018. Conversely, B. bifidum S17/pMGC, i.e., a strain of human origin, adhered at significantly higher levels to human compared to murine IECs (p < 0.001. Disturbance of the gut ecology and induction of colitis by DSS-treatment did not promote colonization of the murine gastrointestinal tract (GIT by B. bifidum S17/pMGC. Despite its poor colonization of the mouse GIT, B. bifidum S17/pMGC displayed a protective effect on DSS-induced colitis when administered as viable bacteria but not as UV-inactivated preparation. Collectively, these results suggest a selective disadvantage of B. bifidum S17/pMGC in the competition with the normal murine microbiota and an anti-inflammatory effect that requires live, metabolically active bacteria.

  8. Loss of Dok-1 and Dok-2 in mice causes severe experimental colitis accompanied by reduced expression of IL-17A and IL-22

    Energy Technology Data Exchange (ETDEWEB)

    Waseda, Masazumi; Arimura, Sumimasa [Division of Genetics, Department of Cancer Biology, The Institute of Medical Science, The University of Tokyo, Shirokanedai, Minato-ku, Tokyo, 108-8639 (Japan); Shimura, Eri [Laboratory of Systems Biology, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, Shirokanedai, Minato-ku, Tokyo, 108-8639 (Japan); Nakae, Susumu [Laboratory of Systems Biology, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, Shirokanedai, Minato-ku, Tokyo, 108-8639 (Japan); Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency, Saitama, 332-0012 (Japan); Yamanashi, Yuji, E-mail: yyamanas@ims.u-tokyo.ac.jp [Division of Genetics, Department of Cancer Biology, The Institute of Medical Science, The University of Tokyo, Shirokanedai, Minato-ku, Tokyo, 108-8639 (Japan)

    2016-09-09

    Appropriate immune responses and mucosal barrier functions are required for the maintenance of intestinal homeostasis. Defects in this defense system may lead to inflammatory disorders such as inflammatory bowel disease. Downstream of tyrosine kinases 1 (Dok-1) and its closest homolog, Dok-2, are preferentially expressed in immune cells, and play essential roles in the negative regulation of multiple signaling pathways in both innate and adaptive immunity. However, the function of these proteins in intestinal homeostasis remained unclear. Here we show that Dok-1/-2 double knockout (DKO) mice were highly susceptible to dextran sodium sulfate (DSS)-induced colitis compared with Dok-1 or Dok-2 single KO and wild type (WT) mice. Furthermore, DSS-treated Dok-1/-2 DKO mice exhibited increased colonic tissue damage accompanied by reduced proliferation of the epithelial cells relative to WT controls, suggesting that Dok-1/-2 DKO mice have defects in the repair of intestinal epithelial lesions. In addition, the levels of the Th17 cytokines IL-17A and IL-22, which have protective roles in DSS-induced colitis, were reduced in DSS-treated Dok-1/-2 DKO mice compared with WT mice. Taken together, our results demonstrate that Dok-1 and Dok-2 negatively regulate intestinal inflammation, apparently through the induction of IL-17A and IL-22 expression. - Highlights: • Dok-1 and Dok-2 play a cooperative role in protection against DSS-induced colitis. • Dok-1/-2 double KO (DKO) mice show extensive ulceration of the colon after DSS treatment. • Proliferation of colonic epithelium is inhibited in DSS-treated Dok-1/-2 DKO mice. • Expression of IL-17A and IL-22 is reduced in the colon of DSS-treated Dok-1/-2 DKO mice.

  9. Encenicline, an α7 Nicotinic Acetylcholine Receptor Partial Agonist, Reduces Immune Cell Infiltration in the Colon and Improves Experimental Colitis in Mice

    DEFF Research Database (Denmark)

    Salaga, M; Blomster, L V; Piechota-Polańczyk, A

    2016-01-01

    as myeloperoxidase (MPO) activity were recorded. Immunohistochemistry (IHC) was used to measure the infiltration of immune cells in the colon. Furthermore, we employed flow cytometry to determine the effect of encenicline on frequencies of FoxP3(+) and interleukin (IL)-17A(+) T cells in the mouse colon. Encenicline....... In the TNBS model encenicline reduced the frequency of FoxP3(+) IL-17A(+) T cells in the colon. In the DSS-model treatment encenicline increased the frequency of FoxP3(+) T cells and reduced IL-17A(+) T cells. Stimulation of α7 nAChR with partial agonist encenicline alleviates colitis via alteration...

  10. Lubiprostone induced ischemic colitis.

    Science.gov (United States)

    Sherid, Muhammed; Sifuentes, Humberto; Samo, Salih; Deepak, Parakkal; Sridhar, Subbaramiah

    2013-01-14

    Ischemic colitis accounts for 6%-18% of the causes of acute lower gastrointestinal bleeding. It is often multifactorial and more commonly encountered in the elderly. Several medications have been implicated in the development of colonic ischemia. We report a case of a 54-year old woman who presented with a two-hour history of nausea, vomiting, abdominal pain, and bloody stool. The patient had recently used lubiprostone with close temporal relationship between the increase in the dose and her symptoms of rectal bleeding. The radiologic, colonoscopic and histopathologic findings were all consistent with ischemic colitis. Her condition improved without any serious complications after the cessation of lubiprostone. This is the first reported case of ischemic colitis with a clear relationship with lubiprostone (Naranjo score of 10). Clinical vigilance for ischemic colitis is recommended for patients receiving lubiprostone who are presenting with abdominal pain and rectal bleeding.

  11. Right dorsal colitis

    National Research Council Canada - National Science Library

    Karcher, L F; Dill, S G; Anderson, W I; King, J M

    1990-01-01

    Moderate to severe ulcerative colitis of the right dorsal colon was diagnosed by necropsy or by exploratory celiotomy and biopsy in 13 horses with a primary clinical complaint of either colic, diarrhea, or weight loss...

  12. Experimental Pseudomonas aeruginosa mediated rhino sinusitis in mink.

    Science.gov (United States)

    Kirkeby, S; Hammer, A S; Høiby, N; Salomonsen, C M

    2017-05-01

    The nasal and sinus cavities in children may serve as reservoirs for microorganisms that cause recurrent and chronic lung infections. This study evaluates whether the mink can be used as an animal model for studying Pseudomonas aeruginosa mediated rhino-sinusitis since there is no suitable traditional animal model for this disease. Nasal tissue samples from infected and control mink were fixed in formalin, demineralized, and embedded in paraffin. A histological examination of sections from the infected animals revealed disintegration of the respiratory epithelium lining the nasal turbinates and swelling and edema of the submucosa. The expression of mucins and sialylated glycans was examined using immunohistochemistry. MUC1, MUC2 and MUC5AC were upregulated in the inoculated animals as a much stronger staining was present in the respiratory epithelium in the infected animals compared to the controls. The goblet cells in the nasal epithelium from the infected mink showed high affinity to the Maackia amurensis lectin and anti-asialo GM1 indicating a high concentration of α2-3 sialic acid respectively βGalNAc1-4Galβ containing glycans in these mucin producing cells. The nasal cavity in the infected mink shows features of carbohydrate expression comparable to what has been described in the respiratory system after Pseudomonas aeruginosa infection in humans. It is suggested that the mink is suitable for studying Pseudomonas aeruginosa mediated rhino-sinusitis. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  13. Protective effect of cavidine on acetic acid-induced murine colitis via regulating antioxidant, cytokine profile and NF-κB signal transduction pathways.

    Science.gov (United States)

    Niu, Xiaofeng; Zhang, Hailin; Li, Weifeng; Wang, Yu; Mu, Qingli; Wang, Xiumei; He, Zehong; Yao, Huan

    2015-09-05

    Ulcerative colitis is an inflammatory disorder characterized by neutrophils infiltration, oxidative stress, upregulation of pro-inflammatory mediators and cytokines. Cavidine possesses anti-inflammatory activity and has been used to treat various inflammatory diseases but its effect on ulcerative colitis has not been previously explored. The present study aims to evaluate the effect of cavidine on acetic acid-induced ulcerative colitis in mice. Colitis mice induced by intra-rectal acetic acid (5%, v/v) administration received cavidine (1, 5 and 10mg/kg, i.g) or sulfasalazine (500mg/kg, i.g) for seven consecutive days. After euthanized by cervical dislocation, colonic segments of mice were excised for clinical, macroscopic, biochemical and histopathological examinations. Results suggested treatment with cavidine significantly decreased mortality rate, body weight loss, disease activity index (DAI), wet colon weight, macroscopic and histological score when compared with that of acetic acid-induced controls. In addition, administration of cavidine effectively modulated expressions of MPO, GSH, SOD and MDA. Furthermore cavidine inhibited the level of TNF-α and IL-6 in the serum and colon tissue in response to the regulation of p65 NF-κB protein expression. All these results indicated cavidine exerts marked protective effect in experimental colitis, possibly by regulating the expression of oxygen metabolites, NF-κB and subsequent pro-inflammatory cytokines production. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  14. Curcuma longa extract exerts a myorelaxant effect on the ileum and colon in a mouse experimental colitis model, independent of the anti-inflammatory effect.

    Science.gov (United States)

    Aldini, Rita; Budriesi, Roberta; Roda, Giulia; Micucci, Matteo; Ioan, Pierfranco; D'Errico-Grigioni, Antonia; Sartini, Alessandro; Guidetti, Elena; Marocchi, Margherita; Cevenini, Monica; Rosini, Francesca; Montagnani, Marco; Chiarini, Alberto; Mazzella, Giuseppe

    2012-01-01

    Curcuma has long been used as an anti-inflammatory agent in inflammatory bowel disease. Since gastrointestinal motility is impaired in inflammatory states, the aim of this work was to evaluate if Curcuma Longa had any effect on intestinal motility. The biological activity of Curcuma extract was evaluated against Carbachol induced contraction in isolated mice intestine. Acute and chronic colitis were induced in Balb/c mice by Dextran Sulphate Sodium administration (5% and 2.5% respectively) and either Curcuma extract (200 mg/kg/day) or placebo was thereafter administered for 7 and 21 days respectively. Spontaneous contractions and the response to Carbachol and Atropine of ileum and colon were studied after colitis induction and Curcuma administration. Curcuma extract reduced the spontaneous contractions in the ileum and colon; the maximal response to Carbachol was inhibited in a non-competitive and reversible manner. Similar results were obtained in ileum and colon from Curcuma fed mice. DSS administration decreased the motility, mainly in the colon and Curcuma almost restored both the spontaneous contractions and the response to Carbachol after 14 days assumption, compared to standard diet, but a prolonged assumption of Curcuma decreased the spontaneous and Carbachol-induced contractions. Curcuma extract has a direct and indirect myorelaxant effect on mouse ileum and colon, independent of the anti-inflammatory effect. The indirect effect is reversible and non-competitive with the cholinergic agent. These results suggest the use of curcuma extract as a spasmolytic agent.

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

    Directory of Open Access Journals (Sweden)

    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.

  16. Cancer risk in collagenous colitis

    NARCIS (Netherlands)

    Chan, J. L.; Tersmette, A. C.; Offerhaus, G. J.; Gruber, S. B.; Bayless, T. M.; Giardiello, F. M.

    1999-01-01

    Collagenous colitis is a recently described form of chronic inflammatory bowel disease. Other inflammatory bowel disorders are associated with increased risk of colorectal and extracolonic malignancies, but this has not been evaluated in collagenous colitis. Colorectal and extracolonic malignancies

  17. Cytomegalovirus Colitis in Immunocompetent Patients

    OpenAIRE

    Inayat, Faisal; Hussain, Qulsoom; Shafique, Khurram; Tasleem, Syed H; Hurairah, Abu

    2016-01-01

    Cytomegalovirus colitis is common in immunocompromised patients, but rare in immunocompetent patients. The present study not only represents the colonoscopy and pathological findings, but also applies the method of diagnosing and treating cytomegalovirus colitis in immunocompetent patients.

  18. Cytomegalovirus Colitis in Immunocompetent Patients

    Science.gov (United States)

    Hussain, Qulsoom; Shafique, Khurram; Tasleem, Syed H; Hurairah, Abu

    2016-01-01

    Cytomegalovirus colitis is common in immunocompromised patients, but rare in immunocompetent patients. The present study not only represents the colonoscopy and pathological findings, but also applies the method of diagnosing and treating cytomegalovirus colitis in immunocompetent patients. PMID:27980888

  19. 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....

  20. 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...

  1. Experimental Model of Intervertebral Disk Mediated Postoperative Epidural Fibrosis.

    Science.gov (United States)

    Larionov, Sergey N; Sorokovikov, V A; Erdyneyev, K C; Lepekhova, S A; Goldberg, O A

    2016-07-01

    Postoperative epidural fibrosis (EF) after lumbar discectomy is the most common and at the same time controversial issue. The etiology and pathogenesis creates a lot of discussion and selection of methods of treatment and prevention continues. LIV laminectomy with dura mater (DM) exposition was done in 24 rats, and then, 0.3 ml of elements of suspension of autologous intervertebral disk was implicated on DM. As autologous intervertebral disk, we used the intervertebral disk from amputated tail. In all the animals, incisions were closed with 3/0 Vicryl. EF was examined. Fibroblast cell density was calculated in each field at ×40 magnification: Grade 1 - fewer than 100 fibroblasts in each field; Grade 2 - 100-150 fibroblasts in each field; Grade 3 - more than 150 fibroblasts in each field. Based on histological results, we confirmed our model of experiment. On the 30th day of evaluation, there were significant histological evidences of postoperative epidural adhesions in experimental animals, which included the obliteration of epidural space, the presence of adhesions in the dura and nerve roots, the restructuring of the yellow ligament, bone sclerosis, excessive appearance of fibrous tissue around the autologous intervertebral disk tissue that applied on the DM. In our work, we describe a new experimental model, where the elements of autologous intervertebral disk play the role of inflammation trigger, which cause postoperative scar and EF.

  2. [Coffee enema induced acute colitis].

    Science.gov (United States)

    Lee, Chang Jung; Song, Seung Kyun; Jeon, Jin Ho; Sung, Mi Kyung; Cheung, Dae Young; Kim, Jin Il; Kim, Jae Kwang; Lee, Youn Soo

    2008-10-01

    Rectal enema used for diagnostic and therapeutic purposes infrequently causes colitis. In medical practice, enemas are known to incidentally bring about colitis by mechanical, thermal, or direct chemical injuries. Coffee enema is told to ameliorate the constipation in alternative medicine. We hereby report a case of acute colitis resulting from coffee enema, which was presented with severe abdominal pain and hematochezia.

  3. Colonization of C57BL/6 Mice by a Potential Probiotic Bifidobacterium bifidum Strain under Germ-Free and Specific Pathogen-Free Conditions and during Experimental Colitis.

    Science.gov (United States)

    Grimm, Verena; Radulovic, Katarina; Riedel, Christian U

    2015-01-01

    The effects of at least some probiotics are restricted to live, metabolically active bacteria at their site of action. Colonization of and persistence in the gastrointestinal tract is thus contributing to the beneficial effects of these strains. In the present study, colonization of an anti-inflammatory Bifidobacterium bifidum strain was studied in C57BL/6J mice under germ-free (GF) and specific pathogen-free (SPF) conditions as well as during dextran sulfate sodium (DSS)-induced colitis. B. bifidum S17/pMGC was unable to stably colonize C57BL/6J mice under SPF conditions. Mono-association of GF mice by three doses on consecutive days led to long-term, stable detection of up to 109 colony forming units (CFU) of B. bifidum S17/pMGC per g feces. This stable population was rapidly outcompeted upon transfer of mono-associated animals to SPF conditions. A B. animalis strain was isolated from the microbiota of these re-conventionalized mice. This B. animalis strain displayed significantly higher adhesion to murine CMT-93 intestinal epithelial cells (IECs) than to human Caco-2 IECs (p = 0.018). Conversely, B. bifidum S17/pMGC, i.e., a strain of human origin, adhered at significantly higher levels to human compared to murine IECs (p gastrointestinal tract (GIT) by B. bifidum S17/pMGC. Despite its poor colonization of the mouse GIT, B. bifidum S17/pMGC displayed a protective effect on DSS-induced colitis when administered as viable bacteria but not as UV-inactivated preparation. Collectively, these results suggest a selective disadvantage of B. bifidum S17/pMGC in the competition with the normal murine microbiota and an anti-inflammatory effect that requires live, metabolically active bacteria.

  4. Dyospiros kaki phenolics inhibit colitis and colon cancer cell proliferation, but not gelatinase activities.

    Science.gov (United States)

    Direito, Rosa; Lima, Ana; Rocha, João; Ferreira, Ricardo Boavida; Mota, Joana; Rebelo, Patrícia; Fernandes, Adelaide; Pinto, Rui; Alves, Paula; Bronze, Rosário; Sepodes, Bruno; Figueira, Maria-Eduardo

    2017-08-01

    Polyphenols from persimmon (Diospyros kaki) have demonstrated radical-scavenging and antiinflammatory activities; however, little is known about the effects of persimmon phenolics on inflammatory bowel diseases (IBD) and colorectal cancer (CRC). Therefore, we aimed in this work to characterize the antiinflammatory and antiproliferative effects of a persimmon phenolic extract (80% acetone in water), using an in vivo model of experimental colitis and a model of cancer cell invasion. Our results show, for the first time, a beneficial effect of a persimmon phenolic extract in the attenuation of experimental colitis and a potential antiproliferative effect on cultured colon cancer cells. Administration of persimmon phenolic extract to mice with TNBS-induced colitis led to a reduction in several functional and histological markers of colon inflammation, namely: attenuation of colon length decrease, reduction of the extent of visible injury (ulcer formation), decrease in diarrhea severity, reduced mortality rate, reduction of mucosal hemorrhage and reduction of general histological features of colon inflammation. In vitro studies also showed that persimmon phenolic extract successfully impaired cell proliferation and invasion in HT-29 cells. Further investigation showed a decreased expression of COX-2 and iNOS in the colonic tissue of colitis mice, two important mediators of intestinal inflammation, but there was no inhibition of the gelatinase MMP-9 and MMP-2 activities. Given the role of inflammatory processes in the progression of CRC and the important link between inflammation and cancer, our results highlight the potential of persimmon polyphenols as a pharmacological tool in the treatment of patients with IBD. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Endogenous Estrogen-Mediated Heme Oxygenase Regulation in Experimental Menopause

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    Anikó Pósa

    2015-01-01

    Full Text Available Estrogen deficiency is one of the main causes of age-associated diseases in the cardiovascular system. Female Wistar rats were divided into four experimental groups: pharmacologically ovariectomized, surgically ovariectomized, and 24-month-old intact aging animals were compared with a control group. The activity and expression of heme oxygenases (HO in the cardiac left ventricle, the concentrations of cardiac interleukin-6 (IL-6 and tumor necrosis factor-α (TNF-α, the myeloperoxidase (MPO activity in the cardiac left ventricle, and the effects of heme oxygenase blockade (by 24-hour and 1-hour pretreatment with tin-protoporphyrin IX, SnPP on the epinephrine and phentolamine-induced electrocardiogram ST segment changes in vivo were investigated. The cardiac HO activity and the expression of HO-1 and HO-2 were significantly decreased in the aged rats and after ovariectomy. Estrogen depletion was accompanied by significant increases in the expression of IL-6 and TNF-α. The aged and ovariectomized animals exhibited a significantly elevated MPO activity and a significant ST segment depression. After pretreatment with SnPP augmented ST segment changes were determined. These findings demonstrate that the sensitivity to cardiac ischemia in estrogen depletion models is associated with suppression of the activity and expression of the HO system and increases in the secretion of proinflammatory cytokines and biomarkers.

  6. Endogenous Estrogen-Mediated Heme Oxygenase Regulation in Experimental Menopause

    Science.gov (United States)

    Pósa, Anikó; Veszelka, Médea; Berkó, Anikó Magyariné; Baráth, Zoltán; Ménesi, Rudolf; Pávó, Imre; László, Ferenc; Varga, Csaba

    2015-01-01

    Estrogen deficiency is one of the main causes of age-associated diseases in the cardiovascular system. Female Wistar rats were divided into four experimental groups: pharmacologically ovariectomized, surgically ovariectomized, and 24-month-old intact aging animals were compared with a control group. The activity and expression of heme oxygenases (HO) in the cardiac left ventricle, the concentrations of cardiac interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), the myeloperoxidase (MPO) activity in the cardiac left ventricle, and the effects of heme oxygenase blockade (by 24-hour and 1-hour pretreatment with tin-protoporphyrin IX, SnPP) on the epinephrine and phentolamine-induced electrocardiogram ST segment changes in vivo were investigated. The cardiac HO activity and the expression of HO-1 and HO-2 were significantly decreased in the aged rats and after ovariectomy. Estrogen depletion was accompanied by significant increases in the expression of IL-6 and TNF-α. The aged and ovariectomized animals exhibited a significantly elevated MPO activity and a significant ST segment depression. After pretreatment with SnPP augmented ST segment changes were determined. These findings demonstrate that the sensitivity to cardiac ischemia in estrogen depletion models is associated with suppression of the activity and expression of the HO system and increases in the secretion of proinflammatory cytokines and biomarkers. PMID:26064421

  7. 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.

  8. Mechanism of action and efficacy of RX-111, a thieno[2,3-c]pyridine derivative and small molecule inhibitor of protein interaction with glycosaminoglycans (SMIGs), in delayed-type hypersensitivity, TNBS-induced colitis and experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Harris, Nicholas; Koppel, Juraj; Zsila, Ferenc; Juhas, Stefan; Il'kova, Gabriela; Kogan, Faina Yurgenzon; Lahmy, Orly; Wildbaum, Gizi; Karin, Nathan; Zhuk, Regina; Gregor, Paul

    2016-04-01

    Elucidate the mechanism of action of the small molecule inhibitor of protein binding to glycosaminoglycans, RX-111 and assay its anti-inflammatory activity in animal models of inflammatory disease. The glycosaminoglycan, heparin, was used in the mechanism of action study of RX-111. Human T lymphocytes and umbilical vein endothelial cells were used to assay the in vitro activity of RX-111. Mouse and rat models of disease were used to assay the anti-inflammatory activity of RX-111 in vivo. Circular dichroism and UV/Vis absorption spectroscopy were used to study the binding of RX-111 to the glycosaminoglycan, heparin. T lymphocyte rolling on endothelial cells under shear flow was used to assay RX-111 activity in vitro. Delayed-type hypersensitivity (DTH) and tri-nitrobenzene sulfonic acid (TNBS)-induced colitis in mice and experimental autoimmune encephalomyelitis (EAE) in rats were used to assay anti-inflammatory activity of RX-111 in vivo. RX-111 was shown to bind directly to heparin. It inhibited leukocyte rolling on endothelial cells under shear flow and reduced inflammation in the mouse model of DTH. RX-111 was efficacious in the mouse model of inflammatory bowel disease, TNBS-induced colitis and the rat model of multiple sclerosis, EAE. RX-111 exercises its broad spectrum anti-inflammatory activity by a singular mechanism of action, inhibition of protein binding to the cell surface GAG, heparan sulfate. RX-111 and related thieno[2,3-c]pyridine derivatives are potential therapeutics for the treatment of inflammatory and autoimmune diseases.

  9. An arachidonic acid-enriched diet does not result in more colonic inflammation as compared with fish oil- or oleic acid-enriched diets in mice with experimental colitis

    NARCIS (Netherlands)

    Ramakers, Julian D.; Mensink, Ronald P.; Verstege, Marleen I.; te Velde, Anje A.; Plat, Jogchum

    2008-01-01

    Fish oils (FO) - rich in EPA and DHA - may protect against colitis development. Moreover, inflammatory bowel disease patients have elevated colonic arachidonic acid (AA) proportions. So far, effects of dietary AA v. FO on colitis have never been examined. We therefore designed three isoenergetic

  10. An adenosine A3 receptor agonist inhibits DSS-induced colitis in mice through modulation of the NF-κB signaling pathway

    Science.gov (United States)

    Ren, Tianhua; Tian, Ting; Feng, Xiao; Ye, Shicai; Wang, Hao; Wu, Weiyun; Qiu, Yumei; Yu, Caiyuan; He, Yanting; Zeng, Juncheng; Cen, Junwei; Zhou, Yu

    2015-01-01

    The role of the adenosine A3 receptor (A3AR) in experimental colitis is controversial. The A3AR agonist N6-(3-iodobenzyl)adenosine-5'-N-methyluronamide (IB-MECA) has been shown to have a clinical benefit, although studies in A3AR-deficient mice suggest a pro-inflammatory role. However, there are no studies on the effect of 2-Cl-IB-MECA and the molecular mechanism of action of A3AR in murine colitis models in vivo. Is it the same as that observed in vitro? The interaction between 2-CL-IB-MECA and A3AR in a murine colitis model and the signaling pathways associated with this interaction remain unclear. Here we demonstrate a role for the NF-κB signaling pathway and its effect on modifying the activity of proinflammatory factors in A3AR-mediated biological processes. Our results demonstrated that A3AR activation possessed marked effects on experimental colitis through the NF-κB signaling pathway. PMID:25762375

  11. Coenzyme Q10 Inhibits Th17 and STAT3 Signaling Pathways to Ameliorate Colitis in Mice.

    Science.gov (United States)

    Lee, Seon-Yeong; Lee, Seung Hoon; Yang, Eun-Ji; Kim, Jae-Kyung; Kim, Eun-Kyung; Jung, KyungAh; Jung, Hongsoon; Lee, Kyungjin; Lee, Han Hee; Lee, Bo-In; Park, Sung-Hwan; Shin, Dong Yun; Cho, Mi-La

    2017-09-01

    Coenzyme Q10 (CoQ10) is a powerful antioxidant substance synthesized in the body. The current study aimed to determine whether CoQ10 suppresses inflammation and inhibits p-STAT3 expression in an experimental colitis mouse model. The mice were orally fed with CoQ10 once a day for 13 days. Histological analysis of the colons was performed by immunohistochemistry. Expression of IL-17, FOXP3, p53, AMPK, and mTOR and activation of p-STAT3 and p-STAT5 in lymph node and spleen tissues were detected by confocal microscopy of stained tissue sections. The relative mRNA expression was measured with real-time PCR, and protein levels were examined by western blot. CoQ10 reduced the disease activity index score and the colon histological score. It also reduced inflammatory mediators in the colon and increased the colon length. The expression of IL-17 and p-STAT3 was decreased with CoQ10 treatment. In contrast, CoQ10 treatment increased the expression of p-AMPK and FOXP3. Expression of anti-inflammatory cytokines was shown to increase in colitis mice treated with CoQ10. These results suggested that CoQ10 may reduce the severity of colitis and suppress inflammation through the inhibition of p-STAT3 and IL-17. These results support the use of CoQ10 as a potential targeted therapy for the treatment of colitis.

  12. Arsenic and chromium in drinking water promote tumorigenesis in a mouse colitis-associated colorectal cancer model and the potential mechanism is ROS-mediated Wnt/β-catenin signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xin; Mandal, Ardhendu K. [Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536 (United States); Saito, Hiroshi [Department of Surgery and Physiology, Lucille P. Markey Cancer Center, University of Kentucky, Lexington, KY 40536 (United States); Pulliam, Joseph F.; Lee, Eun Y. [Pathology and Laboratory Medicine, University of Kentucky, Lexington, KY 40536 (United States); Ke, Zun-Ji; Lu, Jian; Ding, Songze [Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536 (United States); Li, Li [Department of Family Medicine, Case Western Reserve University, Cleveland, OH 44106 (United States); Shelton, Brent J.; Tucker, Thomas [Markey Cancer Control Program, University of Kentucky, Lexington, KY 40504 (United States); Evers, B. Mark [Department of Surgery and Physiology, Lucille P. Markey Cancer Center, University of Kentucky, Lexington, KY 40536 (United States); Zhang, Zhuo [Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536 (United States); Shi, Xianglin, E-mail: xshi5@uky.edu [Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536 (United States)

    2012-07-01

    Exposure to carcinogenic metals, such as trivalent arsenic [As(III)] and hexavalent chromium [Cr(VI)], through drinking water is a major global public health problem and is associated with various cancers. However, the mechanism of their carcinogenicity remains unclear. In this study, we used azoxymethane/dextran sodium sulfate (AOM/DSS)-induced mouse colitis-associated colorectal cancer model to investigate their tumorigenesis. Our results demonstrate that exposure to As(III) or Cr(VI), alone or in combination, together with AOM/DSS pretreatment has a promotion effect, increasing the colorectal tumor incidence, multiplicity, size, and grade, as well as cell inflammatory response. Two-dimensional differential gel electrophoresis coupled with mass spectrometry revealed that As(III) or Cr(VI) treatment alone significantly changed the density of proteins. The expression of β-catenin and phospho-GSK was increased by treatment of carcinogenic metals alone. Concomitantly, the expression of NADPH oxidase1 (NOX1) and the level of 8-OHdG were also increased by treatment of carcinogenic metals alone. Antioxidant enzymes, such as superoxide dismutase (SOD) and catalase, were decreased. Similarly, in an in vitro system, exposure of CRL-1807 to carcinogenic metals increased reactive oxygen species (ROS) generation, the expression of β-catenin, phospho-GSK, and NOX1. Inhibition of ROS generation by addition of SOD or catalase inhibited β-catenin expression and activity. Our study provides a new animal model to study the carcinogenicity of As(III) and Cr(VI) and suggests that As(III) and Cr(VI) promote colorectal cancer tumorigenesis, at least partly, through ROS-mediated Wnt/β-catenin signaling pathway. -- Highlights: ► Carcinogenic metals in drinking water promote colorectal tumor formation in vivo. ► Carcinogenic metals induce β-catenin activation in vivo and in vitro. ► ROS generation induced by carcinogenic metals mediated β-catenin activation.

  13. Reduced platelet-mediated and enhanced leukocyte-mediated fibrinolysis in experimentally induced diabetes in rats

    Energy Technology Data Exchange (ETDEWEB)

    Winocour, P.D.; Colwell, J.A.

    1985-05-01

    Studies of fibrinolytic activity in diabetes mellitus have produced conflicting results. This may be a result of methodologic insensitivity or of variable contributions of the different blood components to whole blood fibrinolysis. To explore these two possibilities, the authors used a sensitive solid-phase radiometric assay to examine the fibrinolytic activity of whole blood, platelet-rich plasma, leukocytes, and platelet- and leukocyte-poor plasma prepared from control rats and rats with streptozocin-induced diabetes at various times after induction of diabetes. Fibrinolytic activity of whole blood from diabetic rats after 7 days was significantly reduced, and remained reduced after longer durations of diabetes up to 28 days. Platelet-rich plasma from diabetic rats had decreased fibrinolytic activity, which followed the same time course of changes as in whole blood. The platelet contribution to whole blood fibrinolysis was further reduced in vivo after 14 days of diabetes by a reduced whole blood platelet count. In contrast, fibrinolytic activity of leukocytes from diabetic rats became enhanced after 7 days of diabetes. After 49 days of diabetes, the whole blood leukocyte count was reduced, and in vivo would offset the enhanced activity. Plasma fibrinolytic activity was small compared with that of whole blood and was unaltered in diabetic rats. The authors conclude that altered platelet function contributes to decreased fibrinolytic activity of whole blood in diabetic rats, and that this may be partially offset by enhanced leukocyte-mediated fibrinolysis.

  14. Id1 Deficiency Protects against Tumor Formation in Apc(Min/+) Mice but Not in a Mouse Model of Colitis-Associated Colon Cancer.

    Science.gov (United States)

    Zhang, Ning; Subbaramaiah, Kotha; Yantiss, Rhonda K; Zhou, Xi Kathy; Chin, Yvette; Benezra, Robert; Dannenberg, Andrew J

    2015-04-01

    Different mechanisms contribute to the development of sporadic, hereditary and colitis-associated colorectal cancer. Inhibitor of DNA binding/differentiation (Id) proteins act as dominant-negative antagonists of basic helix-loop-helix transcription factors. Id1 is a promising target for cancer therapy, but little is known about its role in the development of colon cancer. We used immunohistochemistry to demonstrate that Id1 is overexpressed in human colorectal adenomas and carcinomas, whether sporadic or syndromic. Furthermore, elevated Id1 levels were found in dysplasia and colon cancer arising in patients with inflammatory bowel disease. Because levels of PGE2 are also elevated in both colitis and colorectal neoplasia, we determined whether PGE2 could induce Id1. PGE2 via EP4 stimulated protein kinase A activity resulting in enhanced pCREB-mediated Id1 transcription in human colonocytes. To determine the role of Id1 in carcinogenesis, two mouse models were used. Consistent with the findings in humans, Id1 was overexpressed in tumors arising in both Apc(Min) (/+) mice, a model of familial adenomatous polyposis, and in experimental colitis-associated colorectal neoplasia. Id1 deficiency led to significant decrease in the number of intestinal tumors in Apc(Min) (/+) mice and prolonged survival. In contrast, Id1 deficiency did not affect the number or size of tumors in the model of colitis-associated colorectal neoplasia, likely due to exacerbation of colitis associated with Id1 loss. Collectively, these results suggest that Id1 plays a role in gastrointestinal carcinogenesis. Our findings also highlight the need for different strategies to reduce the risk of colitis-associated colorectal cancer compared with sporadic or hereditary colorectal cancer. ©2015 American Association for Cancer Research.

  15. Temporal and spatial analysis of clinical and molecular parameters in dextran sodium sulfate induced colitis.

    Directory of Open Access Journals (Sweden)

    Yutao Yan

    Full Text Available BACKGROUND: Inflammatory bowel diseases (IBD, including mainly ulcerative colitis (UC and Crohn's disease (CD, are inflammatory disorders of the gastrointestinal tract caused by an interplay of genetic and environmental factors. Murine colitis model induced by Dextran Sulfate Sodium (DSS is an animal model of IBD that is commonly used to address the pathogenesis of IBD as well as to test efficacy of therapies. In this study we systematically analyzed clinical parameters, histological changes, intestinal barrier properties and cytokine profile during the colitic and recovery phase. METHODS: C57BL/6 mice were administered with 3.5% of DSS in drinking water for various times. Clinical and histological features were determined using standard criteria. Myeloperoxidase (MPO activity, transepithelial permeability and proinflammatory mediators were determined in whole colon or proximal and distal parts of colon. RESULTS: As expected after administration of DSS, mice manifest loss of body weight, shortening of colon length and bloody feces. Histological manifestations included shortening and loss of crypts, infiltration of lymphocytes and neutrophil, symptoms attenuated after DSS withdrawal. The MPO value, as inflammation indicator, also increases significantly at all periods of DSS treatment, and even after DSS withdrawal, it still held at very high levels. Trans-mucosal permeability increased during DSS treatment, but recovered to almost control level after DSS withdrawal. The production of proinflammatory mediators by colonic mucosa were enhanced during DSS treatment, and then recovered to pre-treated level after DSS withdrawal. Finally, enhanced expression of proinflammatory mediators also revealed a different profile feature in proximal and distal parts of the colon. CONCLUSION: Experimental colitis induced by DSS is a good animal model to study the mechanisms underlying the pathogenesis and intervention against IBD, especially UC.

  16. Protective effect of Dillenia indica L. on acetic acid induced colitis in mice.

    Science.gov (United States)

    Somani, S J; Badgujar, L B; Sutariya, B K; Saraf, M N

    2014-09-01

    The inflammatory bowel disease (IBD) is an idiopathic, immune mediated and chronic inflammation of the intestine. The study aimed to elucidate the ameliorative effect of methanolic extract of Dillenia indica (DIME), hexane fraction (HFDI) and chloroform fraction (CFDI) of Dillenia indica in acetic acid induced experimental colitis in mice. Macroscopic score, colon weight, colonic catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), myeloperoxidase (MPO), malondialdehyde (MDA), tumor necrosis factor (TNF-alpha), and histological changes were recorded after the treatment regimen of 7 days. Intra-rectal instillation of acetic acid caused enhanced macroscopic score, colon weight, colonic MPO, MDA, and TNF-alpha level. It caused significant decreased level of CAT, SOD and GSH. DIME (800 mg/kg), HFDI (200 mg/kg) and CFDI (200 mg/kg) treatment exhibited significant effect in lowering macroscopic score, colon weight, MPO, MDA, TNF-alpha levels and elevation of CAT, GSH and SOD levels. The results suggest that D. indica has ameliorating effects on experimental colitis by inhibiting the proinflammatory mediators like TNF-alpha production.

  17. Teen Guide: Dealing with Crohn's & Colitis

    Science.gov (United States)

    ... Colitis Go Back Teen Guide: Dealing with Crohn’s & Colitis Email Print + Share Your doctor has just told ... types of IBD are Crohn’s disease and ulcerative colitis . The GI tract is responsible for digestion of ...

  18. Reconstitution of Scid mice with CD4+CD25- T cells leads to rapid colitis: an improved model for pharmacologic testing

    DEFF Research Database (Denmark)

    Kjellev, Stine; Lundsgaard, Dorthe; Poulsen, Steen Seier

    2006-01-01

    Improved experimental colitis models are needed for evaluation of treatment strategies for IBD. Most current models either lack resemblance to IBD, are complicated to establish, or the colitis occurs slowly and inconsistently. Our aim was to characterize the course of colitis in C.B-17 Scid mice...

  19. Pseudomembranous colitis in cystic fibrosis.

    Science.gov (United States)

    Nagakumar, Prasad

    2013-05-01

    Cystic fibrosis (CF) patients may require frequent courses of antibiotics and repeated hospital admissions. Although children with CF have high carriage rate for C.difficile, they rarely develop colitis. Pseudomembranous colitis is more common in adult post lung transplant CF patients. Although rare, paseudomembranous colitis should be considered in CF patients presenting with abdominal symptoms even in the absence of diarrhoea. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Immunohistochemical assessment of mucosal cytokine profile in acetic acid experimental colitis Avaliação imunohistoquímica do perfil citocínico da mucosa colônica em colite experimental induzida por ácido acético

    Directory of Open Access Journals (Sweden)

    Pedro L. Bertevello

    2005-08-01

    Full Text Available Experimental colitis induced by acetic acid has been used extensively as a model for intestinal inflammatory disease. Colonic tissue lesions of intestinal inflammatory disease patients seem to be related to the increased local production of pro-inflammatory cytokines (IL-1, IL-6, TNF-alpha, and IFN-gamma. PURPOSE: To assess the cytokine expression pattern identified through immunohistochemistry in colonic mucosa after experimental colitis induced by acetic acid and establish the relationship between this pattern and the presence of macroscopic lesions. MATERIALS AND METHODS: Adult male Wistar rats (n = 39 were divided at random into 4 groups: NC45 and NC24 (control without colitis; sacrificed at 45 minutes and 24 hours, respectively; and WC45 and WC24 (with experimental colitis induced by acetic acid; sacrificed at 45 minutes and 24 hours, respectively. Macroscopic and microscopic alterations in colonic tissue were evaluated, and cytokine expression was assessed through immunohistochemistry. RESULTS: After 24 hours, IL-1 expression was greater in the groups with colitis when compared to the groups without colitis. IL-4 expression was higher in the WC45 group. There was an increase in both INF-gamma and IL-6 related to the presence of necrosis of the colonic mucosa in the groups with colitis for both periods evaluated. CONCLUSION: The immunohistochemical technique was efficient for the analysis of various cytokine expressions in the colonic tissue. There was an increase in the IL-1 pro-inflammatory cytokines as well as in IL-6 and IFN-gamma associated with the presence of colonic necrosis. Experimental colitis induced by acetic acid is a useful model for the development of studies assessing the role of cytokines in the inflammation of mucosa as well as anti-cytokine therapies.O modelo de colite experimental induzida por ácido acético (CEAA vem sendo extensamente utilizado em estudos sobre doenças inflamatórias intestinais (DII. Lesões no

  1. Chromofungin Ameliorates the Progression of Colitis by Regulating Alternatively Activated Macrophages

    Directory of Open Access Journals (Sweden)

    Nour Eissa

    2017-09-01

    Full Text Available Ulcerative colitis (UC is characterized by a functional dysregulation of alternatively activated macrophage (AAM and intestinal epithelial cells (IECs homeostasis. Chromogranin-A (CHGA secreted by neuroendocrine cells is implicated in intestinal inflammation and immune dysregulation. CHGA undergoes proteolytic processing to generate CHGA-derived peptides. Chromofungin (CHR: CHGA47–66 is a short CHGA-derived peptide encoded by CHGA Exon-IV and is involved in innate immune regulation, but the basis is poorly investigated. We investigated the expression of CHR in colonic tissue of patients with active UC and assessed the effects of the CHR in dextran sulfate sodium (DSS colitis in mice and on macrophages and human colonic epithelial cells. We found that mRNA expression of CHR correlated positively with mRNA levels of AAM markers and gene expression of tight junction (TJ proteins and negatively with mRNA levels of interleukin (IL-8, IL-18, and collagen in patients with active UC. Moreover, AAM markers correlated positively with gene expression of TJ proteins and negatively with IL-8, IL-18, and collagen gene expression. Experimentally, intracolonic administration of CHR protected against DSS-induced colitis by priming macrophages into AAM, reducing colonic collagen deposition, and maintaining IECs homeostasis. This effect was associated with a significant increase of AAM markers, reduction of colonic IL-18 release and conservation of gene expression of TJ proteins. In vitro, CHR enhanced AAM polarization and increased the production of anti-inflammatory mediators. CHR-treated AAM conditioned medium increased Caco-2 cell migration, viability, proliferation, and mRNA levels of TJ proteins, and decreased oxidative stress-induced apoptosis and proinflammatory cytokines release. Direct CHR treatments had the same effect. In conclusion, CHR treatment reduces the severity of colitis and the inflammatory process via enhancing AAM functions and maintaining

  2. Bifidobacterium infantis attenuates colitis by regulating T cell subset responses

    Science.gov (United States)

    Zuo, Li; Yuan, Kai-Tao; Yu, Li; Meng, Qing-Hong; Chung, Peter Chee-Keung; Yang, Ding-Hua

    2014-01-01

    AIM: to investigate the effect of Bifidobacterium infantis (B. infantis) on the T cell subsets and in attenuating the severity of experimental colitis in mice. METHODS: Normal BALB/c mice were fed different doses of B. infantis for 3 wk, and T cell subsets and related cytokine profiles in mesenteric lymph nodes (MLNs) were detected by flow cytometry and real-time RT-PCR. Colitis was induced by administration of trinitrobenzene sulfonic acid (TNBS) in mice. Before colitis induction, mice were fed high dose B. infantis for 3 wk. Cytokine profiles in MLNs and histological changes of colonic tissue were examined 6 d after colitis induction. RESULTS: No significant change in cytokine profiles was observed in normal mice fed low dose B. infantis. However, Th1-related cytokines (IL-2, IFN-γ, IL-12p40), Th17-related transcription factor and cytokines (RORγt, IL-21, IL-23), regulatory T cell (Treg)-related transcription factor and cytokines (Foxp3, IL-10) were increased in normal mice fed high dose B. infantis. Furthermore, flow cytometry assay showed B. infantis increased the numbers of CD4+Foxp3+ Tregs and Th17 cells in MLNs. Colitis was successfully induced by TNBS in mice, characterized by colonic inflammation and aberrant Th1 and Th17 responses. Feeding high dose B. infantis for 3 wk before colitis induction decreased the inflammatory cell infiltration and goblet cell depletion and restored the intestinal epithelium. In addition, B. infantis feeding reduced Th1-related cytokines (T-bet, IL-2 and IFN-γ) and Th17-related cytokines (IL-12p40, RORγt, IL-17A, IL-21 and IL-23), and increased Treg-related molecules (Foxp3, IL-10 and TGF-β) in colitis mice. CONCLUSION: B. infantis effectively attenuates TNBS-induced colitis by decreasing Th1 and Th17 responses and increasing Foxp3+ Treg response in the colonic mucosa. PMID:25561798

  3. Animal Models of Colitis-Associated Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Manasa Kanneganti

    2011-01-01

    Full Text Available Inflammatory bowel disease (IBD is a group of chronic inflammatory disorders that affect individuals throughout life. Although the etiology and pathogenesis of IBD are largely unknown, studies with animal models of colitis indicate that dysregulation of host/microbial interactions are requisite for the development of IBD. Patients with long-standing IBD have an increased risk for developing colitis-associated cancer (CAC, especially 10 years after the initial diagnosis of colitis, although the absolute number of CAC cases is relatively small. The cancer risk seems to be not directly related to disease activity, but is related to disease duration/extent, complication of primary sclerosing cholangitis, and family history of colon cancer. In particular, high levels and continuous production of inflammatory mediators, including cytokines and chemokines, by colonic epithelial cells (CECs and immune cells in lamina propria may be strongly associated with the pathogenesis of CAC. In this article, we have summarized animal models of CAC and have reviewed the cellular and molecular mechanisms underlining the development of carcinogenic changes in CECs secondary to the chronic inflammatory conditions in the intestine. It may provide us some clues in developing a new class of therapeutic agents for the treatment of IBD and CAC in the near future.

  4. Microscopic colitis. A review.

    Science.gov (United States)

    Brown, William R; Tayal, Shalini

    2013-06-01

    Microscopic colitis (MC) is characterized by a triad of watery diarrhea, usually normal colonoscopic findings and typical microscopic findings. Two distinct histological forms of MC have been defined: lymphocytic colitis and collagenous colitis, but overlapping features may be present. The incidence of MC appears to be rising and in some countries it may account for as many as 10-20% of patients with non-bloody watery diarrhea. The cause of MC remains unknown and is likely to be multifactorial. The pathogenesis is poorly defined, and numerous immunological abnormalities have been reported. MC is commonly associated with autoimmune diseases including celiac disease. Use of various medications, most notably non-steroidal anti-inflammatory agents and proton pump inhibitors, have been etiologically implicated but not firmly established as causative. In imperfect trials several agents have been reported to be effective in the treatment of MC; budesonide is the best studied and evidence supporting its effectiveness is the most persuasive. In cases of otherwise unexplained watery, non-bloody diarrhea, MC should be considered and colonic biopsied specimens should be taken of normal-appearing mucosa. © 2013 The Authors. Journal of Digestive Diseases © 2013 Wiley Publishing Asia Pty Ltd and Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine.

  5. Simultaneous Determination of Three Furanocoumarins by UPLC/MS/MS: Application to Pharmacokinetic Study of Angelica dahurica Radix after Oral Administration to Normal and Experimental Colitis-Induced Rats.

    Science.gov (United States)

    Hwang, Youn-Hwan; Yang, Hye Jin; Ma, Jin Yeul

    2017-03-07

    In traditional oriental medicine, Angelica dahurica Radix (ADR) is used in the treatment of gastrointestinal, respiratory, neuromuscular, and dermal disorders. We evaluated the pharmacokinetic profiles of oxypeucedanin, imperatorin, and isoimperatorin, major active ingredients of ADR, in normal and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis rats. A rapid, sensitive, and validated UPLC/MS/MS method was established for evaluating the pharmacokinetics of three furanocoumarins. After oral administration of ADR (0.5 and 1.0 g/kg), blood samples were collected periodically from the tail vein. In colitis rats, the time to reach the peak concentration (Tmax) of imperatorin and isoimperatorin was significantly delayed (p colitis-related changes in the drug-absorption phase. Therefore, the prescription and use of ADR in colitis patients should receive more attention.

  6. Theoretical and Experimental Studies of Polymer Adsorption and Polymer Mediated Interactions

    OpenAIRE

    Xie, Fei

    2016-01-01

    Polyelectrolyte adsorption and polymer mediated interactions in different colloidal polymer systems have been studied in this work. Theoretical methods and experimental techniques are combined, in order to obtain more general reliable results, as well as a deep understanding of the molecular mechanisms that are responsible for the observed behaviors. Two different types of highly charged cationic polyions have been used to explore the adsorption onto oppositely charged surfaces. The adsorptio...

  7. Recurrent colitis following antibiotic-associated pseudomembranous colitis.

    Science.gov (United States)

    Davies, J.; Beck, E.

    1981-01-01

    A patient who developed severe pseudomembranous colitis following clindamycin therapy, and who went on to have recurrent attacks of non-specific colitis, histologically confirmed over the following 19 months, is described. Images Fig. 1 Fig. 2 Fig. 3 PMID:7329901

  8. Successful treatment of ulcerative colitis with leukocytapheresis using non-woven polyester filter.

    Science.gov (United States)

    Sakata, Hiromi; Kawamura, Naoyuki; Horie, Takashi; Ohizumi, Hiroko; Tamaki, Tohru; Kukita, Kazutaka; Meguro, Jun-ichi; Yonekawa, Motoki; Saitoh, Masao; Kawamura, Akio

    2003-12-01

    Ulcerative colitis is a chronic inflammatory disease of the rectum and colon. Although the pathogenesis of ulcerative colitis is not fully elucidated, cell-mediated immunity plays an important role in disease pathogenesis. Leukocytapheresis is a newly emerging therapy to eliminate activated leukocyte from systemic circulation. We have studied the effects of leukocytapheresis on patients with ulcerative colitis who had failed to respond to conventional therapy. A total of 51 patients with ulcerative colitis were treated with apheresis using a non-woven polyester fiber filter (Finecell, Asahi Medical Co.,Tokyo, Japan) originally developed as a microcoagulation elimination filter for massive transfusion. Of the 51 patients, 33 (64.7%) achieved clinical remission manifested by clinical activity and colonoscopic findings without any adverse effects. This result suggested that leukocytapheresis using Finecell might serve as an alternative therapy for ulcerative colitis as other leukocytapheresis using centrifugation or column.

  9. Segmental Colitis Complicating Diverticular Disease

    Directory of Open Access Journals (Sweden)

    Guido Ma Van Rosendaal

    1996-01-01

    Full Text Available Two cases of idiopathic colitis affecting the sigmoid colon in elderly patients with underlying diverticulosis are presented. Segmental resection has permitted close review of the histopathology in this syndrome which demonstrates considerable similarity to changes seen in idiopathic ulcerative colitis. The reported experience with this syndrome and its clinical features are reviewed.

  10. Pseudomembranous colitis following cephradine prophylaxis.

    Science.gov (United States)

    Sankarankutty, M.; McGeorge, D.; Galasko, C. S.

    1982-01-01

    Two patients on antibiotic prophylaxis with cephradine after orthopaedic implant surgery developed pseudomembranous colitis. Routine administration of antibiotics after such surgery is the policy at many centres. Development of diarrhoea in these patients should be viewed seriously lest this condition is overlooked. Despite recent advances, pseudomembranous colitis can still have a fatal outcome. PMID:7170277

  11. Suppression of experimental autoimmune encephalomyelitis by ultraviolet light is not mediated by isomerization of urocanic acid.

    Science.gov (United States)

    Irving, Amy A; Marling, Steven J; Plum, Lori A; DeLuca, Hector F

    2017-01-05

    Ultraviolet B irradiation confers strong resistance against experimental autoimmune encephalomyelitis, a model of multiple sclerosis. This protection by ultraviolet B is independent of vitamin D production but causes isomerization of urocanic acid, a naturally occurring immunosuppressant. To determine whether UCA isomerization from trans to cis is responsible for the protection against experimental autoimmune encephalomyelitis afforded by ultraviolet B, trans- or cis-urocanic acid was administered to animals and their disease progression was monitored. Disease incidence was reduced by 74% in animals exposed to ultraviolet B, and skin cis-urocanic acid levels increased greater than 30%. However, increasing skin cis-urocanic acid levels independent of ultraviolet B was unable to alter disease onset or progression. It is unlikely that urocanic acid isomerization is responsible for the ultraviolet B-mediated suppression of experimental autoimmune encephalomyelitis. Additional work is needed to investigate alternative mechanisms by which UVB suppresses disease.

  12. Protective effect of apocynin in a mouse model of chemically-induced colitis.

    Science.gov (United States)

    Marín, Marta; Giner, Rosa María; Ríos, José-Luis; Recio, María del Carmen

    2013-10-01

    Apocynin, a constituent of Picrorhiza kurroa, successfully inhibits NADPH oxidase and shows promise as an anti-inflammatory drug. Now, we report anti-inflammatory effects of apocynin in an experimental colitis model induced by dextran sulfate sodium as well as the effects on the mediators involved in this process. Apocynin reduced the colitis induced in mice by administration of 5 % dextran sulfate sodium during 7 days. Mice were fed a control diet or a diet supplemented with 2 % of apocynin or 2 % of rutin. Sulfasalazine (50 mg/kg, p. o.) was used as a positive control. Treatment with apocynin and rutin ameliorated the course of colonic inflammation with results similar to those of the reference drug, as could be seen by reductions in the disease activity index scores and colon length. NO and PGE2 production as well as the iNOS and COX-2 expression were reduced by apocynin and rutin. Moreover, the activation of NF-κB p65 as well as STAT3 in dextran sulfate sodium-treated colon tissues was significantly reduced by apocynin. These results are promising for further experimental studies on treating gastrointestinal diseases and on the potential protective effects of apocynin. Georg Thieme Verlag KG Stuttgart · New York.

  13. Paradoxical regulation of ChAT and nNOS expression in animal models of Crohn's colitis and ulcerative colitis.

    Science.gov (United States)

    Winston, John H; Li, Qingjie; Sarna, Sushil K

    2013-08-15

    Morphological and functional changes in the enteric nervous system (ENS) have been reported in inflammatory bowel disease. We examined the effects of inflammation on the expression of choline acetyltransferase (ChAT) and nNOS in the muscularis externae of two models of colonic inflammation, trinitrobenzene sulfonic acid (TNBS)-induced colitis, which models Crohn's disease-like inflammation, and DSS-induced colitis, which models ulcerative Colitis-like inflammation. In TNBS colitis, we observed significant decline in ChAT, nNOS, and protein gene product (PGP) 9.5 protein and mRNA levels. In DSS colitis, ChAT and PGP9.5 were significantly upregulated while nNOS levels did not change. The nNOS dimer-to-monomer ratio decreased significantly in DSS- but not in TNBS-induced colitis. No differences were observed in the percentage of either ChAT (31 vs. 33%)- or nNOS (37 vs. 41%)-immunopositive neurons per ganglia or the mean number of neurons per ganglia (55 ± 5 vs. 59 ± 5, P > 0.05). Incubation of the distal colon muscularis externae in vitro with different types of inflammatory mediators showed that cytokines decreased ChAT and nNOS expression, whereas H₂O₂, a component of oxidative stress, increased their expression. NF-κB inhibitor MG-132 did not prevent the IL-1β-induced decline in either ChAT or nNOS expression. These findings showed that TNBS- and DSS-induced inflammation differentially regulates the expression of two critical proteins expressed in the colonic myenteric neurons. These differences are likely due to the exposure of the myenteric plexus neurons to different combinations of Th1-type inflammatory mediators and H₂O₂ in each model.

  14. [Colitis associated with C. difficile].

    Science.gov (United States)

    Mironov, I L; Ratnikova, L I; Pirogov, D V; Mil'chenko, I B

    2014-01-01

    Pseudomembranous colitis (PMC), is characterized by acute onset, severe diarrhea, hypovolemic shock, toxic expansion of colon perforation, thrombus syndrome and without treatment in some cases leading to death of the patient. The paper describes a clinical case of pseudomembranous colitis in patients 35 years that developed on the background of the massive antibiotic therapy. The diagnosis was made only at autopsy. This case is unique, and dictates the need to inform doctors of practical health care of the complications of antibiotic therapy, such as pseudomembranous colitis.

  15. Computer-mediated communication and interpersonal attraction: an experimental test of two explanatory hypotheses.

    Science.gov (United States)

    Antheunis, Marjolijn L; Valkenburg, Patti M; Peter, Jochen

    2007-12-01

    The aims of this study were (a) to investigate the influence of computer-mediated communication (CMC) on interpersonal attraction and (b) to examine two underlying processes in the CMC-interpersonal attraction relationship. We identified two variables that may mediate the influence of CMC on interpersonal attraction: self-disclosure and direct questioning. Focusing on these potential mediating variables, we tested two explanatory hypotheses: the CMC-induced direct questioning hypothesis and the CMC-induced self-disclosure hypothesis. Eighty-one cross-sex dyads were randomly assigned to one of three experimental conditions: text-only CMC, visual CMC, and face-to-face communication. We did not find a direct effect of CMC on interpersonal attraction. However, we did find two positive indirect effects of text-only CMC on interpersonal attraction: text-only CMC stimulated both self-disclosure and direct questioning, both of which in turn enhanced interpersonal attraction. Results are discussed in light of uncertainty reduction theory and CMC theories.

  16. Critical Role of PepT1 in Promoting Colitis-Associated Cancer and Therapeutic Benefits of the Anti-inflammatory PepT1-Mediated Tripeptide KPV in a Murine ModelSummary

    Directory of Open Access Journals (Sweden)

    Emilie Viennois

    2016-05-01

    Full Text Available Background & Aims: The human intestinal peptide transporter 1 (hPepT1, is expressed in the small intestine at low levels in the healthy colon and up-regulated during inflammatory bowel disease. hPepT1 plays a role in mouse colitis and human studies have shown that chronic intestinal inflammation leads to colorectal cancer (colitis-associated cancer; CAC. Hence, we assessed here the role of PepT1 in CAC. Methods: Mice with hPepT1 overexpression in intestinal epithelial cells (transgenic [TG] or PepT1 (PepT1-knockout [KO] deletion were used and CAC was induced by azoxymethane/dextran sodium sulfate. Results: TG mice had larger tumor sizes, increased tumor burdens, and increased intestinal inflammation compared with wild-type (WT mice. Conversely, tumor number and size and intestinal inflammation were decreased significantly in PepT1-KO mice. Proliferating crypt cells were increased in TG mice and decreased in PepT1-KO mice. Analysis of human colonic biopsy specimens showed increased expression of PepT1 in patients with colorectal cancer, suggesting that PepT1 might be targeted for the treatment of CAC. The use of an anti-inflammatory tripeptide Lys-Pro-Val (KPV transported by PepT1 was able to prevent carcinogenesis in WT mice. When administered to PepT1-KO mice, KPV did not trigger any of the inhibitory effect on tumorigenesis observed in WT mice. Conclusions: The observations that PepT1 was highly expressed in human colorectal tumor and that its overexpression and deletion in mice increased and decreased colitis-associated tumorigenesis, respectively, suggest that PepT1 is a potential therapeutic target for the treatment of colitis-associated tumorigenesis. Keywords: Colitis-Associated Cancer, Intestinal Inflammation, PepT1, KPV Peptide

  17. Crohn's & Colitis Foundation of America

    Science.gov (United States)

    ... to enjoy the full interactive experience. Crohn's & Colitis Foundation of America Find a Doctor Find a support ... Dating & Relationships Diagnosis & Testing Diet & Nutrition Disease Basics Finances Flares Health Insurance Medication Ostomy Patient Rights Pregnancy ...

  18. [Pseudomembranous colitis: pathogenesis, prevention, treatment].

    Science.gov (United States)

    Zakharova, N V; Fil', T S

    2013-01-01

    The article reviews a pathogenesis of Pseudomembranous colitis. Questions of prevention and treatment of Clostridium difficile--associated diarrhea are shown by the Evidence-based medicine. There is an accent on the rational prescription of antibiotics.

  19. IL-9 antibody injection suppresses the inflammation in colitis mice

    Energy Technology Data Exchange (ETDEWEB)

    Yuan, Aping [Laboratory of Molecular Cell Biology, Department of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Ås (Norway); Research Group of Gastrointestinal Diseases, The Second Affiliated Hospital of Zhengzhou University, Henan (China); Yang, Hang; Qi, Haili; Cui, Jing; Hua, Wei; Li, Can; Pang, Zhigang; Zheng, Wei [Research Group of Gastrointestinal Diseases, The Second Affiliated Hospital of Zhengzhou University, Henan (China); Cui, Guanglin, E-mail: guanglin.cui@yahoo.com [Research Group of Gastrointestinal Diseases, The Second Affiliated Hospital of Zhengzhou University, Henan (China); Faculty of Health, Nord University at Levanger (Norway)

    2015-12-25

    Diverse T help (Th) cells play a crucial role in the processing and maintaining of chronic inflammation as seen in ulcerative colitis (UC). Th9, a novel subset of Th cells that primarily produces interleukin (IL)-9, has recently been associated with the development of inflammatory diseases. In this study, we evaluated the presentation of Th9 cells in inflamed tissues of human and experimental mouse UC, and examined the therapeutic efficiency of anti Th9 cytokine IL-9 in the experimental mouse UC. Using immunohistochemistry (IHC), we evaluated the presentation of Th9 cells labelled by transcriptional factor PU.1 in both human and dextran sulfate sodium (DSS) induced mouse colitis biopsies. The results showed that increased PU.1 positive Th9 cells were mainly located in the lamina propria in relative with the controls, intraepithelial Th9 cells can also be observed but at low density. Double IHCs revealed that most of PU.1 positive cells were CD3 positive lymphocytes in human UC specimens. Anti-IL-9 antibody injection for 2 weeks reduced the severity of inflammation in DSS induced colitis mice. Our results suggest that The Th9/IL-9 is involved in the pathogenesis of UC. - Highlights: • The density of novel PU.1 positive Th9 cells is significantly increased in both human and mouse colitis tissues. • PU.1 positive Th9 cells are predominately located in the inflamed lamina propria in both human and mouse colitis tissues. • Blocking of Th9 cytokine IL-9 by antibody injection suppresses the severity of inflammation in the bowel in colitis mice. • Novel Th9 cells contribute to the pathogenesis of UC.

  20. 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)....

  1. Microscopic colitis: a concise review.

    Science.gov (United States)

    Zippi, M; Marcheggiano, A; Crispino, P; Occhigrossi, G; Severi, C

    2010-01-01

    Microscopic colitis is an increasingly common cause of chronic watery diarrhoea, and often a causes of abdominal pain of unknown origins. The increase of interest for this clinical entity is due to a misdiagnosis of any symptoms that have been frequently attributed to diarrhea-predominant irritable bowel syndrome, often for many years before diagnosis. Presumably, most estimates of incidence and prevalence understate the true frequency of microscopic colitis for this reason. The aim of this paper is to evaluate the importance of microscopic colitis as cause of chronic non bloody diarrhoea, on the basis of literature review. These kind of colitis are characterized by normal colonic mucosa at endoscopy or barium enema but with increased inflammation in colonic biopsies. Microscopic colitis consists of two main subtypes, collagenous colitis and lymphocytic colitis, distinguished by the presence of absence of a thickened subepithelial collagen band. Several models of pathogenesis has been proposed but no convincing mechanism has been identified, although is difficult to characterize this clinical entity as an independent phenomenon or a simple manifestation or related factors active to induce microscopic changing in the colonic mucosa. A rational approach to therapy does not exist and was conduct with several types of drugs after the exclusion of other causes, commonly characterized by this symptoms and the definitive histological assessment in the biopsies specimens. In the majority of cases this condition tends to follow a self-limited course but potentially can assume the characteristics of relapsing course with the necessity to a chronic therapy. Several long-term follow-up studies excluded a possible progression to neoplastic malignancies of microscopic colitis.

  2. [MICROSCOPIC COLITIS: THE CLINICAL CASE].

    Science.gov (United States)

    Kulygina, Y A; Skalinskaya, M I; Ageeva, T A

    2015-01-01

    During past years incidence and prevalence of microscopic colitis (MC) have increased, that is possible caused to the improvement of knowledge of doctors about the disease. This article contain modern views on epidemiology, diagnostic and variant of microscopic colitis treatment. A typical clinical picture of MC in the form of recurrent a watery diarrhea, with the absence of pathologic changes at roentgenologic and endoscopic investigations is described with the example of a clinical case.

  3. Ciclosporin and refractory colitis.

    Science.gov (United States)

    Hawthorne, A Barney

    2003-03-01

    Intravenous ciclosporin 4 mg/kg daily is rapidly effective as a salvage therapy for patients with refractory colitis, who would otherwise face colectomy, but its use is controversial because of risk of toxicity, and long-term failure rate. Opportunistic infections remain a serious concern, with a number of reports of death related to ciclosporin. Renal and neurotoxicity are also well-recognized. The drug should not be continued for more than 3-6 months and its main role is as a bridge to azathioprine or 6-mercaptopurine. Risks of toxicity can be reduced by using lower doses (2 mg/kg/day intravenously), by oral microemulsion ciclosporin, or by monotherapy without corticosteroids. Preliminary evidence shows good response rates, but further studies are needed to confirm optimal use of this potent, but hazardous, therapy.

  4. Divergent Roles of Interferon-γ and Innate Lymphoid Cells in Innate and Adaptive Immune Cell-Mediated Intestinal Inflammation.

    Science.gov (United States)

    Brasseit, Jennifer; Kwong Chung, Cheong K C; Noti, Mario; Zysset, Daniel; Hoheisel-Dickgreber, Nina; Genitsch, Vera; Corazza, Nadia; Mueller, Christoph

    2018-01-01

    Aberrant interferon gamma (IFNγ) expression is associated with the pathogenesis of numerous autoimmune- and inflammatory disorders, including inflammatory bowel diseases (IBD). However, the requirement of IFNγ for the pathogenesis of chronic intestinal inflammation remains controversial. The aim of this study was thus to investigate the role of IFNγ in experimental mouse models of innate and adaptive immune cell-mediated intestinal inflammation using genetically and microbiota-stabilized hosts. While we find that IFNγ drives acute intestinal inflammation in the anti-CD40 colitis model in an innate lymphoid cell (ILC)-dependent manner, IFNγ secreted by both transferred CD4 T cells and/or cells of the lymphopenic Rag1 -/- recipient mice was dispensable for CD4 T cell-mediated colitis. In the absence of IFNγ, intestinal inflammation in CD4 T cell recipient mice was associated with enhanced IL17 responses; consequently, targeting IL17 signaling in IFNγ-deficient mice reduced T cell-mediated colitis. Intriguingly, in contrast to the anti-CD40 model of colitis, depletion of ILC in the Rag1 -/- recipients of colitogenic CD4 T cells did not prevent induction of colonic inflammation. Together, our findings demonstrate that IFNγ represents an essential, or a redundant, pro-inflammatory cytokine for the induction of intestinal inflammation, depending on the experimental mouse model used and on the nature of the critical disease inducing immune cell populations involved.

  5. Efectos de un preparado probiótico en un modelo de colitis experimental crónica en ratones, inducida por la ingesta de dextrano sulfato sódico (DSS

    Directory of Open Access Journals (Sweden)

    S Bolívar González

    2015-01-01

    Conclusión: La administración del preparado probiótico, previene o retrasa los signos externos de la colitis, así como los niveles proteicos y génicos de marcadores inflamatorios asociados a ella.

  6. Mediatization

    DEFF Research Database (Denmark)

    Hjarvard, Stig

    2017-01-01

    Mediatization research shares media effects studies' ambition of answering the difficult questions with regard to whether and how media matter and influence contemporary culture and society. The two approaches nevertheless differ fundamentally in that mediatization research seeks answers...... to these general questions by distinguishing between two concepts: mediation and mediatization. The media effects tradition generally considers the effects of the media to be a result of individuals being exposed to media content, i.e. effects are seen as an outcome of mediated communication. Mediatization....... From the perspective of mediatization research, the most important effect of the media stems from their embeddedness in culture and society....

  7. IL-17 is a protection effector against the adherent-invasive Escherichia coli in murine colitis.

    Science.gov (United States)

    Zhang, Hai-Jia; Xu, Bin; Wang, Hu; Xu, Bing; Wang, Guo-Dong; Jiang, Ming-Zuo; Lei, Chao; Ding, Mei-Ling; Yu, Peng-Fei; Nie, Yong-Zhan; Wu, Kai-Chun; Sha, Su-Mei; Li, Meng-Bin

    2018-01-01

    Inflammatory bowel disease (IBD) is caused by aberrant immune responses to the gut microbiota. Among the gut microbiota, adherent-invasive Escherichia Coli (AIEC) is thought to be the pathogen through invading the intestinal epithelial cells and causing inflammation. IL-17 secretion increase, induced by enhanced bacterial adhesion to the intestine epithelium, could on one hand protect the mucosa, but on the other hand, over amount of IL-17 initializes inflammation reactions that in turn damages the mucosa. The relationship between IL-17 and AIEC is still unclear. In this study, we tried to elucidate the function of IL-17 in AIEC-mediated colitis. Wild type (WT) and IL-17 knockout (IL-17 KO) mice were inoculated with AIEC strain E. coli LF82 and treated with dextran sodium sulphate (DSS). Histological examination of the colon was performed. Mucosa damage was assessed and scored. IL-22 and IL-17 in colon tissues were detected by ELISA, qPCR and immunohistochemistry methods. Transient AIEC colonization in IL-17 KO mice resulted in increased intestinal epithelial damage, systemic bacterial burden and mortality compared with WT controls. Moreover, IL-17 is required for the induction of IL-22 in the experimental animal models during AIEC strain E. coli LF82 colonization. These results indicate IL-17 plays a protective role in AIEC strain E. coli LF82 induced colitis by promoting IL-22 secretion. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Vedolizumab: toward a personalized therapy paradigm for people with ulcerative colitis

    Directory of Open Access Journals (Sweden)

    Dart RJ

    2017-03-01

    Full Text Available Robin J Dart,1–3,* Mark A Samaan,1,* Nick Powell,1,4 Peter M Irving1 1Department of Gastroenterology, IBD Centre, St. Thomas’ Hospital, 2Immunosurveillance Laboratory, The Francis Crick Institute, London, 3Division of Immunology, Infection, and Inflammatory Disease (DIIID, King’s College London, 4Department of Experimental Immunobiology, Division of Transplantation and Mucosal Biology, King’s College London, London, UK *These authors contributed equally to this work Abstract: Ulcerative colitis (UC is a chronic relapsing and remitting inflammatory bowel disease, with a characteristic leukocytic infiltration of the mucosa. Immunosuppression including anti-TNF-α therapy is a mainstay of treatment for many; however, systemic immunosuppression is not universally effective and is associated with potential side effects. The gut-tropic integrin α4β7, which is expressed on leukocytes, mediates migration from the circulation to the intestinal mucosa. Vedolizumab is a monoclonal antibody which blocks the egress of leukocytes via α4β7, preventing accumulation in the mucosa, and attenuating inflammation without systemic immunosuppression. Vedolizumab has been evaluated in UC in a phase III trial, demonstrating efficacy as both an induction and a maintenance agent. In this article, we review the clinical trial data and also explore the growing body of “real-world” effectiveness data, investigating response and remission rates of vedolizumab in clinical practice. In addition, we review the increasing volume of data supporting the reassuring safety profile associated with vedolizumab. Keywords: vedolizumab, ulcerative colitis, personalized therapy

  9. Chemistry meets biology in colitis-associated carcinogenesis

    Science.gov (United States)

    Mangerich, Aswin; Dedon, Peter C.; Fox, James G.; Tannenbaum, Steven R.; Wogan, Gerald N.

    2015-01-01

    The intestine comprises an exceptional venue for a dynamic and complex interplay of numerous chemical and biological processes. Here, multiple chemical and biological systems, including the intestinal tissue itself, its associated immune system, the gut microbiota, xenobiotics, and metabolites meet and interact to form a sophisticated and tightly regulated state of tissue homoeostasis. Disturbance of this homeostasis can cause inflammatory bowel disease (IBD) – a chronic disease of multifactorial etiology that is strongly associated with increased risk for cancer development. This review addresses recent developments in research into chemical and biological mechanisms underlying the etiology of inflammation-induced colon cancer. Beginning with a general overview of reactive chemical species generated during colonic inflammation, the mechanistic interplay between chemical and biological mediators of inflammation, the role of genetic toxicology and microbial pathogenesis in disease development are discussed. When possible, we systematically compare evidence from studies utilizing human IBD patients with experimental investigations in mice. The comparison reveals that many strong pathological and mechanistic correlates exist between mouse models of colitis-associated cancer, and the clinically relevant situation in humans. We also summarize several emerging issues in the field, such as the carcinogenic potential of novel inflammation-related DNA adducts and genotoxic microbial factors, the systemic dimension of inflammation-induced genotoxicity, and the complex role of genome maintenance mechanisms during these processes. Taken together, current evidence points to the induction of genetic and epigenetic alterations by chemical and biological inflammatory stimuli ultimately leading to cancer formation. PMID:23926919

  10. Fungal mediated silver nanoparticle synthesis using robust experimental design and its application in cotton fabric

    Science.gov (United States)

    Velhal, Sulbha Girish; Kulkarni, S. D.; Latpate, R. V.

    2016-09-01

    Among the different methods employed for the synthesis of nanoparticles, the biological method is most favorable and quite well established. In microorganisms, use of fungi in the biosynthesis of silver nanoparticles has a greater advantage over other microbial mediators. In this study, intracellular synthesis of silver nanoparticles from Aspergillus terrerus (Thom) MTCC632 was carried out. We observed that synthesis of silver nanoparticles depended on factors such as temperature, amount of biomass and concentration of silver ions in the reaction mixture. Hence, optimization of biosynthesis using these parameters was carried out using statistical tool `robust experimental design'. Size and morphology of synthesized nanoparticles were determined using X-ray diffraction technique, field emission scanning electron microscopy, energy dispersion spectroscopy, and transmission electron microscopy. Nano-embedded cotton fabric was further prepared and studied for its antibacterial properties.

  11. Fucoidan Extracts Ameliorate Acute Colitis.

    Directory of Open Access Journals (Sweden)

    Qi Ying Lean

    Full Text Available Inflammatory bowel diseases (IBD, such as ulcerative colitis and Crohn's disease, are an important cause of morbidity and impact significantly on quality of life. Overall, current treatments do not sustain a long-term clinical remission and are associated with adverse effects, which highlight the need for new treatment options. Fucoidans are complex sulphated, fucose-rich polysaccharides, found in edible brown algae and are described as having multiple bioactivities including potent anti-inflammatory effects. Therefore, the therapeutic potential of two different fucoidan preparations, fucoidan-polyphenol complex (Maritech Synergy and depyrogenated fucoidan (DPF was evaluated in the dextran sulphate sodium (DSS mouse model of acute colitis. Mice were treated once daily over 7 days with fucoidans via oral (Synergy or DPF or intraperitoneal administration (DPF. Signs and severity of colitis were monitored daily before colons and spleens were collected for macroscopic evaluation, cytokine measurements and histology. Orally administered Synergy and DPF, but not intraperitoneal DPF treatment, significantly ameliorated symptoms of colitis based on retention of body weight, as well as reduced diarrhoea and faecal blood loss, compared to the untreated colitis group. Colon and spleen weight in mice treated with oral fucoidan was also significantly lower, indicating reduced inflammation and oedema. Histological examination of untreated colitis mice confirmed a massive loss of crypt architecture and goblet cells, infiltration of immune cells and oedema, while all aspects of this pathology were alleviated by oral fucoidan. Importantly, in this model, the macroscopic changes induced by oral fucoidan correlated significantly with substantially decreased production of at least 15 pro-inflammatory cytokines by the colon tissue. Overall, oral fucoidan preparations significantly reduce the inflammatory pathology associated with DSS-induced colitis and could

  12. Cytokines profiling by multiplex analysis in experimental arthritis: which pathophysiological relevance for articular versus systemic mediators?

    Science.gov (United States)

    Paquet, Joseph; Goebel, Jean-Christophe; Delaunay, Camille; Pinzano, Astrid; Grossin, Laurent; Cournil-Henrionnet, Christel; Gillet, Pierre; Netter, Patrick; Jouzeau, Jean-Yves; Moulin, David

    2012-03-13

    We have taken advantage of the large screening capacity of a multiplex immunoassay to better define the respective contribution of articular versus systemic cytokines in experimental arthritis. We performed a follow up (from 7 hours to 14 days) multiplex analysis of 24 cytokines in synovial fluid and sera of rats developing Antigen-Induced Arthritis (AIA) and confronted their protein level changes with molecular, biochemical, histological and clinical events occurring in the course of the disease. The time-scheduled findings in arthritic joints correlated with time-dependent changes of cytokine amounts in joint effusions but not with their blood levels. From seven hours after sensitization, high levels of chemokines (MCP-1, MIP1α, GRO/KC, RANTES, eotaxin) were found in synovial fluid of arthritic knees whereas perivascular infiltration occurred in the synovium; local release of inflammatory cytokines (IFNγ, IL-1β, IL-6) preceded the spreading of inflammation and resulted in progressive degradation of cartilage and bone. Finally a local overexpression of several cytokines/adipocytokines poorly described in arthritis (IL-13, IL-18, leptin) was observed. Distinct panels of cytokines were found in arthritic fluid during AIA, and the expected effect of mediators correlated well with changes occurring in joint tissues. Moreover, multiplex analysis could be helpful to identify new pathogenic mediators and to elucidate the mechanisms supporting the efficacy of putative targeted therapies.

  13. Opioid pathways activation mediates the activity of nicorandil in experimental models of nociceptive and inflammatory pain.

    Science.gov (United States)

    Dutra, Marcela M G B; Nascimento Júnior, Elias B; Godin, Adriana M; Brito, Ana Mercy S; Melo, Ivo S F; Augusto, Paulo S A; Rodrigues, Felipe F; Araújo, Débora P; de Fátima, Ângelo; Coelho, Márcio M; Machado, Renes R

    2015-12-05

    We have previously demonstrated that nicorandil inhibits the second phase of the nociceptive response induced by formaldehyde. In the present study, we evaluated the effects induced by nicorandil in other models of nociceptive and inflammatory pain in mice and also whether opioid pathways activation mediates its activity. As we have previously demonstrated, per os (p.o.) administration of nicorandil (50, 100 or 150mg/kg; -1h) inhibited the second phase of the nociceptive response induced by intraplantar (i.pl.) injection of formaldehyde. Nicorandil (50, 100 or 150mg/kg; p.o., -1h) also exhibited activity in models of inflammatory pain induced by i.pl. injection of carrageenan (300μg) and nociceptive pain induced by exposure to noxious heat (50°C). Intraperitoneal (i.p.) administration of the opioid antagonist naltrexone (1, 5 or 10mg/kg, -30min) attenuated or abolished the antinociceptive activity of nicorandil (100mg/kg, p.o.) in the three experimental pain models. In conclusion, we demonstrate that nicorandil exhibits activity in different models of nociceptive and inflammatory pain. The demonstration that the antinociceptive effect induced by nicorandil is markedly attenuated by an opioid antagonist provides solid information about an important mechanism mediating the activity of this antianginal drug. Altogether, our data suggest that the clinical pain relief induced by nicorandil in heart ischemic conditions may result from both vasodilation and intrinsic analgesic activity. Copyright © 2015. Published by Elsevier B.V.

  14. An experimental test of insect-mediated colonisation of damaged Pinus radiata trees by sapstain fungi.

    Directory of Open Access Journals (Sweden)

    James K McCarthy

    Full Text Available Vector-pathogen dynamics play a central role in understanding tree health and forest dynamics. There is substantial evidence that bark beetles act as spore vectors for many species of fungi that cause 'sapstain' discolouration of damaged trees and timber. However, the direct quantitative link between vector-mediated spore dispersal and subsequent sapstain colonisation of wood is not fully understood. Here, we used caged versus uncaged experimental logs to test whether the exclusion of bark beetles quantitatively alters the distribution and intensity of sapstain fungal spread within damaged trees. Using generalised linear mixed models, we tested the effect of bark beetle exclusion on sapstain intensity within and among cut logs at two plantation forest sites. Overall, sapstain was found on all logs regardless of caging treatment, indicating that sapstain colonisation can occur (to some degree without arthropod vectors, probably via wind, rain-splash and, potentially, latent endophytic development. This was supported by the dominance of Diplodia pinea in fungal isolations taken from trees felled at the site, as this fungal species is known to disperse independently of bark beetles. However, the intensity of sapstain within and among experimental logs was significantly greater in uncaged than in caged logs, where beetle colonisation was significantly greater. This appeared to be driven by a significant within-log association between the intensity of staining and the intensity of beetle, and other arthropod, tunnelling and feeding activities. Taken together, these results strongly suggest that the dominant mechanism underlying the role of bark beetles in sapstain development in this study system is not vector-mediated spore dispersal, per se, but rather the facilitation of spore entry and hyphal development through tunnelling and feeding activities. We discuss the implications of these findings for forest management and the effective salvage

  15. Increased susceptibility of IDH2-deficient mice to dextran sodium sulfate-induced colitis

    Directory of Open Access Journals (Sweden)

    Hanvit Cha

    2017-10-01

    Full Text Available Inflammatory bowel disease (IBD is a group of chronic, relapsing, immunological, inflammatory disorders of the gastrointestinal tract including ulcerative colitis (UC and Crohn's disease (CD. It has been reported that UC, which is studied using a dextran sodium sulfate (DSS-induced colitis model, is associated with the production of reactive oxygen species (ROS and the apoptosis of intestine epithelial cells (IEC. Mitochondrial NADP+-dependent isocitrate dehydrogenase (IDH2 has been reported as an essential enzyme in the mitochondrial antioxidant system via generation of NADPH. Therefore, we evaluated the role of IDH2 in DSS-induced colitis using IDH2-deficient (IDH2-/- mice. We observed that DSS-induced colitis in IDH2-/- mice was more severe than that in wild-type IDH2+/+ mice. Our results also suggest that IDH2 deficiency exacerbates PUMA-mediated apoptosis, resulting from NF-κB activation regulated by histone deacetylase (HDAC activity. In addition, DSS-induced colitis is ameliorated by an antioxidant N-acetylcysteine (NAC through attenuation of oxidative stress, resulting from deficiency of the IDH2 gene. In conclusion, deficiency of IDH2 leads to increased mitochondrial ROS levels, which inhibits HDAC activity, and the activation of NF-κB via acetylation is enhanced by attenuated HDAC activity, which causes PUMA-mediated apoptosis of IEC in DSS-induced colitis. The present study supported the rationale for targeting IDH2 as an important cancer chemoprevention strategy, particularly in the prevention of colorectal cancer.

  16. Cre-loxP-Mediated Recombination: General Principles and Experimental Considerations.

    Science.gov (United States)

    McLellan, Micheal A; Rosenthal, Nadia A; Pinto, Alexander R

    2017-03-02

    The cre-loxP-mediated recombination system (the "cre-loxP system") is an integral experimental tool for mammalian genetics and cell biology. Use of the system has greatly expanded our ability to precisely interrogate gene function in the mouse, providing both spatial and temporal control of gene expression. This has been largely due to the simplicity of its use and its adaptability to address diverse biological questions. While the use of the cre-loxP system is becoming increasingly widespread, in particular because of growing availability of conditional mouse mutants, many considerations need to be taken into account when utilizing the cre-loxP system. This review provides an overview of the cre-loxP system and its various permutations. It addresses the limitations of cre-loxP technology and related considerations for experimental design, and it discusses alternative strategies for site-specific genetic recombination and integration. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

  17. Experimental taphonomy of Artemia reveals the role of endogenous microbes in mediating decay and fossilization.

    Science.gov (United States)

    Butler, Aodhán D; Cunningham, John A; Budd, Graham E; Donoghue, Philip C J

    2015-06-07

    Exceptionally preserved fossils provide major insights into the evolutionary history of life. Microbial activity is thought to play a pivotal role in both the decay of organisms and the preservation of soft tissue in the fossil record, though this has been the subject of very little experimental investigation. To remedy this, we undertook an experimental study of the decay of the brine shrimp Artemia, examining the roles of autolysis, microbial activity, oxygen diffusion and reducing conditions. Our findings indicate that endogenous gut bacteria are the main factor controlling decay. Following gut wall rupture, but prior to cuticle failure, gut-derived microbes spread into the body cavity, consuming tissues and forming biofilms capable of mediating authigenic mineralization, that pseudomorph tissues and structures such as limbs and the haemocoel. These observations explain patterns observed in exceptionally preserved fossil arthropods. For example, guts are preserved relatively frequently, while preservation of other internal anatomy is rare. They also suggest that gut-derived microbes play a key role in the preservation of internal anatomy and that differential preservation between exceptional deposits might be because of factors that control autolysis and microbial activity. The findings also suggest that the evolution of a through gut and its bacterial microflora increased the potential for exceptional fossil preservation in bilaterians, providing one explanation for the extreme rarity of internal preservation in those animals that lack a through gut.

  18. Microscopic colitis: Is it a spectrum of inflammatory bowel disease?

    OpenAIRE

    Jegadeesan, Ramprasad; Liu, Xiuli; Pagadala, Mangesh R; Gutierrez, Norma; Butt, Mujtaba; Navaneethan, Udayakumar

    2013-01-01

    Lymphocytic and collagenous colitis are forms of microscopic colitis which typically presents in elderly patients as chronic watery diarrhea. The association between microscopic colitis and inflammatory bowel disease is weak and unclear. Lymphocytic colitis progressing to ulcerative colitis has been previously reported; however there is limited data on ulcerative colitis evolving into microscopic (lymphocytic or collagenous) colitis. We report a series of six patients with documented ulcerati...

  19. A novel pyrazole-containing indolizine derivative suppresses NF-κB activation and protects against TNBS-induced colitis via a PPAR-γ-dependent pathway.

    Science.gov (United States)

    Fu, Yong; Ma, Junting; Shi, Xiafei; Song, Xiang-Yun; Yang, Yaping; Xiao, Shuke; Li, Jiahuang; Gu, Wei-Jin; Huang, Zhen; Zhang, Junfeng; Chen, Jiangning

    2017-07-01

    The nuclear factor-κB (NF-κB)-mediated activation of macrophages plays a key role in mucosal immune responses in Crohn's disease (CD). Moreover, increasing evidence shows that the activation of peroxisome proliferator-activated receptor-γ (PPAR-γ) exerts satisfactory anti-inflammatory effects in experimental colitis models, mostly by suppressing NF-κB-mediated macrophage activation. Therefore, exploring therapeutic strategies to activate PPAR-γ and inhibit the NF-κB pathway in colonic macrophages holds great promise for the treatment of CD. In this study, five novel pyrazole-containing indolizine derivatives (B1, B2, B3, B4 and B5) were successfully synthesized and characterized, and their anti-inflammatory activities for CD treatment were also investigated. Among the five compounds, compound B4 effectively decreased the NF-κB-mediated production of the pro-inflammatory cytokine TNF-α in LPS-stimulated peritoneal macrophages. Moreover, compound B4 significantly ameliorated 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced mouse colitis symptoms, including body weight loss, colonic pathological damage and inflammatory cell infiltration. The results of western blotting and luciferase reporter assays indicated that compound B4 activated PPAR-γ and subsequently suppressed NF-κB activation. Conversely, the addition of the PPAR-γ antagonist GW9662 abrogated the anti-inflammatory effects of compound B4 both in vitro and in vivo. In summary, compound B4 activated the PPAR-γ pathway to inhibit downstream NF-κB signaling, which alleviated experimental colitis. Thus, this compound may serve as a potential therapeutic agent for patients with CD. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Effect of Niacin on Inflammation and Angiogenesis in a Murine Model of Ulcerative Colitis

    OpenAIRE

    Salem, Hesham Aly; Wadie, Walaa

    2017-01-01

    Butyrate and niacin are produced by gut microbiota, however butyrate has received most attention for its effects on colonic health. The present study aimed at exploring the effect of niacin on experimental colitis as well as throwing some light on the ability of niacin to modulate angiogenesis which plays a crucial role of in the pathogenesis of inflammatory bowel disease. Rats were given niacin for 2 weeks. On day 8, colitis was induced by intrarectal administration of iodoacetamide. Rats we...

  1. Confocal laser endomicroscopy in ulcerative colitis

    DEFF Research Database (Denmark)

    Karstensen, John Gásdal; Săftoiu, Adrian; Brynskov, Jørn

    2016-01-01

    was to correlate colonic confocal laser endomicroscopy (CLE) in ulcerative colitis with histopathology and macroscopic appearance before and after intensification of medical treatment. METHODS: Twenty-two patients with ulcerative colitis in clinical relapse and 7 control subjects referred for colonoscopy were...... colitis compared with inactive ulcerative colitis...... is an emerging endoscopic technique that reproducibly identifies mucosal changes in ulcerative colitis. With the exception of crypt changes, endomicroscopic features appear to improve slowly with time after medical treatment. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT01684514.)....

  2. β-Caryophyllene attenuates dextran sulfate sodium-induced colitis in mice via modulation of gene expression associated mainly with colon inflammation

    Directory of Open Access Journals (Sweden)

    Jae Young Cho

    2015-01-01

    Full Text Available We examined the modulatory activity of β-caryophyllene (CA and gene expression in colitic colon tissues in a dextran sulfate sodium (DSS-induced colitis model. Experimental colitis was induced by exposing male BALB/c mice to 5% DSS in drinking water for 7 days. CA (30 or 300 mg/kg was administered orally once a day together with DSS. CA administration attenuated the increases in the disease activity index, colon weight/length ratio, inflammation score, and myeloperoxidase activity in DSS-treated mice. Microarray analysis showed that CA administration regulated the expression in colon tissue of inflammation-related genes including those for cytokines and chemokines (Ccl2, Ccl7, Ccl11, Ifitm3, IL-1β, IL-28, Tnfrsf1b, Tnfrsf12a; acute-phase proteins (S100a8, Saa3, Hp; adhesion molecules (Cd14, Cd55, Cd68, Mmp3, Mmp10, Sema6b, Sema7a, Anax13; and signal regulatory proteins induced by DSS. CA significantly suppressed NF-κB activity, which mediates the expression of a different set of genes. These results suggest that CA attenuates DSS-induced colitis, possibly by modulating the expression of genes associated mainly with colon inflammation through inhibition of DSS-induced NF-κB activity.

  3. [Ipilimumab-induced colitis: A new challenge for gastroenterologists].

    Science.gov (United States)

    Mesonero, Francisco; López-Sanromán, Antonio; Madariaga, Ainhoa; Soria, Ainara

    2016-03-01

    Many drugs can produce enterocolitis and they should always be included in the differential diagnosis of this clinical picture. Entities such as antibiotic-associated colitis and neutropenic colitis have been known for some time and recently a new type of drug-induced colitis has emerged due to monoclonal antibodies. Ipimumab is a humanized monoclonal antibody against the CTLA4 molecule that is involved in the maturation and regulation of T lymphocyte activation. This drug causes immune activation and has an immune-mediated antitumor effect with excellent results in tumours such as melanoma. However, several immune-related adverse effects may occur in different organs. The most frequently involved site is the gastrointestinal tract, with adverse effects ranging from mild diarrhoea to colitis with systemic involvement, intestinal perforation, and even death. Although no similarities have been found in the pathogenesis with inflammatory bowel disease, treatments have been used in correlation with its autoimmunological profile: anti-TNF alpha corticosteroids have shown clinical efficacy in moderate to severe disease. However the use of anti-TNF treatment has not been defined and the safety profile is unknown. The inclusion of these new therapies in the treatment of several tumours requires familiarity with these entities and their management should be approached as a new challenge for the gastroenterologist. For that reason, we conducted a review of ipilimumab-induced colitis, evaluating essential features of its symptoms, diagnosis and treatment. Copyright © 2015 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

  4. The application of molecular topology for ulcerative colitis drug discovery.

    Science.gov (United States)

    Bellera, Carolina L; Di Ianni, Mauricio E; Talevi, Alan

    2018-01-01

    Although the therapeutic arsenal against ulcerative colitis has greatly expanded (including the revolutionary advent of biologics), there remain patients who are refractory to current medications while the safety of the available therapeutics could also be improved. Molecular topology provides a theoretic framework for the discovery of new therapeutic agents in a very efficient manner, and its applications in the field of ulcerative colitis have slowly begun to flourish. Areas covered: After discussing the basics of molecular topology, the authors review QSAR models focusing on validated targets for the treatment of ulcerative colitis, entirely or partially based on topological descriptors. Expert opinion: The application of molecular topology to ulcerative colitis drug discovery is still very limited, and many of the existing reports seem to be strictly theoretic, with no experimental validation or practical applications. Interestingly, mechanism-independent models based on phenotypic responses have recently been reported. Such models are in agreement with the recent interest raised by network pharmacology as a potential solution for complex disorders. These and other similar studies applying molecular topology suggest that some therapeutic categories may present a 'topological pattern' that goes beyond a specific mechanism of action.

  5. Association Between Proton Pump Inhibitors and Microscopic Colitis.

    Science.gov (United States)

    Law, Ernest H; Badowski, Melissa; Hung, Yu-Ting; Weems, Kimberly; Sanchez, Angelica; Lee, Todd A

    2017-03-01

    Microscopic colitis (MC) is a chronic inflammatory disease of the colon that is characterized by chronic, watery, nonbloody diarrhea. Concern regarding a potential association between proton-pump inhibitors (PPIs) and MC has recently emerged. We sought to systematically review and summarize the evidence for the potential association between PPIs and MC. We systematically searched EMBASE, MEDLINE, Cochrane Database of Systematic Reviews, International Pharmaceutical Abstracts, and Google Scholar using the terms proton-pump inhibitors (omeprazole, lansoprazole, dexlansoprazole, rabeprazole, pantoprazole, or esomeprazole), microscopic colitis, collagenous colitis, and lymphocytic colitis. Full-text, English-language reports of case reports/series, observational studies, experimental studies, and systematic reviews/meta-analyses published between January 2000 to August 2016 were included. Bibliographies from pertinent publications were reviewed for additional references. Outcome was defined as the development of biopsy-confirmed MC. A total of 19 publications were identified: 5 case control studies and 14 case reports/series (encompassing a total of 32 cases). All studies were limited by small sample sizes. Risk of MC by dose or specific PPI agent was not investigated in any of the studies. A review of the current body of evidence reveals a possible association between PPIs and MC. There is a need for large observational studies of high quality to examine the differential effect of specific PPIs and whether the magnitude of association is dose dependent. Given their widespread use, clinicians should routinely question whether patients are receiving unnecessary treatment with PPIs and discontinue therapy where appropriate.

  6. Econometric Mediation Analyses: Identifying the Sources of Treatment Effects from Experimentally Estimated Production Technologies with Unmeasured and Mismeasured Inputs.

    Science.gov (United States)

    Heckman, James; Pinto, Rodrigo

    2015-01-01

    This paper presents an econometric mediation analysis. It considers identification of production functions and the sources of output effects (treatment effects) from experimental interventions when some inputs are mismeasured and others are entirely omitted. JEL Code: D24, C21, C43, C38.

  7. Consumers mediate the effects of experimental ocean acidification and warming on primary producers.

    Science.gov (United States)

    Alsterberg, Christian; Eklöf, Johan S; Gamfeldt, Lars; Havenhand, Jonathan N; Sundbäck, Kristina

    2013-05-21

    It is well known that ocean acidification can have profound impacts on marine organisms. However, we know little about the direct and indirect effects of ocean acidification and also how these effects interact with other features of environmental change such as warming and declining consumer pressure. In this study, we tested whether the presence of consumers (invertebrate mesograzers) influenced the interactive effects of ocean acidification and warming on benthic microalgae in a seagrass community mesocosm experiment. Net effects of acidification and warming on benthic microalgal biomass and production, as assessed by analysis of variance, were relatively weak regardless of grazer presence. However, partitioning these net effects into direct and indirect effects using structural equation modeling revealed several strong relationships. In the absence of grazers, benthic microalgae were negatively and indirectly affected by sediment-associated microalgal grazers and macroalgal shading, but directly and positively affected by acidification and warming. Combining indirect and direct effects yielded no or weak net effects. In the presence of grazers, almost all direct and indirect climate effects were nonsignificant. Our analyses highlight that (i) indirect effects of climate change may be at least as strong as direct effects, (ii) grazers are crucial in mediating these effects, and (iii) effects of ocean acidification may be apparent only through indirect effects and in combination with other variables (e.g., warming). These findings highlight the importance of experimental designs and statistical analyses that allow us to separate and quantify the direct and indirect effects of multiple climate variables on natural communities.

  8. Lipid A's structure mediates Neisseria gonorrhoeae fitness during experimental infection of mice and men.

    Science.gov (United States)

    Hobbs, Marcia M; Anderson, James E; Balthazar, Jacqueline T; Kandler, Justin L; Carlson, Russell W; Ganguly, Jhuma; Begum, Afrin A; Duncan, Joseph A; Lin, Jessica T; Sparling, P Frederick; Jerse, Ann E; Shafer, William M

    2013-11-19

    Phosphoethanolamine (PEA) on Neisseria gonorrhoeae lipid A influences gonococcal inflammatory signaling and susceptibility to innate host defenses in in vitro models. Here, we evaluated the role of PEA-decorated gonococcal lipid A in competitive infections in female mice and in male volunteers. We inoculated mice and men with mixtures of wild-type N. gonorrhoeae and an isogenic mutant that lacks the PEA transferase, LptA. LptA production conferred a marked survival advantage for wild-type gonococci in the murine female genital tract and in the human male urethra. Our studies translate results from test tube to animal model and into the human host and demonstrate the utility of the mouse model for studies of virulence factors of the human-specific pathogen N. gonorrhoeae that interact with non-host-restricted elements of innate immunity. These results validate the use of gonococcal LptA as a potential target for development of novel immunoprophylactic strategies or antimicrobial treatments. Gonorrhea is one of the most common bacterial sexually transmitted infections, and increasing antibiotic resistance threatens the use of currently available antimicrobial therapies. In this work, encompassing in vitro studies and in vivo studies of animal and human models of experimental genital tract infection, we document the importance of lipid A's structure, mediated by a single bacterial enzyme, LptA, in enhancing the fitness of Neisseria gonorrhoeae. The results of these studies suggest that novel agents targeting LptA may offer urgently needed prevention or treatment strategies for gonorrhea.

  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. 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...

  11. Olanzapine-induced ischemic colitis

    Directory of Open Access Journals (Sweden)

    Esteban Sáez-González

    Full Text Available Background: Ischemic colitis (IC is an uncommon adverse event associated with antipsychotic agents, more commonly found with phenothiazine drugs and atypical neuroleptics such as clozapine. The risk of developing ischemic colitis increases when anticholinergic drugs are associated. Case report: We report the case of a 38-year-old woman with a history of schizoaffective disorder who had been on chronic quetiapine for 3 years, and presented to the ER because of diarrhea for 5 days. Four months previously, olanzapine had been added to her psychiatric drug regimen. Physical examination revealed abdominal distension with abdominal tympanic sounds and tenderness. Emergency laboratory tests were notable for increased acute phase reagents. Tomography revealed a concentric thickening of the colonic wall in the transverse, descending and sigmoid segments, with no signs of intestinal perforation. Colonoscopy demonstrated severe mucosal involvement from the sigmoid to the hepatic flexure, with ulcerations and fibrinoid exudate. Biopsies confirmed the diagnosis of ischemic colitis. The only relevant finding in her history was the newly added drug to her baseline regimen. An adverse effect was suspected because of its anticholinergic action at the intestinal level, and the drug was withdrawn. After 6 months of follow-up clinical, laboratory and endoscopic recovery was achieved. Discussion: Antipsychotic medication should be considered as a potential cause of ischemic colitis, particularly atypical antipsychotics such as clozapine and olanzapine; despite being uncommon, this adverse event may result in high morbidity and mortality.

  12. [Ulcerative colitis and cytomegalovirus infection].

    Science.gov (United States)

    Tárraga Rodríguez, I; Ferreras Fernández, P; Vicente Gutiérrez, M; de Arriba, J J; García Mouriño, M L

    2003-02-01

    Colitis ulcerous and citomegalovirus infection association have been reported in medical literature in sometimes, althougth this prevalence have lately increased. We report a case record of this association and do a review of this subject. It is not clear what factors are involved in this association, being necessary hore studies to know them.

  13. Microscopic colitis: A literature review.

    Science.gov (United States)

    Clara, Ana Paula Hamer Sousa; Magnago, Flávia Drago; Ferreira, Juliana Neves; Grillo, Thais Gagno

    2016-12-01

    Microscopic colitis (MC) refers to chronic inflammation of the colon which is characterized by histologic changes at the level of a radiologically and endoscopically normal mucosa. It is a common cause of chronic non-bloody diarrhea that occurs primarily in older individuals; however, there are few studies in the literature with strong scientific evidence compared to other inflammatory bowel diseases (IBD), which limits the knowledge of physicians and pathologists. This article aims to review the information on MC, describing diagnostic methods and drugs available for treatment. We conducted a search of the Pubmed database and CAPES Portal using the keywords "microscopic colitis", "collagenous colitis", "lymphocytic colitis", and "review" for selection of articles published between 1996 and 2015 related to the topic. Based on the studies discussed in this review, we conclude that MC is a relatively new gastrointestinal disorder, most studies are incipient particularly with respect to pathophysiology and immunology, and budesonide is the best documented short-term treatment. However, further studies are needed to elucidate the best strategy for treatment in the long term.

  14. Colonic miRNA expression/secretion, regulated by intestinal epithelial PepT1, plays an important role in cell-to-cell communication during colitis.

    Directory of Open Access Journals (Sweden)

    Saravanan Ayyadurai

    Full Text Available PepT1 is a member of the proton-oligopeptide cotransporter family SLC15, which mediates the transport of di/tripeptides from intestinal lumen into epithelial cells. MicroRNAs (miRNAs, a small noncoding RNAs (21-23 nucleotides, post-transcriptionally regulate gene expression by binding to the 3'-untranslated regions (UTRs of their target mRNAs. Although the role of most miRNAs remains elusive, they have been implicated in vital cellular functions such as intestinal epithelial cells differentiation, proliferation, and apoptosis. In the present study, we investigated the effect of intestinal epithelial PepT1 expression on microRNA (miRNA expression/secretion in the colons of control mice and in mice with experimentally induced colonic inflammation (colitis. The colonic miRNA expression was deregulated in both colitis and control mice but the deregulation of miRNA expression/secretion was specific to colonic tissue and did not affect other tissues such as spleen and liver. Intestinal epithelial PepT1-dependent deregulation of colonic miRNA expression not only affects epithelial cells but also other cell types, such as intestinal macrophages. Importantly, we found the miRNA 23b which was known to be involved in inflammatory bowel disease was secreted and transported between cells to impose a gene-silencing effect on recipient intestinal macrophages. Based on our data, we may conclude that the expression of a specific protein, PepT1, in the intestine affects local miRNA expression/secretion in the colon on a tissue specific manner and may play an important role during the induction and progression of colitis. Colonic miRNA expression/secretion, regulated by intestinal epithelial PepT1, could play a crucial role in cell-to-cell communication during colitis.

  15. Apple polyphenols extract (APE) improves colon damage in a rat model of colitis.

    Science.gov (United States)

    D'Argenio, Giuseppe; Mazzone, Giovanna; Tuccillo, Concetta; Ribecco, Maria T; Graziani, Giulia; Gravina, Antonietta G; Caserta, Sergio; Guido, Stefano; Fogliano, Vincenzo; Caporaso, Nicola; Romano, Marco

    2012-07-01

    Searching for alternative therapies that are effective, safe and less expensive of those currently used for ulcerative colitis, we investigated the efficacy of a polyphenol extract from apple in rat colitis. Rats with trinitrobenzensulphonic acid-induced colitis were treated daily with rectal administration of apple polyphenols 10(-4) M for 14 days. COX-2, TNF-α, tissue transglutaminase and calpain in colon mucosa samples were assessed by reverse transcription-polymerase chain reaction and western blot analyses. To ascertain the role of tissue transglutaminase in mucosal healing, wounded rat fibroblasts were incubated with cystamine (a tissue transglutaminase activity inhibitor). Colitis was associated with increased COX-2, TNF-α, calpain, and tissue transglutaminase mRNA. The protein expression of COX-2, TNF-α and calpain was increased whilst tissue transglutaminase was decreased. Apple extract treatment reduced the severity of colitis (pApple polyphenols reduced the degradation of tissue transglutaminase protein occurring through calpain action. Apple polyphenols-treated wounded fibroblast recovered within 24h showing intense immunoreactivity for tissue transglutaminase. The efficacy of apple extract is mediated by its effects on COX-2 and TNF-α. The unbalance between calpain and tissue transglutaminase may play a role in colonic damage and future therapeutic interventions in ulcerative colitis can target this mechanisms. Copyright © 2012 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  16. Contribution of epithelial innate immunity to systemic protection afforded by prolyl hydroxylase inhibition in murine colitis

    Science.gov (United States)

    Keely, Simon; Campbell, Eric L.; Baird, Alan W.; Hansbro, Philip M.; Shalwitz, Robert A.; Kotsakis, Anna; McNamee, Eoin N.; Eltzschig, Holger K.; Kominsky, Douglas J.; Colgan, Sean P.

    2013-01-01

    Pharmacological stabilization of hypoxia-inducible factor (HIF) through prolyl hydroxylase (PHD) inhibition limits mucosal damage associated with models of murine colitis. However, little is known about how PHD inhibitors (PHDi) influence systemic immune function during mucosal inflammation or the relative importance of immunological changes to mucosal protection. We hypothesized that PHDi enhances systemic innate immune responses to colitis-associated bacteremia. Mice with colitis induced by TNBS were treated with AKB-4924, a new HIF-1 isoform-predominant PHDi and clinical, immunological and biochemical endpoints were assessed. Administration of AKB-4924 led to significantly reduced weight loss and disease activity compared to vehicle controls. Treated groups were pyrexic, but did not become subsequently hypothermic. PHDi treatment augmented epithelial barrier function and led to an approximately 50-fold reduction in serum endotoxin during colitis. AKB-4924 also decreased cytokines involved in pyrogenesis and hypothermia, significantly reducing serum levels of IL-1β, IL-6 and TNF-α, while increasing IL-10. Treatment offered no protection against colitis in epithelial-specific HIF-1α deficient mice, strongly implicating epithelial HIF-1α as the tissue target for AKB-4924-mediated protection. Taken together, these results indicate that inhibition of prolyl hydroxylase with AKB-4924 enhances innate immunity and identifies the epithelium is a central site of inflammatory protection afforded by PHDi in murine colitis. PMID:23695513

  17. Hemidesmosome integrity protects the colon against colitis and colorectal cancer

    OpenAIRE

    Hamade, Hussein; Alpy, Fabien; Normand, Sylvain; Bruyere, Emilie; Lefebvre, Olivier; Mechine-Neuville, Agnes; Siebert, Stefanie; Pfister, Véronique; Lepage, Patricia; Laquerriere, Patrice; Dembele, Doulaye; Delanoye-Crespin, Anne; Rodius, Sophie; Robine, Sylvie; Kedinger, Michele

    2017-01-01

    Objective Epidemiological and clinical data indicate that patients suffering from IBD with long-standing colitis display a higher risk to develop colorectal high-grade dysplasia. Whereas carcinoma invasion and metastasis rely on basement membrane (BM) disruption, experimental evidence is lacking regarding the potential contribution of epithelial cell/BM anchorage on inflammation onset and subsequent neoplastic transformation of inflammatory lesions. Herein, we analyse the role of the alpha 6 ...

  18. 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...

  19. Tubercular colitis masquerading as ischemic colitis: An unusual presentation

    Directory of Open Access Journals (Sweden)

    Vishal Sharma

    2017-01-01

    Full Text Available Tuberculosis is a common clinical problem which can involve virtually any organ and mimic a multitude of clinical conditions. Colonic tuberculosis is a type of intestinal tuberculosis which involves the colon and mimics inflammatory bowel disease. Occasionally, it is also confused with colonic malignancy. We report the case of a young female who presented with abdominal pain, bleeding per rectum. Abdominal X-ray showed evidence of thumb-printing. A possibility of ischemic colitis was entertained. However, further investigation unraveled the presence of tubercular colitis. The patient improved with anti-tubercular therapy. Colonic tuberculosis can mimic a number of clinical entities and should be considered in differential diagnosis of colonic lesions in endemic areas.

  20. Synchronous Occurrence of Collagenous and Pseudomembranous Colitis

    Directory of Open Access Journals (Sweden)

    Z Vesoulis

    2000-01-01

    Full Text Available Synchronous collagenous and pseudomembranous colitis has not been previously reported. A 73-year-old woman presented with chronic watery diarrhea and abdominal cramping of six weeks’ duration. Biopsies of the colon revealed findings of collagenous colitis involving the endoscopically normal right colon, and superimposed collagenous and pseudomembranous colitis involving the rectosigmoid colon. Endoscopically, the left colon revealed discrete ulcerative plaques, and Clostridium difficile toxin A assay was positive. The patient partially responded to a three-week regimen of metronidazole, and symptoms resolved completely with subsequent steroid therapy. At follow-up endoscopy four months later, colon biopsies demonstrated persistence of subepithelial collagen but no pseudomembranes. The patient remained asymptomatic during this interval. Collagenous colitis has been reported in association with other inflammatory bowel diseases, including lymphocytic colitis, sprue and idiopathic inflammatory bowel disease. This unique association of collagenous colitis with an endotoxigenic inflammatory bowel disease is presented with a review of related disease features.

  1. Lymphocytic colitis: a distinct clinical entity? A clinicopathological confrontation of lymphocytic and collagenous colitis

    NARCIS (Netherlands)

    Baert, F.; Wouters, K.; D'Haens, G.; Hoang, P.; Naegels, S.; D'Heygere, F.; Holvoet, J.; Louis, E.; Devos, M.; Geboes, K.

    1999-01-01

    It is not known whether lymphocytic colitis and collagenous colitis represent different clinical entities or constitute part of a spectrum of disease. Detailed clinical features and histological findings were compared in a large series of patients with confirmed lymphocytic and collagenous colitis.

  2. Microscopic Colitis: A Review of Collagenous and Lymphocytic Colitis

    Science.gov (United States)

    Boland, Karen

    2017-01-01

    Microscopic colitis (MC) is a chronic inflammatory bowel disease characterized by chronic watery diarrhea and diagnosed with the histologic hallmarks of disease despite a macroscopically normal large bowel. Although 2 distinct disease phenotypes exist, their clinical presentations and epidemiologic characteristics have overlapping features. This article summarizes evidence regarding the pathogenesis of MC, mechanisms of diarrhea in this cohort, and associations with medications. In addition, currently recommended and novel therapeutic approaches to achieving remission in this patient population are reviewed. PMID:29230146

  3. Microscopic Colitis: An Approach to Treatment

    Directory of Open Access Journals (Sweden)

    Nilesh Chande

    2008-01-01

    Full Text Available Microscopic colitis – including collagenous colitis and lymphocytic colitis – causes chronic watery diarrhea, usually in middle-aged or elderly patients. There is an association with celiac disease and certain medications. Medical treatment includes various antidiarrheal agents, mesalamine, corticosteroids and immunosuppressant drugs. Rarely, patients require surgery for refractory disease. An evidence-based and practical approach to treatment should optimize the treatment response while minimizing potential adverse events.

  4. Assessing Team Learning in Technology-Mediated Collaboration: An Experimental Study

    Science.gov (United States)

    Andres, Hayward P.; Akan, Obasi H.

    2010-01-01

    This study examined the effects of collaboration mode (collocated versus non-collocated videoconferencing-mediated) on team learning and team interaction quality in a team-based problem solving context. Situated learning theory and the theory of affordances are used to provide a framework that describes how technology-mediated collaboration…

  5. 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.

  6. 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 of at...... of atypical inflammatory bowel disease (IBD) patients. Our aim was to identify the prevalence of atypical disease patterns in new-onset pediatric UC using the Paris classification.......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...

  7. Campylobacter colitis: Rare cause of toxic megacolon

    Directory of Open Access Journals (Sweden)

    Michael Kwok, MBBS

    2016-01-01

    Conclusion: Toxic megacolon should be considered in a patient with Campylobacter colitis who becomes critically unwell. Despite treatment, toxic megacolon is associated with a significant risk of mortality.

  8. Microscopic colitis: a therapeutic challenge.

    Science.gov (United States)

    Guslandi, Mario

    2013-06-21

    The treatment of microscopic colitis is mainly based on the use of budesonide, the only drug found effective in controlled clinical trials. After an initial course at a dose of 9 mg daily, however, most patients relapse when the drug is discontinued, hence a maintenance therapy at doses of 6 mg daily or lower is necessary. In order to avoid steroid dependence and drug toxicity different pharmacological agents should be considered as an alternative to indefinite long-term budesonide treatment. Evidence-based guidelines are currently lacking due to the lack of conclusive data concerning the use of either immunosuppressive or anti-tumor necrosis factor agents. For the time being in clinical practice the skilled physician should therefore tailor long term management of microscopic colitis on the single patient.

  9. Topical Rosiglitazone Treatment Improves Ulcerative Colitis by Restoring Peroxisome Proliferator-Activated Receptor-gamma Activity

    DEFF Research Database (Denmark)

    Pedersen, G.; Brynskov, Jørn

    2010-01-01

    and functional activity in human colonic epithelium and explored the potential of topical treatment with rosiglitazone (a PPAR gamma ligand) in patients with ulcerative colitis. METHODS: Spontaneous and rosiglitazone-mediated PPAR gamma and adipophillin expression (a gene transcriptionally activated by PPAR...

  10. Therapeutic effect of imiquimod on dextran sulfate sodium-induced ulcerative colitis in mice.

    Directory of Open Access Journals (Sweden)

    Lu Chen

    Full Text Available Imiquimod is a Toll-like receptor-7 agonist that regulates immunity and can be used as an immune adjuvant. Ulcerative colitis has a close correlation with immune disorder.To investigate the therapeutic effect of imiquimod on dextran sulfate sodium (DSS-induced colitis and explore the underlying mechanisms.C57BL/6J C57 mice received 3% DSS for 7 days to induce ulcerative colitis. Groups of mice were intraperitoneally injected with dexamethasone (DXM, 1.5 mg/kg or imiquimod (IMQ, 30 mg/kg at the same time daily. During the experimental period, clinical signs, body weight, stool consistency and visible fecal blood were monitored and recorded daily; colitis was evaluated by disease activity index (DAI score and by histological score. At the conclusion of the experiment, the level of colonic myeloperoxidase (MPO activity and the serum levels of the cytokines tumor necrosis factor-α (TNF-α, interleukin 6 (IL-6 and interleukin 10 (IL-10 were measured.Administration of 3% DSS for 7 days successfully induced acute colitis associated with diarrhea, bloody mucopurulent stool, body weight decreases, and other changes. Colitis severity was significantly ameliorated in the IMQ treatment groups, as determined by hematoxylin-eosin (HE staining and histopathological scores. Moreover, IMQ significantly reduced the activity of MPO in colonic tissue and the serum levels of inflammatory cytokines, increased colon length and spleen weight, and effectively inhibited microscopic damage to the colon tissue.IMQ had beneficial effects on DSS-induced ulcerative colitis, supporting its further development and clinical application in ulcerative colitis.

  11. Advances in knowledge on microscopic colitis: From bench to bedside.

    Science.gov (United States)

    Guagnozzi, D; Lucendo, A J

    2015-02-01

    Microscopic colitis (MC) is a general term that describes a family of chronic inflammatory bowel diseases, including lymphocytic colitis (LC) and collagenous colitis (CC). The two forms are characterized by chronic watery diarrhea with normal or near normal endoscopic colonic appearance and specific histopathological abnormalities.Data from recent epidemiological studies reported the diagnosis of MC from several different regions in the world, providing that it can be a worldwide condition. The etiopathogenesis of MC still remains unknown but it is generally accepted that MC is a multifactorial disease, probably secondary to an abnormal immune reaction in predisposed individuals, triggered by different luminal factors (infections, drugs, autoimmunity and/or bile acids). Furthermore, some studies show that the epithelial barrier function in the colonic mucosa of MC patients is also impaired. Several mucosal factors of intestinal inflammation have been studied in MC, postulating that an aberrant T-lymphocyte response may lead to a chronic gut inflammatory condition, with the infiltration of colonic mucosa by different proportion of subset of T-lymphocytes. Little is known about the specific inflammatory mediators in MC pathogenesis, but a predominant Th1 type cytokine profile has been demonstrated. Currently, a number of medical treatments have been studied in MC patients, following mainly an empirical treatment approach. Further studies are needed in order to obtain prospective and more evidence-based data. In the future, it will be possible to develop causal treatment approaches after better understanding the molecular mechanisms behind the origin of the disease.

  12. Advances in knowledge on microscopic colitis: from bench to bedside

    Directory of Open Access Journals (Sweden)

    Danila Guagnozzi

    Full Text Available Microscopic colitis (MC is a general term that describes a family of chronic inflammatory bowel diseases, including lymphocytic colitis (LC and collagenous colitis (CC. The two forms are characterized by chronic watery diarrhea with normal or near normal endoscopic colonic appearance and specific histopathological abnormalities. Data from recent epidemiological studies reported the diagnosis of MC from several different regions in the world, providing that it can be a worldwide condition. The etiopathogenesis of MC still remains unknown but it is generally accepted that MC is a multifactorial disease, probably secondary to an abnormal immune reaction in predisposed individuals, triggered by different luminal factors (infections, drugs, autoimmunity and/or bile acids. Furthermore, some studies show that the epithelial barrier function in the colonic mucosa of MC patients is also impaired. Several mucosal factors of intestinal inflammation have been studied in MC, postulating that an aberrant T-lymphocyte response may lead to a chronic gut inflammatory condition, with the infiltration of colonic mucosa by different proportion of subset of T-lymphocytes. Little is known about the specific inflammatory mediators in MC pathogenesis, but a predominant Th1 type cytokine profile has been demonstrated. Currently, a number of medical treatments have been studied in MC patients, following mainly an empirical treatment approach. Further studies are needed in order to obtain prospective and more evidence-based data. In the future, it will be possible to develop causal treatment approaches after better understanding the molecular mechanisms behind the origin of the disease.

  13. Anti-inflammatory effect of obestatin and ghrelin in dextran sulfate sodium-induced colitis in rats.

    Science.gov (United States)

    Pamukcu, Ozge; Kumral, Zarife Nigar Ozdemir; Ercan, Feriha; Yegen, Berrak C; Ertem, Deniz

    2013-08-01

    Obestatin and ghrelin are hormones derived from the same gene but have opposing effects. Ghrelin has anti-inflammatory activities; however, the role of obestatin in the inflammatory processes has not been clearly demonstrated yet. The aim of the study was to analyse and compare the anti-inflammatory effect of exogenous ghrelin and obestatin in a rat model of colitis. Acute and chronic colitis was induced in 96 rats by adding 3% dextran sulfate sodium to the drinking water for 5 and 10 days, respectively. Intraperitoneal pretreatment with ghrelin or obestatin was started before the induction of colitis, and continued for 5 and 10 days. Clinical signs of the disease and histopathological changes were evaluated. By-products of neutrophil activation, lipid peroxidation, and inflammatory and anti-inflammatory cytokines were measured in colonic tissues. Obestatin and ghrelin significantly ameliorated clinical and histopathological severity of chronic colitis, whereas they were less effective in the acute form. Therapeutic effect of ghrelin and obestatin in acute colitis was associated with reduced lipid peroxidation and TH1-induced inflammatory response, whereas obestatin in chronic colitis was protective via the suppression of polymorphonuclear leukocyte infiltration and enhancement of glutathione synthesis. Moreover, therapeutic effects of ghrelin and obestatin in chronic colitis appear to be associated with inhibition of inflammatory and activation of anti-inflammatory cytokines. This study demonstrated the novel anti-inflammatory effect of obestatin and ghrelin in an experimental model of colitis. Although both obestatin and ghrelin exerted anti-inflammatory effects in chronic colitis, they were less effective in acute colitis.

  14. Low bone mass in microscopic colitis.

    Science.gov (United States)

    Lorinczy, Katalin; Lakatos, Gábor; Müllner, Katalin; Hritz, István; Lakatos, Péter László; Tulassay, Zsolt; Miheller, Pál

    2011-05-19

    Microscopic colitis presents with similar symptoms to classic inflammatory bowel diseases. Osteoporosis is a common complication of Crohn's disease but there are no data concerning bone metabolism in microscopic colitis. The aim of the present study was to evaluate bone density and metabolism in patients with microscopic colitis. Fourteen patients microscopic colitis were included in the study, and 28 healthy persons and 28 age and gender matched Crohn's disease patients were enrolled as controls. Bone mineral density was measured using dual x-ray absorptiometry at the lumbar spine, femoral neck and the radius. Serum bone formation and bone resorption markers (osteocalcin and beta-crosslaps, respectively) were measured using immunoassays. Low bone mass was measured in 57.14% patients with microscopic colitis. Bone mineral density at the femoral neck in patients suffering from microscopic colitis and Crohn's disease was lower than in healthy controls (0.852 ± 0.165 and 0.807 ± 0.136 vs. 1.056 ± 0.126 g/cm²; p microscopic colitis patients (0.565 ± 0.093 vs. 0.667 ± 0.072 g/cm²; p microscopic colitis and Crohn's disease patients than controls (417.714 ± 250.37 and 466.071 ± 249.96 vs. 264.75 ± 138.65 pg/ml; p microscopic colitis patients. Low bone mass is frequent in microscopic colitis, and alterations to bone metabolism are similar to those present in Crohn's disease. Therefore, microscopic colitis-associated osteopenia could be a significant problem in such patients.

  15. Stercoral colitis complicated with ischemic colitis: a double-edge sword.

    Science.gov (United States)

    Naseer, Maliha; Gandhi, Jenil; Chams, Noor; Kulairi, Zain

    2017-11-28

    Stercoral colitis is a rare inflammatory process involving the colonic wall secondary to fecal impaction with high morbidity and mortality; especially if complicated with ischemic colitis, stercoral ulcer formation and subsequent perforation. There are several case reports published on abdominal perforation resulting from stercoral colitis. However, stercoral colitis complicated by ischemic colitis is rare. The purpose of this case report is to describe the potential challenges in the diagnosis and management of stercoral colitis with ischemic colitis. An 87 years old male with history of chronic constipation presents with severe abdominal pain to the emergency department. The patient was hemodynamically stable. On physical examination, the abdomen was mildly distended with moderate tenderness. Lab work was significant for leukocytosis and lactic acidosis. Abdominal CT scan revealed large amount of retained stool in the colon, bowel wall thickening and infiltration of peri-colonic fat, which were suggestive for stercoral colitis. Patient was started on IV fluids and antibiotics. He was given an enema, followed by laxative and manual disimpaction of stool. Colonoscopy was performed and biopsies were obtained. Tissue biopsy was significant for focal active colitis with regenerative glandular changes and neural hyperplasia. Elevated lactic acid level secondary to ischemia of the bowel wall with CT scan findings aid in establishing the diagnosis of stercoral colitis complicated with ischemic colitis. Urgent treatment with laxatives and fecal disimpaction is indicated to prevent perforation and peritonitis.

  16. Evolution of microscopic colitis to giant cell colitis without significant intraepithelial lymphocytosis or thickened collagen plate.

    Science.gov (United States)

    De Petris, Giovanni; Chen, Longwen

    2015-05-01

    Microscopic colitis (MC) is an umbrella term that encompasses lymphocytic colitis (LC) and collagenous colitis (CC). Several histological variants of these 2 entities exist; among them is the uncommon giant cell colitis (GCC), in which histiocytic giant cells (GCs) are present in background of CC or LC. We report the case of a 71-year-old woman complaining of watery diarrhea for several years that was diagnosed with CC. At follow-up, she developed giant cell colitis (GCC). Nine years later, a colectomy revealed a form of microscopic colitis in which significant intraepithelial lymphocytosis and collagen plate thickening have disappeared while GCs persisted with diffuse mononuclear cells inflammation of the lamina propria. Thinning of the collagen plate in association with GCs has been described previously. The case contributes the possibility of further evolution of MC into a pure giant cell colitis in which the prototypical manifestations of MC have all but disappeared. © The Author(s) 2014.

  17. Microscopic colitis : an unfamiliar but treatable disease

    NARCIS (Netherlands)

    van der Wouden, E. J.; Karrenbeld, A.; Kleibeuker, J. H.; Dijkstra, G.

    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

  18. Experimental effects of exposure to pornography: the moderating effect of personality and mediating effect of sexual arousal.

    Science.gov (United States)

    Hald, Gert Martin; Malamuth, Neil N

    2015-01-01

    Using a randomly selected community sample of 200 Danish young adult men and women in a randomized experimental design, the study investigated the effects of a personality trait (agreeableness), past pornography consumption, and experimental exposure to non-violent pornography on attitudes supporting violence against women (ASV). We found that lower levels of agreeableness and higher levels of past pornography consumption significantly predicted ASV. In addition, experimental exposure to pornography increased ASV but only among men low in agreeableness. This relationship was found to be significantly mediated by sexual arousal with sexual arousal referring to the subjective assessment of feeling sexually excited, ready for sexual activities, and/or bodily sensations associated with being sexually aroused. In underscoring the importance of individual differences, the results supported the hierarchical confluence model of sexual aggression and the media literature on affective engagement and priming effects.

  19. The Potential Protective Role of Caveolin-1 in Intestinal Inflammation in TNBS-Induced Murine Colitis

    Science.gov (United States)

    Ma, Yanbing; Qing, Gefei; Bernstein, Charles N.; Warrington, Richard J.; Peng, Zhikang

    2015-01-01

    Background Caveolin-1 (Cav-1) is a multifunctional scaffolding protein serving as a platform for the cell’s signal-transduction and playing an important role in inflammation. However, its role in inflammatory bowel disease is not clear. A recent study showed that Cav-1 is increased and mediates angiogenesis in dextran sodium sulphate-induced colitis, which are contradictory to our pilot findings in 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis. In the present study, we further clarified the role of Cav-1 in TNBS-induced colitis. Methods In BALB/c mice, acute colitis was induced by intra-rectal administration of one dose TNBS, while chronic colitis was induced by administration of TNBS once a week for 7 weeks. To assess the effects of complete loss of Cav-1, Cav-1 knockout (Cav-1−/−) and control wild-type C57 mice received one TNBS administration. Body weight and clinical scores were monitored. Colon Cav-1 and pro-inflammatory cytokine levels were quantified through ELISAs. Inflammation was evaluated through histological analysis. Results Colon Cav-1 levels were significantly decreased in TNBS-induced colitis mice when compared to normal mice and also inversely correlated with colon inflammation scores and proinflammatory cytokine levels (IL-17, IFN-γ and TNF) significantly. Furthermore, after administration of TNBS, Cav-1−/− mice showed significantly increased clinical and colon inflammatory scores and body weight loss when compared with control mice. Conclusions and Significance Cav-1 may play a protective role in the development of TNBS-induced colitis. Our findings raise an important issue in the evaluation of specific molecules in animal models that different models may exhibit opposite results because of the different mechanisms involved. PMID:25756273

  20. 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....

  1. Microscopic colitis: is it a spectrum of inflammatory bowel disease?

    Science.gov (United States)

    Jegadeesan, Ramprasad; Liu, Xiuli; Pagadala, Mangesh R; Gutierrez, Norma; Butt, Mujtaba; Navaneethan, Udayakumar

    2013-07-14

    Lymphocytic and collagenous colitis are forms of microscopic colitis which typically presents in elderly patients as chronic watery diarrhea. The association between microscopic colitis and inflammatory bowel disease is weak and unclear. Lymphocytic colitis progressing to ulcerative colitis has been previously reported; however there is limited data on ulcerative colitis evolving into microscopic (lymphocytic or collagenous) colitis. We report a series of six patients with documented ulcerative colitis who subsequently were diagnosed with collagenous colitis or lymphocytic colitis suggesting microscopic colitis could be a part of the spectrum of inflammatory bowel disease. The median duration of ulcerative colitis prior to being diagnosed with microscopic colitis was 15 years. We noted complete histological and/or symptomatic remission in three out of six cases while the other three patients reverted back into ulcerative colitis suggesting lymphocytic or collagenous colitis could present as a continuum of ulcerative colitis. The exact molecular mechanism of this histological transformation or the prognostic implications is still unclear. Till then it might be prudent to follow up these patients to assess for the relapse of inflammatory bowel disease as well as for dysplasia surveillance.

  2. Role and species–specific expression of colon T cell homing receptor GPR15 in colitis

    Science.gov (United States)

    Nguyen, Linh P.; Pan, Junliang; Dinh, Theresa Thanh; Hadeiba, Husein; O’Hara, Edward; Ebtikar, Ahmad; Hertweck, Arnulf; Gökmen, M. Refik; Lord, Graham M.; Jenner, Richard G.

    2014-01-01

    Lymphocyte recruitment maintains intestinal immune homeostasis but also contributes to inflammation. The orphan chemoattractant receptor GPR15 mediates regulatory T cell homing and immunosuppression in the mouse colon. We show that GPR15 is also expressed by mouse TH17 and TH1 effector cells, and is required for colitis in a model that depends on their trafficking to the colon. In humans GPR15 is expressed by effector cells including pathogenic TH2 cells in ulcerative colitis, but is not expressed by regulatory T (Treg) cells. The TH2 transcriptional activator GATA-3 and the Treg–associated transcriptional repressor FOXP3 robustly bind human, but not mouse, GPR15 enhancer sequences, correlating with expression. Our results highlight species differences in GPR15 regulation, and suggest it as a potential therapeutic target for colitis. PMID:25531831

  3. Medicinal Plants in the Treatment of Colitis: Evidence from Preclinical Studies.

    Science.gov (United States)

    Santana, Marília T; Cercato, Luana M; Oliveira, Janaíne P; Camargo, Enilton A

    2017-05-01

    Ulcerative colitis is a chronic inflammatory condition whose treatment includes aminosalicylates, corticosteroids, and immunomodulators. Medicinal plants seem to be an important alternative treatment for this condition. They have been the subject of a great number of studies in recent years. This study was conducted to systematically review the medicinal plants tested in experimental models of ulcerative colitis. We conducted a systematic literature search through specialized databases (PUBMED, SCOPUS, EMBASE, MEDLINE, LILACS, SCIELO, and SCISEARCH) and selected articles published between January 2000 and June 21, 2016 by using "medicinal plants" and "ulcerative colitis" as key words. Sixty-eight studies were included, and the families Asteraceae and Lamiaceae presented the largest number of studies, but plants from several other families were cited; many of them have shown good results in experimental animals. However, only a few species (such as Andrographis paniculata and Punica granatum) have undergone clinical tests against ulcerative colitis, and the observation that many preclinical studies reviewed are purely descriptive has certainly contributed to this fact. Chemical constituents (mainly flavonoids and terpenes) seem to play a role in the effects of the plants. Thus, the data herein reviewed reinforce the potential of medicinal plants as a source of alternative approaches to the treatment of ulcerative colitis. Georg Thieme Verlag KG Stuttgart · New York.

  4. Strongyloides colitis is a lethal mimic of ulcerative colitis: the key morphologic differential diagnosis.

    Science.gov (United States)

    Qu, Zhenhong; Kundu, Uma R; Abadeer, Rania A; Wanger, Audrey

    2009-04-01

    Strongyloides stercoralis colitis is a severe, but easily curable, form of strongyloidiasis that carries a high mortality rate if untreated. Autoinfection characteristic of Strongyloides stercoralis frequently makes the infection a life-long disease unless it is effectively treated. Our experience with 4 cases of Strongyloides colitis prompted us to assess the clinical outcome of the disease by literature review. In this case series, the misdiagnosis and resultant mortality rates of Strongyloides colitis are 52% and 39.1%, respectively. A low index of suspicion and morphologic resemblance to ulcerative colitis were the main sources of diagnostic error. Ulcerative colitis alone accounted for 38.5% of the erroneous diagnoses. Features of Strongyloides colitis that contrast with those of ulcerative colitis include (1) skip pattern of the inflammation, (2) distal attenuation of the disease, (3) eosinophil-rich infiltrates, (4) relative intact crypt architecture, and (5) frequent involvement of submucosa. We also found that history of steroid therapy, chronic colitis refractory to conventional immune-modifying management, and endoscopic finding of distal attenuation of the colitis are helpful clues. It is also our experience that if Strongyloides colitis is included in the differential diagnosis, the correct diagnosis can usually be made. Current therapy with ivermectin or albendazole is very effective at a cure rate greater than 98%. We believe that the misdiagnosis and mortality rates of this curable, but often, unnecessarily deadly, infectious disease are alarming and warrant efforts to increase the awareness of the disease.

  5. Review article: Microscopic colitis--lymphocytic, collagenous and 'mast cell' colitis.

    Science.gov (United States)

    Yen, E F; Pardi, D S

    2011-07-01

    Microscopic colitis is a relatively common cause of chronic diarrhoea in predominantly older adults, traditionally termed lymphocytic colitis and collagenous colitis. Increased mast cells found in the colonic biopsies of some patients with chronic diarrhoea may represent a distinct type of microscopic colitis. To provide an updated review of the epidemiology, diagnosis and treatment of microscopic colitis, and to discuss the role of mast cells in the gastrointestinal tract and their potential role in cases of functional diarrhoea. A MEDLINE literature search was performed to identify pertinent articles. Relevant clinical abstracts were also reviewed. Incidence rates of microscopic colitis (lymphocytic and collagenous colitis) have increased over time, to levels comparable with other forms of inflammatory bowel disease. The possibility of drug-induced microscopic colitis and concomitant coeliac sprue are important considerations when evaluating these patients. There are few controlled treatment trials in microscopic colitis, with much of the data on treatment coming from retrospective studies. Mast cells have been implicated in functional bowel disorders, with increased mast cells possibly contributing to cases of otherwise unexplained chronic diarrhoea, although this concept requires further investigation. In patients with microscopic colitis, a systematic approach to therapy often leads to satisfactory control of symptoms. The role of mast cells in chronic diarrhoea represents an evolving field, with the potential to offer alternative treatment pathways in patients with otherwise unexplained functional diarrhoea. © 2011 Blackwell Publishing Ltd.

  6. Preventive effects of Goji berry on dextran-sulfate-sodium-induced colitis in mice.

    Science.gov (United States)

    Kang, Yifei; Xue, Yansong; Du, Min; Zhu, Mei-Jun

    2017-02-01

    Goji berry (Lycium barbarum) exerts immune modulation and suppresses inflammation in vitro and in vivo. We hypothesized that Goji berry had beneficial effects on dextran sulfate sodium (DSS)-induced colitis in C57BL/6 mice through suppressing inflammation. Six-week-old male C57BL/6 mice were supplemented with a standard AIN-93G diet with or without 1% (w/w) Goji berry for 4 weeks. Then, colitis was induced by supplementing 3% DSS in drinking water for 7 days, followed by 7 days of remission period to mimic ulcerative colitis symptoms. Goji berry supplementation ameliorated DSS-induced body weight loss, diminished diarrhea and gross bleeding, and resulted in a significantly decreased disease activity index, as well as DSS-associated colon shortening. Moreover, 30% mortality rate caused by DSS-induced colitis was avoided because of Goji berry supplementation. Histologically, Goji berry ameliorated colonic edema, mucosal damage and neutrophil infiltration into colonic intestinal tissue in response to DSS challenge, which was associated with decreased expression of chemokine (C-X-C motif) ligand 1 and monocyte chemoattractant protein-1, as well as inflammatory mediators interleukin-6 and cyclooxygenase-2. In conclusion, Goji supplementation confers protective effects against DSS-induced colitis, which is associated with decreased neutrophil infiltration and suppressed inflammation. Thus, dietary Goji is likely beneficial to inflammatory bowel disease patients as a complementary therapeutic strategy. Published by Elsevier Inc.

  7. Facilitating the Acquisition of Sensorimotor Behavior with a Microcomputer-Mediated Teaching System: An Experimental Analysis.

    Science.gov (United States)

    Horn, Eva M.; Warren, Steven F.

    1987-01-01

    The effects of a combined neuromotor/behavioral approach using a microcomputer mediated teaching system on the acquisition of basic motor skills by two young children (17- and 24-months-old) with severe and multiple disabilities were examined. Increased frequency and duration of target behaviors in both training and generalizing settings were…

  8. The mechanism of Zinc(II)-Mediated Vulcanization Uncovered; Theoretical and Experimental Evidence.

    NARCIS (Netherlands)

    Nieuwenhuizen, P.J.; Ehlers, A.W.; Haasnoot, J.G.; Janse, S.R.; Reedijk, J.; Baerends, E.J.

    1999-01-01

    The mechanism of cross-link formation in sulfur vulcanization mediated by bis(dimethyldithiocarbamato)zinc(II), ZDMC, has been uncovered, utilizing a combination of Density-Functional calculations and model experiments. These studies have revealed that, in a three-stage process, ZDMC exhibits a

  9. Mediators' Emotional Responses to Self-Injurious Behavior: An Experimental Study.

    Science.gov (United States)

    Mossman, Dominique A.; Hastings, Richard P.; Brown, Tony

    2002-01-01

    Sixty mediators from British schools for children with mental retardation watched one of five matched videos depicting no self-injury, self-injury maintained by positive reinforcement, self-injury maintained by negative reinforcement, and self-injury unrelated to social events. Self-injury maintained by negative reinforcement was associated with…

  10. Sphingomyelin synthase 2 deficiency inhibits the induction of murine colitis-associated colon cancer.

    Science.gov (United States)

    Ohnishi, Toshio; Hashizume, Chieko; Taniguchi, Makoto; Furumoto, Hidehiro; Han, Jia; Gao, Rongfen; Kinami, Shinichi; Kosaka, Takeo; Okazaki, Toshiro

    2017-09-01

    Sphingomyelin synthase 2 (SMS2) is the synthetic enzyme of sphingomyelin (SM), which regulates membrane fluidity and microdomain structure. SMS2 plays a role in LPS-induced lung injury and inflammation; however, its role in inflammation-mediated tumorigenesis is unclear. We investigated the effect of SMS2 deficiency on dextran sodium sulfate (DSS)-induced murine colitis and found inhibition of DSS-induced inflammation in SMS2-deficient (SMS2-/-) mice. DSS treatment induced a significant increase in ceramide levels, with a decrease of SM levels in SMS2-/- colon tissue, and demonstrated attenuation of the elevation of both inflammation-related gene expression and proinflammatory cytokines and chemokines, leukocyte infiltration, and MAPK and signal transducer and activator of transcription 3 activation. After undergoing transplantation of wild-type bone marrow, SMS2-/- mice also exhibited inhibition of DSS-induced inflammation in the colon, which suggested that SMS2 deficiency in bone marrow-derived immune cells was not involved in the inhibition of colitis. Finally, in an azoxymethane/DSS-induced cancer model, SMS2 deficiency significantly decreased tumor incidence in the colon. Our results demonstrate that SMS2 deficiency inhibits DSS-induced colitis and subsequent colitis-associated colon cancer via inhibition of colon epithelial cell-mediated inflammation; therefore, inhibition of SMS2 may be a potential therapeutic target for human colitis and colorectal cancer.-Ohnishi, T., Hashizume, C., Taniguchi, M., Furumoto, H., Han, J., Gao, R., Kinami, S., Kosaka, T., Okazaki, T. Sphingomyelin synthase 2 deficiency inhibits the induction of murine colitis-associated colon cancer. © FASEB.

  11. Sulphasalazine-Induced Pseudomembranous Colitis

    Directory of Open Access Journals (Sweden)

    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.

  12. 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...... epithelial cells and other cells of the mucosa are discussed. The biochemistry of wound healing in UC provides the basis for the subsequent description of how these pathways are affected by the current medications, and what can be learnt on how to design future treatment regimens for UC based on targeting...

  13. Microscopic colitis: A review of etiology, treatment and refractory disease

    OpenAIRE

    Park, Tina; Cave, David; Marshall, Christopher

    2015-01-01

    Microscopic colitis is a common cause of chronic, nonbloody diarrhea. Microscopic colitis is more common in women than men and usually affects patients in their sixth and seventh decade. This article reviews the etiology and medical management of microscopic colitis. The etiology of microscopic colitis is unknown, but it is associated with autoimmune disorders, such as celiac disease, polyarthritis, and thyroid disorders. Smoking has been identified as a risk factor of microscopic colitis. Ex...

  14. Endothelin-1 Mediates Brain Microvascular Dysfunction Leading to Long-Term Cognitive Impairment in a Model of Experimental Cerebral Malaria.

    Directory of Open Access Journals (Sweden)

    Brandi D Freeman

    2016-03-01

    Full Text Available Plasmodium falciparum infection causes a wide spectrum of diseases, including cerebral malaria, a potentially life-threatening encephalopathy. Vasculopathy is thought to contribute to cerebral malaria pathogenesis. The vasoactive compound endothelin-1, a key participant in many inflammatory processes, likely mediates vascular and cognitive dysfunctions in cerebral malaria. We previously demonstrated that C57BL6 mice infected with P. berghei ANKA, our fatal experimental cerebral malaria model, sustained memory loss. Herein, we demonstrate that an endothelin type A receptor (ETA antagonist prevented experimental cerebral malaria-induced neurocognitive impairments and improved survival. ETA antagonism prevented blood-brain barrier disruption and cerebral vasoconstriction during experimental cerebral malaria, and reduced brain endothelial activation, diminishing brain microvascular congestion. Furthermore, exogenous endothelin-1 administration to P. berghei NK65-infected mice, a model generally regarded as a non-cerebral malaria negative control for P. berghei ANKA infection, led to experimental cerebral malaria-like memory deficits. Our data indicate that endothelin-1 is critical in the development of cerebrovascular and cognitive impairments with experimental cerebral malaria. This vasoactive peptide may thus serve as a potential target for adjunctive therapy in the management of cerebral malaria.

  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

    with 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......, 50 and 75 ml/min coefficient of variation 21%; n = 6). In patients with ulcerative colitis, colonic output of NO was 10-fold higher (P collagenous colitis, colonic output of NO was 50-fold...... for quantification of colonic mucosal NO production. Increased colonic production of NO in collagenous colitis, which exceeds the output observed even in extensive ulcerative colitis, militates against the theory that NO per se is a cause of mucosal injury....

  16. Low bone mass in microscopic colitis

    Directory of Open Access Journals (Sweden)

    Lakatos Péter

    2011-05-01

    Full Text Available Abstract Background Microscopic colitis presents with similar symptoms to classic inflammatory bowel diseases. Osteoporosis is a common complication of Crohn's disease but there are no data concerning bone metabolism in microscopic colitis. Aims The aim of the present study was to evaluate bone density and metabolism in patients with microscopic colitis. Methods Fourteen patients microscopic colitis were included in the study, and 28 healthy persons and 28 age and gender matched Crohn's disease patients were enrolled as controls. Bone mineral density was measured using dual x-ray absorptiometry at the lumbar spine, femoral neck and the radius. Serum bone formation and bone resorption markers (osteocalcin and beta-crosslaps, respectively were measured using immunoassays. Results Low bone mass was measured in 57.14% patients with microscopic colitis. Bone mineral density at the femoral neck in patients suffering from microscopic colitis and Crohn's disease was lower than in healthy controls (0.852 ± 0.165 and 0.807 ± 0.136 vs. 1.056 ± 0.126 g/cm2; p 2; p 2. Mean beta-crosslaps concentration was higher in microscopic colitis and Crohn's disease patients than controls (417.714 ± 250.37 and 466.071 ± 249.96 vs. 264.75 ± 138.65 pg/ml; p Conclusions Low bone mass is frequent in microscopic colitis, and alterations to bone metabolism are similar to those present in Crohn's disease. Therefore, microscopic colitis-associated osteopenia could be a significant problem in such patients.

  17. Surgical management of ulcerative colitis.

    Science.gov (United States)

    Bennis, Malika; Tiret, Emmanuel

    2012-01-01

    Surgery is the only curative option in the treatment of ulcerative colitis. Despite advances in the medical management surgery is required in about a third of patients. In the acute setting surgery is indicated when medical treatment fails to improve an episode of acute severe colitis. The intervention of choice is a staged colectomy with end ileostomy and preservation of the rectal stump in the first instance. Indications for elective surgery are failure of medical therapy and malignant transformation. The surgical options include conventional proctectomy with ileostomy or a Kock's continent ileostomy and colectomy with an ileorectal anastomosis. The current gold standard is restorative proctocolectomy with ileal pouch-anal anastomosis. Most frequently the technique includes a J pouch with a stapled anastomosis and temporary faecal diversion with a loop ileostomy. Laparoscopic pouch surgery is a feasible and safe option with an excellent cosmetic result. Although the morbidity remains significant after surgery, the quality of life is good with a satisfactory long-term functional outcome.

  18. Intestinal anti-inflammatory activity of ellagic acid in the acute and chronic dextrane sulfate sodium models of mice colitis.

    Science.gov (United States)

    Marín, Marta; María Giner, Rosa; Ríos, José-Luis; Recio, María Carmen

    2013-12-12

    Pomegranate (Punica granatum L.; Lythraceae) has traditionally been used for the treatment of various inflammatory diseases, including ulcerative colitis (UC). Because its fruits and extracts are rich in ellagitannins, which release ellagic acid when hydrolyzed, consumption of pomegranate products is currently being widely promoted for their potential health effects, including the prevention of inflammatory diseases and cancer. To evaluate the anti-inflammatory effects of ellagic acid on dextran sulfate sodium (DSS)-induced acute and chronic experimental colitis in two different strains of mice and to elucidate its possible mechanisms of action. In the acute UC model, female Balb/C mice were treated with DSS (5%) for seven days while concomitantly receiving a dietary supplement of ellagic acid (2%). In the chronic UC model, female C57BL/6 mice received four week-long cycles of DSS (1% and 2%) interspersed with week-long recovery periods along with a diet supplemented with ellagic acid (0.5%). In acute model of UC, ellagic acid ameliorated disease severity slightly as observed both macroscopically and through the profile of inflammatory mediators (IL-6, TNF-α, and IFN-γ). In the chronic UC model, ellagic acid significantly inhibited the progression of the disease, reducing intestinal inflammation and decreasing histological scores. Moreover, mediators such as COX-2 and iNOS were downregulated and the signaling pathways p38 MAPK, NF-κB, and STAT3 were blocked. Our study reinforces the hypothetical use of ellagic acid as an anti-inflammatory complement to conventional UC treatment in chronic UC patients and could be considered in the dietary prevention of intestinal inflammation and related cancer development. © 2013 Published by Elsevier Ireland Ltd.

  19. α7 Nicotinic Agonist AR-R17779 Protects Mice against 2,4,6-Trinitrobenzene Sulfonic Acid-Induced Colitis in a Spleen-Dependent Way

    Directory of Open Access Journals (Sweden)

    Andrea Grandi

    2017-11-01

    Full Text Available The existence of a cholinergic anti-inflammatory pathway negatively modulating the inflammatory and immune responses in various clinical conditions and experimental models has long been postulated. In particular, the protective involvement of the vagus nerve and of nicotinic Ach receptors (nAChRs has been proposed in intestinal inflammation and repeatedly investigated in DSS- and TNBS-induced colitis. However, the role of α7 nAChRs stimulation is still controversial and the potential contribution of α4β2 nAChRs has never been explored in this experimental condition. Our aims were therefore to pharmacologically investigate the role played by both α7 and α4β2 nAChRs in the modulation of the local and systemic inflammatory responses activated in TNBS-induced colitis in mice and to assess the involvement of the spleen in nicotinic responses. To this end, TNBS-exposed mice were sub-acutely treated with various subcutaneous doses of highly selective agonists (AR-R17779 and TC-2403 and antagonists (methyllycaconitine and dihydro-β-erythroidine of α7 and α4β2 nAChRs, respectively, or with sulfasalazine 50 mg/kg per os and clinical and inflammatory responses were evaluated by means of biochemical, histological and flow cytometry assays. α4β2 ligands evoked weak and contradictory effects, while α7 nAChR agonist AR-R17779 emerged as the most beneficial treatment, able to attenuate several local markers of colitis severity and to revert the rise in splenic T-cells and in colonic inflammatory cytokines levels induced by haptenization. After splenectomy, AR-R17779 lost its protective effects, demonstrating for the first time that, in TNBS-model of experimental colitis, the anti-inflammatory effect of exogenous α7 nAChR stimulation is strictly spleen-dependent. Our findings showed that the selective α7 nAChRs agonist AR-R17779 exerted beneficial effects in a model of intestinal inflammation characterized by activation of the adaptive immune

  20. 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.

  1. Pseudomembranous colitis in a pregnant woman.

    Science.gov (United States)

    Mridula, T; Pai, R R; Mathai, A M; Tantry, B V; Adhikari, P

    2010-01-01

    Pseudomembranous colitis in association with pregnancy has not been well described in English literature. Recent studies show a drastic increase in the incidence and severity of Pseudomembranous colitis in pregnant women, who were once thought to be at low risk. We report here a case of Pseudomembranous colitis in a young healthy immunocompetent pregnant lady. An early suspicion of this entity with the characteristic appearance of pseudomembranes on colonoscopy and histology confirmed the diagnosis enabling prompt treatment and complete recovery without any serious consequences.

  2. CT pseudomembranous colitis. Computertomographie bei pseudomembranoeser Kolitis

    Energy Technology Data Exchange (ETDEWEB)

    Gaa, J. (Heidelberg Univ., Klinikum Mannheim, Inst. fuer Klinische Radiologie (Germany)); Lee, M.J. (Massachusetts General Hospital, Boston, MA (United States). Dept. of Gastrointestinal Radiology); Georgi, M. (Heidelberg Univ., Klinikum Mannheim, Inst. fuer Klinische Radiologie (Germany))

    1993-09-01

    Pseudomembranous colitis (PMC) is an infectious colitis usually occurring as a complication of antibiotic therapy. The computed tomography (CT) findings of 10 patients with PMC are reviewed. All patients demonstrated an abnormal large bowel wall with an average thickness of 13 mm (range 7-31 mm). Additional, but less frequent findings included mesenteric inflammation, ascites, pleural effusions, and dilatation of the large or small bowel. Pancolonic involvement was seen in 7 cases, while three patients had focal colitis. Although the CT appearance of PMC is not specific, the diagnosis may be suggested in the proper clinical setting. (orig.)

  3. The pseudomembranous colitis associated with clindamycin therapy--a viral colitis.

    Science.gov (United States)

    Steer, H W

    1975-01-01

    Four patients are described who developed pseudomembranous colitis in association with clindamycin therapy. Rectal biopsies from two patients were studied with the electron microscope and compared with the ultrastructural appearance of the rectal mucosa from seven normal people. Ultrastructural evidence for a viral colitis was obtained. The significance of the clindamycin therapy to the viral colitis and the contribution of the viral colitis to the clinical state are discussed. Images Fig 2 Fig 3 Fig 4 Fig 5 Fig 6 Fig 7 Fig 8 Fig 9 Fig 10 Fig 11 Fig 12 Fig 13 Fig 14 PMID:1193426

  4. Soluble Mediators in Platelet Concentrates Modulate Dendritic Cell Inflammatory Responses in an Experimental Model of Transfusion.

    Science.gov (United States)

    Perros, Alexis J; Christensen, Anne-Marie; Flower, Robert L; Dean, Melinda M

    2015-10-01

    The transfusion of platelet concentrates (PCs) is widely used to treat thrombocytopenia and severe trauma. Ex vivo storage of PCs is associated with a storage lesion characterized by partial platelet activation and the release of soluble mediators, such as soluble CD40 ligand (sCD40L), RANTES, and interleukin (IL)-8. An in vitro whole blood culture transfusion model was employed to assess whether mediators present in PC supernatants (PC-SNs) modulated dendritic cell (DC)-specific inflammatory responses (intracellular staining) and the overall inflammatory response (cytometric bead array). Lipopolysaccharide (LPS) was included in parallel cultures to model the impact of PC-SNs on cell responses following toll-like receptor-mediated pathogen recognition. The impact of both the PC dose (10%, 25%) and ex vivo storage period was investigated [day 2 (D2), day 5 (D5), day 7 (D7)]. PC-SNs alone had minimal impact on DC-specific inflammatory responses and the overall inflammatory response. However, in the presence of LPS, exposure to PC-SNs resulted in a significant dose-associated suppression of the production of DC IL-12, IL-6, IL-1α, tumor necrosis factor-α (TNF-α), and macrophage inflammatory protein (MIP)-1β and storage-associated suppression of the production of DC IL-10, TNF-α, and IL-8. For the overall inflammatory response, IL-6, TNF-α, MIP-1α, MIP-1β, and inflammatory protein (IP)-10 were significantly suppressed and IL-8, IL-10, and IL-1β significantly increased following exposure to PC-SNs in the presence of LPS. These data suggest that soluble mediators present in PCs significantly suppress DC function and modulate the overall inflammatory response, particularly in the presence of an infectious stimulus. Given the central role of DCs in the initiation and regulation of the immune response, these results suggest that modulation of the DC inflammatory profile is a probable mechanism contributing to transfusion-related complications.

  5. 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.

  6. Nitric oxide increases Wnt-induced secreted protein-1 (WISP-1/CCN4) expression and function in colitis.

    Science.gov (United States)

    Wang, Hongying; Zhang, Rui; Wen, Shoubin; McCafferty, Donna-Marie; Beck, Paul L; MacNaughton, Wallace K

    2009-04-01

    Nitric oxide (NO) derived from the inducible NO synthase (iNOS) is an important and complex mediator of inflammation in the intestine. Wnt-inducible secreted protein (WISP)-1 (CCN4), a member of the connective tissue growth factor family, is involved in tissue repair. We sought to determine the relationship between iNOS and WISP-1 in colitis. By analyzing human colonic biopsy samples, we showed that the expression of mRNA for both iNOS and WISP-1 was significantly higher in ulcerative colitis samples compared with control tissue. The upregulation of WISP-1 was positively correlated with iNOS expression in two models of colitis, induced by intrarectal trinitrobenzenesulfonic acid (TNBS) or occurring spontaneously in IL-10 deficient mice. Loss of iNOS, studied using iNOS(-/-) mice in both TNBS-induced and IL-10(-/-) colitis models, significantly attenuated the colitis-related WISP-1 increase. In human colonic epithelial cell lines, the NO donor, DETA-NONOate, elevated WISP-1 mRNA and protein expression through a beta-catenin and CREB-dependent, but Wnt-1-independent, pathway. In addition, NO-induced WISP-1 directly induced secretion of soluble collagen in colonic fibroblast cells. NO increases WISP-1 expression both in vitro and in vivo, suggesting a new role for iNOS and NO in colitis.

  7. Effects of jujube fruit extract on acetic acid‑induced colitis in adult ...

    African Journals Online (AJOL)

    Background: Gut health is the most important factor for a healthy life. A large number of people are suffering from gut associated diseases. Inflammatory bowel disease is the general medical terminology for chronic inflammatory illness of unknown origin. Experimental colitis induced by acetic acid has been used extensively ...

  8. Changes in Gingival Crevicular Fluid Inflammatory Mediator Levels during the Induction and Resolution of Experimental Gingivitis in Humans

    Science.gov (United States)

    Offenbacher, Steven; Barros, Silvana; Mendoza, L; Mauriello, S; Preisser, J; Moss, K; de Jager, Marko; Aspiras, Marcelo

    2010-01-01

    Aim The goal of this study is to characterize the changes in 33 biomarkers within the gingival crevicular fluid during the 3-week induction and 4-week resolution of stent-induced, biofilm overgrowth mediated, experimental gingivitis in humans. Methods Experimental gingivitis was induced in 25 subjects for 21 days followed by treatment with a sonic powered toothbrush for 28 days. Clinical indices and gingival crevicular fluids were collected weekly during induction and biweekly during resolution. Samples were analyzed using a bead-based multiplexing analysis for the simultaneous measurements of 33 biomarkers within each sample including cytokines, matrix-metalloproteinases and adipokines. Prostaglandin-E2 was measured by enzyme-linked immunoadsorbant assay. Statistical testing using general linear models with structured covariance matrices were performed to compare stent to contralateral (non-stent) changes in clinical signs and in biomarker levels over time. Results Gingivitis induction was associated with a significant 2.6-fold increase in interleukin 1-beta, a 3.1 fold increase in interleukin 1-alpha, and a significant decrease in multiple chemokines as well as matrixmetalloproteinases −1, −3 and 13. All changes in clinical signs and mediators rebounded to baseline in response to treatmentin the resolution phase. Conclusions Stent-induced gingivitis is associated with marked, but reversible increases in interleukins 1-alpha and 1-beta with suppression of multiple chemokines as well as selected matrixmetalloproteinases. PMID:20447255

  9. 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.

  10. The experimental study of genetic engineering human neural stem cells mediated by lentivirus to express multigene.

    Science.gov (United States)

    Cai, Pei-qiang; Tang, Xun; Lin, Yue-qiu; Martin, Oudega; Sun, Guang-yun; Xu, Lin; Yang, Yun-kang; Zhou, Tian-hua

    2006-02-01

    To explore the feasibility to construct genetic engineering human neural stem cells (hNSCs) mediated by lentivirus to express multigene in order to provide a graft source for further studies of spinal cord injury (SCI). Human neural stem cells from the brain cortex of human abortus were isolated and cultured, then gene was modified by lentivirus to express both green fluorescence protein (GFP) and rat neurotrophin-3 (NT-3); the transgenic expression was detected by the methods of fluorescence microscope, dorsal root ganglion of fetal rats and slot blot. Genetic engineering hNSCs were successfully constructed. All of the genetic engineering hNSCs which expressed bright green fluorescence were observed under the fluorescence microscope. The conditioned medium of transgenic hNSCs could induce neurite flourishing outgrowth from dorsal root ganglion (DRG). The genetic engineering hNSCs expressed high level NT-3 which could be detected by using slot blot. Genetic engineering hNSCs mediated by lentivirus can be constructed to express multigene successfully.

  11. Impact of stress on paranoia: an experimental investigation of moderators and mediators.

    Science.gov (United States)

    Lincoln, T M; Peter, N; Schäfer, M; Moritz, S

    2009-07-01

    Vulnerability-stress models ascribe stress a pivotal role in the development of psychosis. However, moderating and mediating mechanisms translating stress into psychosis and the specificity of the association are not clearly established. It is hypothesized that stress will trigger paranoid ideation in vulnerable individuals through an increase in negative emotion. Using a repeated-measures design, 64 healthy participants with varying levels of vulnerability [psychosis symptoms assessed by the Community Assessment of Psychic Experiences (CAPE)] were assigned to a stress and a non-stress condition in random order. Stress was induced by exposing participants to building-site noise (75 dB) applied concurrently with difficult knowledge questions. Symptoms of paranoia, depression and obsessive compulsive disorder (OCD) were assessed by state-adapted versions of clinical scales. In the stress condition there was an increase in paranoia, depression and negative emotion. Multilevel linear modeling (MLM) revealed the increase in paranoia under stress to be moderated by the level of vulnerability and mediated by anxiety. Although participants generally showed an increase in anxiety under stress, anxiety was more strongly related to paranoia in participants with higher baseline symptomatology. The results support and specify the role of emotional reactions to stressors on the pathway from vulnerability to psychosis and highlight the relevance of anxiety.

  12. Protective Role of Cyclooxygenase (COX)-2 in Experimental Lung Injury: Evidence of a Lipoxin A(4)-Mediated Effect.

    LENUS (Irish Health Repository)

    2012-02-01

    BACKGROUND: Polymorphoneutrophils (PMNs) are activated by inflammatory mediators following splanchnic ischemia\\/reperfusion (I\\/R), potentially injuring organs such as the lung. As a result, some patients develop respiratory failure following abdominal aortic aneurysm repair. Pulmonary cyclooxygenase (COX)-2 protects against acid aspiration and bacterial instillation via lipoxins, a family of potent anti-inflammatory lipid mediators. We explored the role of COX-2 and lipoxin A(4) in experimental I\\/R-mediated lung injury. MATERIALS AND METHODS: Sprague-Dawley rats were assigned to one of the following five groups: (1) controls; (2) aortic cross-clamping for 45 min and reperfusion for 4 h (I\\/R group); (3) I\\/R and SC236, a selective COX-2 inhibitor; (4) I\\/R and aspirin; and (5) I\\/R and iloprost, a prostacyclin (PGI(2)) analogue. Lung injury was assessed by wet\\/dry ratio, myeloperoxidase (MPO) activity, and bronchoalveolar lavage (BAL) neutrophil counts. BAL levels of thromboxane, PGE(2), 6-keto-PGF(1)alpha (a hydrolysis product of prostacyclin), lipoxin A(4), and 15-epi-lipoxin A(4) were analyzed by enzyme immunoassay (EIA). Immunostaining for COX-2 was performed. RESULTS: I\\/R significantly increased tissue MPO, the wet\\/dry lung ratio, and neutrophil counts. These measures were significantly further aggravated by SC236 and improved by iloprost. I\\/R increased COX-2 immunostaining and both PGE(2) and 6-keto-PGF(1alpha) levels in BAL. SC236 markedly reduced these prostanoids and lipoxin A(4) compared with I\\/R alone. Iloprost markedly increased lipoxin A(4) levels. The deleterious effect of SC236 and the beneficial effect of iloprost was associated with a reduction and an increase, respectively, in lipoxin A(4) levels. CONCLUSIONS: Lipoxin A(4) warrants further evaluation as a mediator of COX-2 regulated lung protection.

  13. Anti-inflammatory effect of Euphorbia supina extract in dextran sulfate sodium-induced colitis mice.

    Science.gov (United States)

    Cha, Ji-Yun; Jeon, Yong-Deok; Xin, Mingjie; Kim, Do-Kuk; Lee, Hoon-Yeon; Kim, Bo-Ram; Hwang, Sung-Woo; Kim, Dae-Ki; Jin, Jong-Sik; Lee, Young-Mi

    2017-11-01

    The aim of this study is to examine the anti-inflammatory effect of Euphorbia supina (ES) ethanol extract in dextran sulfate sodium (DSS)-induced experimental colitis model. ES was per orally administered at different doses of 4 or 20 mg/kg body weight with 5% DSS in drinking water for 7 days. Twenty mg/kg of ES administration regulated body weight decrease, recovered colon length shortening, and increased disease activity index score and myeloperoxidase level in DSS-induced colitis. Histological features showed that 20 mg/kg of ES administration suppressed edema, mucosal damage, and the loss of crypts induced by DSS. Furthermore, ES suppressed the expressions of COX-2, iNOS, NF-kB, IkBα, pIkBα in colon tissue. These findings demonstrated a possible effect of amelioration of ulcerative colitis and could be clinically applied.

  14. Scientists Spot Genes Behind Crohn's, Ulcerative Colitis

    Science.gov (United States)

    ... medlineplus.gov/news/fullstory_166957.html Scientists Spot Genes Behind Crohn's, Ulcerative Colitis Large study finds key ... Researchers say they've come closer to pinpointing genes linked with inflammatory bowel diseases such as Crohn's ...

  15. Diagnosis and treatment of microscopic colitis.

    Science.gov (United States)

    Okamoto, Ryuichi; Negi, Mariko; Tomii, Syohei; Eishi, Yoshinobu; Watanabe, Mamoru

    2016-08-01

    Microscopic colitis (MC) designates two types of chronic diarrhea diseases, which are lymphocytic colitis and collagenous colitis. The prevalence of microscopic colitis is increasing in both Western and Eastern countries, possibly due to the high incidence of colonoscopic survey in chronic diarrhea patients. Although the overall prognosis of MC patients is mostly good, it should be noted that appropriate diagnosis and choice of treatment is required to assure a good clinical outcome for MC patients. Also, a certain population of MC patients may take a severe and refractory clinical course, and thus require advanced clinical care using medications supported by less evidence. In this review, we would like to feature the essential points regarding the diagnosis of MC, and also describe the current standard of treatments for MC patients. In addition, we would like to add some findings from the national survey and research carried out in Japan, to compare those data with the western countries.

  16. Acute Ischaemic Colitis- A Case Report

    Directory of Open Access Journals (Sweden)

    M Basra

    2012-03-01

    Full Text Available Acute ischaemic colitis (AIC is being increasingly recognised as an uncommon cause of abdominal pain associated with fresh bleeding per rectum. It is paramount to maintain a high index of suspicion and adopt appropriate management strategies to avoid complications and inappropriate interventions. In this paper, we describe a case of AIC and review literature pertinent to the management of this condition. Keywords: Ischaemic colitis, acute abdomen, management.

  17. The economics of adalimumab for ulcerative colitis.

    Science.gov (United States)

    Xie, Feng

    2015-06-01

    Ulcerative colitis is a chronic inflammatory disease, characterized by diffuse mucosal inflammation in the colon. Adalimumab, as a TNF-α blocker, offers a safe and efficacious treatment option for patients with moderate to severe ulcerative colitis and refractory or intolerant to conventional medications; however, its cost-effectiveness profile has not yet been well established. Future economic evaluations should choose appropriate comparators in the context of target-reimbursement decision making and focus on cost-effectiveness over a long time horizon.

  18. Case report: Pentoxifylline treatment in microscopic colitis.

    Science.gov (United States)

    Cotter, Thomas G; Kamboj, Amrit K; Hicks, Stephen Bradley; Tremaine, William J; Loftus, Edward V; Pardi, Darrell S

    2017-11-01

    Microscopic colitis is a common cause of diarrhea. Pentoxifylline, a xanthine derivative with anti-tumor necrosis factor-alpha properties, is prescribed for intermittent claudication and other disorders. Our goal was to evaluate the outcomes of patients with microscopic colitis treated with pentoxifylline. Nine patients with microscopic colitis (8 collagenous colitis and 1 lymphocytic colitis) seen at Mayo Clinic, Rochester, between January 1, 1997 and November 30, 2016, were included. The median age was 56.9 years (range 51.6-60.2), 8 were female (89%), and the median disease duration was 64.8 months (range 60-109). The indications for treatment were budesonide refractoriness in 7 patients, budesonide dependence in 1 patient, and budesonide intolerance in 1 patient. A histological diagnosis of microscopic colitis was confirmed in all patients. Pentoxifylline 400 mg three times a day was used for a median of 3 months (range 2.5-8.3). Complete response occurred in 1 patient (11%) and partial response in 3 patients (33%). The patient who achieved complete response was treated with pentoxifylline due to budesonide intolerance, and completed 43 months of successful maintenance therapy. There were no adverse effects reported. The majority of budesonide-experienced patients with active microscopic colitis did not respond to pentoxifylline. However, it was well-tolerated, with 1 patient achieving long-term remission and one-third of the cohort having a partial response. Larger controlled studies are required to evaluate the efficacy of pentoxifylline and predictors of response in microscopic colitis. In particular, patients who are not budesonide-refractory may be more likely to respond.

  19. Alkaline ceramidase 3 deficiency aggravates colitis and colitis-associated tumorigenesis in mice by hyperactivating the innate immune system

    Science.gov (United States)

    Wang, K; Xu, R; Snider, A J; Schrandt, J; Li, Y; Bialkowska, A B; Li, M; Zhou, J; Hannun, Y A; Obeid, L M; Yang, V W; Mao, C

    2016-01-01

    Increasing studies suggest that ceramides differing in acyl chain length and/or degree of unsaturation have distinct roles in mediating biological responses. However, still much remains unclear about regulation and role of distinct ceramide species in the immune response. Here, we demonstrate that alkaline ceramidase 3 (Acer3) mediates the immune response by regulating the levels of C18:1-ceramide in cells of the innate immune system and that Acer3 deficiency aggravates colitis in a murine model by augmenting the expression of pro-inflammatory cytokines in myeloid and colonic epithelial cells (CECs). According to the NCBI Gene Expression Omnibus (GEO) database, ACER3 is downregulated in immune cells in response to lipopolysaccharides (LPS), a potent inducer of the innate immune response. Consistent with these data, we demonstrated that LPS downregulated both Acer3 mRNA levels and its enzymatic activity while elevating C18:1-ceramide, a substrate of Acer3, in murine immune cells or CECs. Knocking out Acer3 enhanced the elevation of C18:1-ceramide and the expression of pro-inflammatory cytokines in immune cells and CECs in response to LPS challenge. Similar to Acer3 knockout, treatment with C18:1-ceramide, but not C18:0-ceramide, potentiated LPS-induced expression of pro-inflammatory cytokines in immune cells. In the mouse model of dextran sulfate sodium-induced colitis, Acer3 deficiency augmented colitis-associated elevation of colonic C18:1-ceramide and pro-inflammatory cytokines. Acer3 deficiency aggravated diarrhea, rectal bleeding, weight loss and mortality. Pathological analyses revealed that Acer3 deficiency augmented colonic shortening, immune cell infiltration, colonic epithelial damage and systemic inflammation. Acer3 deficiency also aggravated colonic dysplasia in a mouse model of colitis-associated colorectal cancer. Taken together, these results suggest that Acer3 has an important anti-inflammatory role by suppressing cellular or tissue C18:1-ceramide, a

  20. 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. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  1. Microscopic colitis: clinical and pathologic perspectives.

    Science.gov (United States)

    Münch, Andreas; Langner, Cord

    2015-02-01

    Microscopic colitis is a chronic inflammatory bowel disease characterized by chronic nonbloody diarrhea and specific histopathology features. Active disease, defined as 3 or more stools or 1 or more watery stools per day, significantly reduces quality of life. Epidemiologic studies have found the incidence and prevalence of microscopic colitis to be comparable with those of Crohn's disease and ulcerative colitis. Nevertheless, microscopic colitis is still under-recognized in clinical practice-most health care workers know little about its etiology and pathophysiology. Furthermore, there are many challenges to the diagnosis and treatment of patients. We review the epidemiologic and clinical features of this disorder and discuss its pathogenesis. We also outline the criteria for histopathologic evaluation of microscopic colitis, recently published by the European Consensus on Inflammatory Bowel Disease, and discuss a treatment algorithm created by the European Microscopic Colitis Group. Treatment options for patients with budesonide-refractory disease are discussed. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

  2. Activation of REG family proteins in colitis.

    Science.gov (United States)

    Granlund, Atle van Beelen; Beisvag, Vidar; Torp, Sverre H; Flatberg, Arnar; Kleveland, Per Martin; Ostvik, Ann Elisabeth; Waldum, Helge L; Sandvik, Arne K

    2011-11-01

    To do a genome-wide gene expression study of active and inactive ulcerative colitis and Crohn's disease (inflammatory bowel disease--IBD) and examine the most differentially expressed genes. As the study showed an extreme upregulation of all regenerating islet-derived genes (REG proteins) in active IBD, we further studied the expression of REGs on protein level in active and inactive IBD, as well as in non-IBD (pseudomembranous) colitis. Microarray analysis was done on a total of 100 pinch biopsy samples from healthy controls and patients with Crohn's disease or ulcerative colitis. Tissue samples from IBD and pseudomembranous colitis were examined with routine histology and immunohistochemical analysis for REGIα, REGIV, DEFA6, and serotonin. REG mRNAs were up to 83 times overexpressed in diseased mucosa compared with mucosa from healthy individuals. REGIα and REGIV were overexpressed at immunohistochemistry and located to different mucosal cell types. REGIα was expressed in basal half of crypts, REGIV in mid and outer parts of crypts and in surface epithelium and seems to be stored in, and secreted from, goblets. Pseudomembranous colitis samples showed similar staining patterns, and some IBD samples stained REG positive without inflammation on routine histology. All REG family mRNAs are upregulated in IBD. REGIα and REGIV have different cellular localization, possibly reflecting different biological functions. REG protein expression also in pseudomembranous colitis shows that REG family proteins are regulated in inflammatory injury and repair, not specifically for IBD as previously thought.

  3. Allergic colitis: a mimic of Hirschsprung disease

    Energy Technology Data Exchange (ETDEWEB)

    Bloom, D.A. [Department of Radiology, Children`s Radiological Institute, Columbus Children`s Hospital, OH (United States); Buonomo, C. [Department of Radiology, Children`s Hospital, Harvard Medical School, Boston, Massachusetts (United States); Fishman, S.J. [Department of Surgery, Children`s Hospital, Harvard Medical School, Boston, Massachusetts (United States); Furuta, G.; Nurko, S. [Department of Gastroenterology, Children`s Hospital, Harvard Medical School, Boston, Massachusetts (United States)

    1999-01-01

    Background. Allergy to cow milk protein is a common cause of gastrointestinal symptoms in infancy. Milk allergy is usually a clinical diagnosis, and thus there have been few reports of the radiographic findings. Objective. To describe the barium enema findings of allergic colitis and differentiate them from Hirschsprung disease. Materials and methods. Four infants (age range 7 days-5 weeks) with constipation underwent barium enema to exclude Hirschsprung disease. Radiographic findings were correlated with the pathologic specimens from suction rectal biopsy. Results. All enemas revealed irregular narrowing of the rectum and a transition zone. Rectal biopsies in each case demonstrated ganglion cells and evidence of an allergic colitis, with inflammatory infiltrates in the lamina propria. A diagnosis of milk allergy colitis was made and symptoms resolved after removal of milk from the diet. Conclusions. Milk allergy is common in infancy. The rectum is a primary target organ, with allergic colitis often diagnosed on clinical grounds alone. However, a child with allergic colitis may be referred to radiology for barium enema, especially if constipation is present. The radiologist should be aware of the unique imaging findings of allergic colitis, so as to avoid confusion with Hirschsprung disease and perhaps an unnecessary rectal biopsy. (orig.) With 4 figs., 1 tab., 17 refs.

  4. Microscopic Colitis and Medication Use

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    Monina F. Pascua

    2010-01-01

    Full Text Available Background The incidence of microscopic colitis (MC is increasing, but its etiology remains unknown. Case reports and limited controlled data suggest that commonly prescribed drugs may be triggers. The aim of this study was to evaluate the prevalence of selected medication use [Proton pump inhibitors (PPIs, HMG-CoA reductase inhibitors (statins, and Selective serotonin reuptake inhibitors (SSRIs] in patients with MC compared to ‘random controls’ and ‘diarrhea controls.' Methods All patients were selected from primary care practices of a university health system during 2002 to 2007. Patients with biopsy proven lymphocytic or collagenous colitis were identified as cases. Diarrhea controls consisted of a 10:1 random sample of patients with chronic diarrhea and normal colon biopsies. Ten random controls were matched to each case on sex and index date (date of biopsy proven diagnosis. Drugs prescribed within the year prior to the index date were collected from the electronic medical record system. Results 26 cases (median age 68.9 yrs, 259 random, and 259 diarrhea controls were identified. The adjusted ORs for PPI, SSRI, and statin prescription within 12 months of diagnosis of MC between cases and diarrhea controls were 0.28 (0.07-1.07, 0.87 (0.28-2.64, 1.12 (0.34-3.71 respectively. Use of PPI and statins was less common in MC patients than in random controls ( P < 0.05 for both comparisons. Conclusions While prior data suggest that PPIs, statins, and SSRIs may be etiologically related to MC, our study found no increased association with these drugs.

  5. Experimental pollinator decline affects plant reproduction and is mediated by plant mating system

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    Ørjan Totland

    2013-10-01

    Full Text Available There is growing concern that current pollinator decline will affect the reproduction of plant species, potentially driving a decline in plant population densities. We experimentally tested whether a reduction in flower visitation caused a reduction in fertilization rate in several species, and whether any reduction in fecundity of species depends on their degree of reproductive dependence on pollinators and their attractiveness for pollinators. We recorded visitation rate, fertilization rate, seed weight, flower size and density of nineteen insect-pollinated perennial herbs inside thirty 2 x 2 m dome-shaped cages covered with fishnet (experimental plots and in thirty control plots in a Norwegian hay meadow. We used a bagging experiment to estimate the ability of the study species to produce seeds in the absence of pollinators. The visitation rate for fifteen of nineteen study species was lower inside cages than outside and only three of the fifteen species showed significantly reduced fertilization rates in the experimental plots. The magnitude of reduction in fertilization rate was positively related to the degree of pollinator dependence, but not to their attractiveness for pollinators or to the reduction in visitation rate. Seed weight was not affected by the experiment. The lack of an overall effect of reduced pollinator visitation on fertilization rate suggests that some species may be robust to a pollinator decline that could increase pollen limitation on plant reproduction. Our results suggest that species with greater pollinator dependence are more vulnerable to pollinator loss. NOTE: Supporting information to this article may be found in the left menu.

  6. Pseudomembranous Collagenous Colitis: A Case of Not-so-Microscopic Colitis.

    Science.gov (United States)

    Grunwald, Douglas; Mehta, Manisha; Sheth, Sunil G

    2016-08-01

    We present a 72-year-old male who developed progressive, watery diarrhea despite anti-motility agents. On colonoscopy, the mucosa was inflamed and covered with an exudate. Stool studies for Clostridium difficile and Escherichia coli were negative. Biopsies revealed pseudomembranous collagenous colitis, a rare form of microscopic colitis. His symptoms improved dramatically with budesonide therapy.

  7. Pseudomembranous Collagenous Colitis: A Case of Not-so-Microscopic Colitis

    OpenAIRE

    Grunwald, Douglas; Mehta, Manisha; Sheth, Sunil G.

    2016-01-01

    We present a 72-year-old male who developed progressive, watery diarrhea despite anti-motility agents. On colonoscopy, the mucosa was inflamed and covered with an exudate. Stool studies for Clostridium difficile and Escherichia coli were negative. Biopsies revealed pseudomembranous collagenous colitis, a rare form of microscopic colitis. His symptoms improved dramatically with budesonide therapy.

  8. Dimethyl Fumarate Ameliorates Lewis Rat Experimental Autoimmune Neuritis and Mediates Axonal Protection

    Science.gov (United States)

    Pitarokoili, Kalliopi; Ambrosius, Björn; Meyer, Daniela; Schrewe, Lisa; Gold, Ralf

    2015-01-01

    Background Dimethyl fumarate is an immunomodulatory and neuroprotective drug, approved recently for the treatment of relapsing-remitting multiple sclerosis. In view of the limited therapeutic options for human acute and chronic polyneuritis, we used the animal model of experimental autoimmune neuritis in the Lewis rat to study the effects of dimethyl fumarate on autoimmune inflammation and neuroprotection in the peripheral nervous system. Methods and Findings Experimental autoimmune neuritis was induced by immunization with the neuritogenic peptide (amino acids 53–78) of P2 myelin protein. Preventive treatment with dimethyl fumarate given at 45 mg/kg twice daily by oral gavage significantly ameliorated clinical neuritis by reducing demyelination and axonal degeneration in the nerve conduction studies. Histology revealed a significantly lower degree of inflammatory infiltrates in the sciatic nerves. In addition, we detected a reduction of early signs of axonal degeneration through a reduction of amyloid precursor protein expressed in axons of the peripheral nerves. This reduction correlated with an increase of nuclear factor (erythroid derived 2)-related factor 2 positive axons, supporting the neuroprotective potential of dimethyl fumarate. Furthermore, nuclear factor (erythroid derived 2)-related factor 2 expression in Schwann cells was only rarely detected and there was no increase of Schwann cells death during EAN. Conclusions We conclude that immunmodulatory and neuroprotective dimethyl fumarate may represent an innovative therapeutic option in human autoimmune neuropathies. PMID:26618510

  9. Dimethyl Fumarate Ameliorates Lewis Rat Experimental Autoimmune Neuritis and Mediates Axonal Protection.

    Directory of Open Access Journals (Sweden)

    Kalliopi Pitarokoili

    Full Text Available Dimethyl fumarate is an immunomodulatory and neuroprotective drug, approved recently for the treatment of relapsing-remitting multiple sclerosis. In view of the limited therapeutic options for human acute and chronic polyneuritis, we used the animal model of experimental autoimmune neuritis in the Lewis rat to study the effects of dimethyl fumarate on autoimmune inflammation and neuroprotection in the peripheral nervous system.Experimental autoimmune neuritis was induced by immunization with the neuritogenic peptide (amino acids 53-78 of P2 myelin protein. Preventive treatment with dimethyl fumarate given at 45 mg/kg twice daily by oral gavage significantly ameliorated clinical neuritis by reducing demyelination and axonal degeneration in the nerve conduction studies. Histology revealed a significantly lower degree of inflammatory infiltrates in the sciatic nerves. In addition, we detected a reduction of early signs of axonal degeneration through a reduction of amyloid precursor protein expressed in axons of the peripheral nerves. This reduction correlated with an increase of nuclear factor (erythroid derived 2-related factor 2 positive axons, supporting the neuroprotective potential of dimethyl fumarate. Furthermore, nuclear factor (erythroid derived 2-related factor 2 expression in Schwann cells was only rarely detected and there was no increase of Schwann cells death during EAN.We conclude that immunomodulatory and neuroprotective dimethyl fumarate may represent an innovative therapeutic option in human autoimmune neuropathies.

  10. Development of a Loop-Mediated Isothermal Amplification Assay for Rapid Detection of Trichosporon asahii in Experimental and Clinical Samples

    Science.gov (United States)

    Zhou, Jianfeng; Liao, Yong; Li, Haitao; Lu, Xuelian; Han, Xiufeng; Tian, Yanli; Chen, Shanshan; Yang, Rongya

    2015-01-01

    Invasive trichosporonosis is a deep mycosis found mainly in immunocompromised hosts, and the major pathogen is Trichosporon asahii. We detected the species-specific intergenic spacers (IGS) of rRNA gene of T. asahii using a loop-mediated isothermal amplification (LAMP) assay in 15 isolates with 3 different visualization methods, including SYBR green detection, gel electrophoresis, and turbidimetric methods. The LAMP assay displayed superior rapidity to other traditional methods in the detection time; that is, only 1 h was needed for detection and identification of the pathogen DNA. Furthermore, the detection limit of the LAMP assay was more sensitive than the PCR assay. We also successfully detect the presence of T. asahii in samples from experimentally infected mice and samples from patients with invasive trichosporonosis caused by T. asahii, suggesting that this method may become useful in clinical applications in the near future. PMID:25692144

  11. Local administration of Tiludronic Acid downregulates important mediators involved in periodontal tissue destruction in experimental periodontitis in rats.

    Science.gov (United States)

    Furlaneto, Flávia A C; Nunes, Nara L T; Souza, Ricardo B; Yamamoto, Kely O; Oliveira Filho, Ivan Lima; Frota, Nicolly P R; Chaves, Hellíada; Lisboa, Mario; Taba, Mario; Ervolino, Edilson; Messora, Michel R

    2018-04-01

    The purpose of this study was to evaluate whether local administration of TIL could influence the expression of the inflammatory mediators IL-1β, TNF-α, MMP-8 and COX-2 in rats with experimental periodontitis (EP). Twenty-four adult male rats (Rattus norvegicus, albinus, Wistar) were assigned to groups C, EP, EP-TIL (CControl group, EP-Periodontitis groups). On EP groups, a ligature was placed around maxillary 2nd molars on day 1. On group EP-TIL, 20 μL of TIL solution (1 mg/kg body weight) was injected into the subperiosteal palatal area adjacent to the maxillary 2nd molar every other day until euthanasia (day 11). Alveolar bone loss was morphometrically analyzed. mRNA expressions of IL-1β, TNF-α, MMP-8 and COX-2 were assessed by qPCR. IL-1β, TNF-α, MMP-8 and COX-2 were immunohistochemically analyzed. Data were analyzed statistically. Group EP-TIL presented reduced alveolar bone loss when compared with group EP (p  0.05). Within the limits of this study, it can be concluded that local administration of TIL downregulates important mediators involved in periodontal tissue destruction in ligature-induced periodontitis in rats. Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. Experimental reduction of pain catastrophizing modulates pain report but not spinal nociception as verified by mediation analyses.

    Science.gov (United States)

    Terry, Ellen L; Thompson, Kathryn A; Rhudy, Jamie L

    2015-08-01

    Pain catastrophizing is associated with enhanced pain; however, the mechanisms by which it modulates pain are poorly understood. Evidence suggests that catastrophizing modulates supraspinal processing of pain but does not modulate spinal nociception (as assessed by nociceptive flexion reflex [NFR]). Unfortunately, most NFR studies have been correlational. To address this, this study experimentally reduced catastrophizing to determine whether it modulates spinal nociception (NFR). Healthy pain-free participants (N = 113) were randomly assigned to a brief 30-minute catastrophizing reduction manipulation or a control group that received pain education. Before and after manipulations, 2 types of painful stimuli were delivered to elicit (1) NFR (single trains of stimuli) and (2) temporal summation of NFR (3 stimulations at 2 Hz). After each set of stimuli, participants were asked to report their pain intensity and unpleasantness, as well as their situation-specific catastrophizing. Manipulation checks verified that catastrophizing was effectively reduced. Furthermore, pain intensity and unpleasantness to both stimulation types were reduced by the catastrophizing manipulation, effects that were mediated by catastrophizing. Although NFRs were not affected by the catastrophizing manipulation, temporal summation of NFR was reduced. However, this effect was not mediated by catastrophizing. These results indicate that reductions in catastrophizing lead to reductions in pain perception but do not modulate spinal nociception and provides further evidence that catastrophizing modulates pain at the supraspinal, not the spinal, level.

  13. Emu Oil Improves Clinical Indicators of Disease in a Mouse Model of Colitis-Associated Colorectal Cancer.

    Science.gov (United States)

    Chartier, Lauren C; Howarth, Gordon S; Lawrance, Ian C; Trinder, Debbie; Barker, Scott J; Mashtoub, Suzanne

    2017-12-06

    Ulcerative colitis is a remitting and relapsing inflammatory bowel disorder. Current treatments are limited, and if poorly controlled, colitis may progress to colorectal cancer. Previously, Emu Oil protected the intestine in experimental models of gut damage. We aimed to determine whether Emu Oil could reduce the severity of chronic colitis and prevent the onset of neoplasia in a mouse model of colitis-associated colorectal cancer. Female C57BL/6 mice were injected (day 0) with azoxymethane, followed by ad libitum access to three dextran sulfate sodium/water cycles (7 days of dextran sulfate sodium and 14 days of water). Mice (n = 9/group) were orally administered either water or Emu Oil (low dose 80 µL or high dose 160 µL), thrice weekly for 9 weeks. Bodyweight and disease activity index were measured daily. Colitis progression was monitored by colonoscopy on days 20, 41 and 62. At killing, tumor number and size were recorded. Azoxymethane/dextran sulfate sodium induced significant bodyweight loss (maximum 24%) which was attenuated by Emu Oil treatment (low dose days 9, 10, 14: maximum 7%; high dose days 7-15, 30-36: maximum 11%; p Oil reduced disease activity index of azoxymethane/dextran sulfate sodium mice at most time points (maximum 20%; p Oil reduced colonoscopically assessed colitis severity (days 20 and 62) compared to disease controls (p Oil resulted in fewer small colonic tumors (p Oil improved clinical indicators and reduced severity of colitis-associated colorectal cancer, suggesting therapeutic potential in colitis management.

  14. Protective effect of sanguinarine against acetic acid-induced ulcerative colitis in mice.

    Science.gov (United States)

    Niu, Xiaofeng; Fan, Ting; Li, Weifeng; Huang, Huimin; Zhang, Yanmin; Xing, Wei

    2013-03-15

    The quaternary ammonium salt, sanguinarine (SANG), is of great practical and research interest because of its pronounced, widespread physiological effects, which promote anti-microbial and anti-inflammatory responses in experimental animals. Although SANG is originally shown to possess anti-inflammatory properties and it has been used to treat various inflammatory diseases, its effects on ulcerative colitis have not been previously explored. The aim of the present study is to evaluate the effect of SANG on acetic acid-induced ulcerative colitis in mice. Experimental animals received SANG (1, 5 and 10 mg/kg, p.o.) and sulfasalazine (500 mg/kg, p.o.) for seven consecutive days after induction of colitis by intra-rectal acetic acid (5% v/v) administration. The colonic mucosal injury was assessed by clinical, macroscopic, biochemical and histopathological examinations. SANG treatment significantly decreased mortality rate, body weight loss, disease activity index (DAI), wet colon weight, macroscopic and histological score when compared to acetic acid-induced controls. In addition, administration of SANG effectively inhibited p65 NF-κB protein expression and MPO activity accumulation. The levels of TNF-α and IL-6 in the serum and colon tissue of mice with experimental colitis were decreased by SANG in a concentration-dependent manner in response to p65 NF-κB. The possible mechanism of protection on experimental colitis was that SANG could be through attenuating early steps of inflammation as well as decreasing the expression of NF-κB and subsequent pro-inflammatory cytokines production. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Lycopene abrogates Aβ(1-42)-mediated neuroinflammatory cascade in an experimental model of Alzheimer's disease.

    Science.gov (United States)

    Sachdeva, Anand Kamal; Chopra, Kanwaljit

    2015-07-01

    Neuroinflammation characterized by glial activation and release of proinflammatory mediators is considered to play a critical role in the pathogenesis of Alzheimer's disease (AD). β-Amyloid1-42 (Aβ1-42)-induced learning and memory impairment in rats is believed to be associated with neuronal inflammation. The present study was designed to investigate the effect of lycopene, a potent antioxidant and anti-inflammatory carotenoid, in intracerebroventricular (i.c.v.) Aβ1-42-induced neuroinflammatory cascade along with learning and memory impairment in rats. I.c.v. Aβ1-42 was injected bilaterally followed by treatment with lycopene or rivastigmine for 14 days. Morris water maze and elevated plus maze tests were used to assess the memory function. Rats were sacrificed and brains harvested to evaluate various biochemical parameters and mitochondrial complex activities in postmitochondrial supernatant fractions of cerebral cortex and hippocampus of rat brains. The levels of tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), tumor growth factor β (TGF-β), nuclear factor-κB (NF-κB) and caspase-3 were assessed by enzyme-linked immunosorbent assay analysis. Lycopene remediated Aβ-induced learning and memory deficits in a dose-dependent manner. Aβ1-42-induced mitochondrial dysfunction along with surge of proinflammatory cytokines TNF-α, TGF-β and IL-1β as well as NF-κB and caspase-3 activity in rat brain was significantly reduced with lycopene treatment. The amelioration of Aβ1-42-induced spatial learning and memory impairment by lycopene could be linked, at least in part, to the inhibition of NF-κB activity and the down-regulation of expression of neuroinflammatory cytokines, suggesting that lycopene may be a potential candidate for AD treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Edge-mediated patterns of seed removal in experimentally connected and fragmented landscapes.

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    Craig, Michael, T.; Orrock, John, L.; Brudvig, Lars, A.

    2011-09-07

    While biological reserves remain central to biodiversity conservation, the amount of area available for terrestrial reserves may be inadequate for many taxa. Biodiversity spillover - the promotion of diversity in matrix areas surrounding reserves - might help address this shortfall in reserve area. However, the mechanistic underpinning of spillover remains uninvestigated. Two fundamental processes - seed dispersal and establishment - might generate plant biodiversity spillover. Here, we investigate the role of establishment in promoting spillover by assessing post-dispersal seed predation, a key component of establishment, in the matrix of a replicated, large-scale habitat fragmentation experiment, where spillover is relevated around patches connected by landscape corridors. Our results show that matrix seed predation may constrain the distance of this spillover effect by reducing establishment: seed removal was least at the matrix edge and increased further into the matrix. We found some support for matrix seed predation underpinning previously reported landscape-level variation in spillover. Of the three species we investigated, two showed evidence for elevated seed predation in the matrix surrounding the unconnected patches around which the lowest levels of spillover occur. However, seed predation did not explain connectivity-enhanced spillover, suggesting that seed dispersal likely drives this pattern. Management activities that increase seed deposition in the matrix may have beneficial effects via spillover. Our work also illustrates that matrix-mediated gradients in seed predation may be widespread, but likely vary depending upon matrix composition and the ecological system under consideration. In fragmented landscapes, this gradient could impact the distribution, abundance, and spread of plant species.

  17. Mindfulness May Be Helpful for People with Ulcerative Colitis

    Science.gov (United States)

    ... Mindfulness May Be Helpful for People With Ulcerative Colitis Share: © Jupiter Images Mindfulness-based stress reduction (MBSR), ... and decrease perceived stress in people with ulcerative colitis. These findings come from a small pilot study ...

  18. 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...

  19. 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....

  20. Processed coffee alleviates DSS-induced colitis in mice

    Directory of Open Access Journals (Sweden)

    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

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

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    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.

  2. Vaccine-mediated immune responses to experimental pulmonary Cryptococcus gattii infection in mice.

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    Ashok K Chaturvedi

    Full Text Available Cryptococcus gattii is a fungal pathogen that can cause life-threatening respiratory and disseminated infections in immune-competent and immune-suppressed individuals. Currently, there are no standardized vaccines against cryptococcosis in humans, underlying an urgent need for effective therapies and/or vaccines. In this study, we evaluated the efficacy of intranasal immunization with C. gattii cell wall associated (CW and/or cytoplasmic (CP protein preparations to induce protection against experimental pulmonary C. gattii infection in mice. BALB/c mice immunized with C. gattii CW and/or CP protein preparations exhibited a significant reduction in pulmonary fungal burden and prolonged survival following pulmonary challenge with C. gattii. Protection was associated with significantly increased pro-inflammatory and Th1-type cytokine recall responses, in vitro and increased C. gattii-specific antibody production in immunized mice challenged with C. gattii. A number of immunodominant proteins were identified following immunoblot analysis of C. gattii CW and CP protein preparations using sera from immunized mice. Immunization with a combined CW and CP protein preparation resulted in an early increase in pulmonary T cell infiltrates following challenge with C. gattii. Overall, our studies show that C. gattii CW and CP protein preparations contain antigens that may be included in a subunit vaccine to induce prolonged protection against pulmonary C. gattii infection.

  3. Primary sclerosing cholangitis and Biliary cirrhosis associated with Ulcerative colitis

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    Aleem Ahmed Khan

    2011-07-01

    Full Text Available Primary sclerosing cholangitis and Ulcerative colitis are caused by progressive inflammation of the bile duct and large intestine respectively. The existence of any plausible association between Primary sclerosing cholangitis and Ulcerative colitis remains highly elusive. Little is known about the incidence and prevalence of primary sclerosing cholangitis with concomitant Ulcerative colitis in the Indian subcontinent. We report a case of Primary sclerosing cholangitis with long standing Ulcerative colitis which later also developed Primary biliary cirrhosis.

  4. A model-specific role of microRNA-223 as a mediator of kidney injury during experimental sepsis.

    Science.gov (United States)

    Colbert, James F; Ford, Joshay A; Haeger, Sarah M; Yang, Yimu; Dailey, Kyrie L; Allison, Kristen C; Neudecker, Viola; Evans, Christopher M; Richardson, Vanessa L; Brodsky, Kelley S; Faubel, Sarah; Eltzschig, Holger K; Schmidt, Eric P; Ginde, Adit A

    2017-08-01

    Sepsis outcomes are heavily dependent on the development of septic organ injury, but no interventions exist to interrupt or reverse this process. microRNA-223 (miR-223) is known to be involved in both inflammatory gene regulation and host-pathogen interactions key to the pathogenesis of sepsis. The goal of this study was to determine the role of miR-223 as a mediator of septic kidney injury. Using miR-223 knockout mice and multiple models of experimental sepsis, we found that miR-223 differentially influences acute kidney injury (AKI) based on the model used. In the absence of miR-223, mice demonstrated exaggerated AKI in sterile models of sepsis (LPS injection) and attenuated AKI in a live-infection model of sepsis (cecal ligation and puncture). We demonstrated that miR-223 expression is induced in kidney homogenate after cecal ligation and puncture, but not after LPS or fecal slurry injection. We investigated additional potential mechanistic explanations including differences in peritoneal bacterial clearance and host stool virulence. Our findings highlight the complex role of miR-223 in the pathogenesis of septic kidney injury, as well as the importance of differences in experimental sepsis models and their consequent translational applicability. Copyright © 2017 the American Physiological Society.

  5. Alleviation of antioxidant defense system by ozonized olive oil in DNBS-induced colitis in rats.

    Science.gov (United States)

    Abu-Gharbieh, Eman; Bayoumi, Fatehia A; Ahmed, Naglaa G

    2014-01-01

    The aim of the study was to evaluate the potential protective effect of ozonized olive oil (OZO) in 2,4-dinitrobenzene sulphuric acid (DNBS) induced colitis in rats and to elucidate the role of some antioxidant defense system (superoxide dismutase "SOD," glutathione peroxidase "GSH-Px," and catalase "CAT") in these effects. The physicochemical parameters including viscosity, peroxide, and acid values of olive oil and OZO were evaluated. The animals were divided into several groups and the colitis was induced in the rats by intracolonic instillation of DNBS at dose of 15 mg/rat. Olive oil (OO) at dose of 6 mg/kg and OZO at doses of 3 and 6 mg/kg was administered orally for 7 days, starting the day before induction of colitis. Our results showed that macroscopic and microscopic damage scores were significantly reduced in a dose response manner in rats pretreated with OZO only. In contrast, CAT, GSH-Px, and SOD activities were significantly increased in the distal colon of inflamed animals pretreated with OZO with respect to control group dose dependently. Results demonstrate that OZO pretreatment exerts protective effects in DNBS induced colitis in rats and provide evidence that the protective effects of OZO are mediated by stimulation of some antioxidant enzymes.

  6. Alleviation of Antioxidant Defense System by Ozonized Olive Oil in DNBS-Induced Colitis in Rats

    Directory of Open Access Journals (Sweden)

    Eman Abu-Gharbieh

    2014-01-01

    Full Text Available The aim of the study was to evaluate the potential protective effect of ozonized olive oil (OZO in 2,4-dinitrobenzene sulphuric acid (DNBS induced colitis in rats and to elucidate the role of some antioxidant defense system (superoxide dismutase “SOD,” glutathione peroxidase “GSH-Px,” and catalase “CAT” in these effects. The physicochemical parameters including viscosity, peroxide, and acid values of olive oil and OZO were evaluated. The animals were divided into several groups and the colitis was induced in the rats by intracolonic instillation of DNBS at dose of 15 mg/rat. Olive oil (OO at dose of 6 mg/kg and OZO at doses of 3 and 6 mg/kg was administered orally for 7 days, starting the day before induction of colitis. Our results showed that macroscopic and microscopic damage scores were significantly reduced in a dose response manner in rats pretreated with OZO only. In contrast, CAT, GSH-Px, and SOD activities were significantly increased in the distal colon of inflamed animals pretreated with OZO with respect to control group dose dependently. Results demonstrate that OZO pretreatment exerts protective effects in DNBS induced colitis in rats and provide evidence that the protective effects of OZO are mediated by stimulation of some antioxidant enzymes.

  7. 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.

  8. Changing patterns of acute phase proteins and inflammatory mediators in experimental caprine coccidiosis.

    Science.gov (United States)

    Hashemnia, Mohammad; Khodakaram-Tafti, Azizollah; Razavi, Seyed Mostafa; Nazifi, Saeed

    2011-09-01

    This experiment was conducted to assess the changing patterns and relative values of acute phase proteins and inflammatory cytokines in experimental caprine coccidiosis. Eighteen newborn kids were allocated to 3 equal groups. Two groups, A and B, were inoculated with a single dose of 1×10(3) and1×10(5) sporulated oocysts of Eimeria arloingi, respectively. The third group, C, received distilled water as the control. Blood samples were collected from the jugular vein of each kid in both groups before inoculation and at days 7, 14, 21, 28, 35, and 42 post-inoculation (PI), and the levels of haptoglobin (Hp), serum amyloid A (SAA), TNF-α, and IFN-γ were measured. For histopathological examinations, 2 kids were selected from each group, euthanized, and necropsied on day 42 PI. Mean Hp concentrations in groups A and B (0.34 and 0.68 g/L) at day 7 PI were 3.2 and 6.3 times higher than the levels before inoculation. The mean SAA concentrations in groups A and B (25.6 and 83.5 µg/ml) at day 7 PI were 4.2 and 13.7 times higher than the levels before inoculation. The magnitude and duration of the Hp and SAA responses correlated well with the inoculation doses and the severity of the clinical signs and diarrhea in kids. These results were consistent with the histopathological features, which showed advanced widespread lesions in group B. In both groups, significant correlations were observed for TNF-α and IFN-γ with SAA and Hp, respectively. In conclusion, Hp and SAA can be useful non-specific diagnostic indicators in caprine coccidiosis.

  9. Changes in Synovial Fluid Inflammatory Mediators and Cartilage Biomarkers After Experimental Acute Equine Synovitis

    Directory of Open Access Journals (Sweden)

    Wang Guanying

    2015-04-01

    Full Text Available The purpose of the study was to define transient changes in the concentration of inflammatory biomarkers and cartilage biomarkers in the synovial fluid of joints following experimentally induced acute equine synovitis. Acute synovitis was induced in eight skeletally mature mares by a sterile intra-articular injection of 1 mL of phosphate-buffered saline (PBS containing 0.5 ng of lipopolysaccharide (LPS. The solution was injected into the right middle carpal joint. One mL of sterile PBS was injected into the left control joint. Synovial fluid was obtained at the baseline level and at 8, 24, and 168 h after injection. The levels of inflammatory biomarkers-prostaglandin E2 (PGE2, interleukin 1β (IL-1β, and tumour necrosis factor-α (TNF-α, and cartilage turnover biomarkers-collagenase-cleavage neoepitope of type II collagen (C2C and C-terminal crosslinked telopeptide type II collagen (CTX-II were detected with proper assays. Single injections of LPS raised the number of synovial white blood cells and concentrations of total protein, PGE2, IL-1β, TNF-α, C2C, and CTX-II. PGE2 and IL-1β rose sharply at 8 h, while TNF-α increased steadily through 8 h and 24 h, at that point; these three factors returned to the baseline level by 168 h. The time course of C2C and CTX-II concentrations peaked sharply at 24 h, and continued to be significantly elevated over the baseline level even at 168 h. Injections of LPS into the joints led to a temporal inflammatory response, which in turn increased local release of inflammatory biomarkers and significantly altered the concentrations of cartilage markers in the synovial fluid.

  10. Epithelial-specific Toll-like Receptor (TLR)5 Activation Mediates Barrier Dysfunction in Experimental Ileitis.

    Science.gov (United States)

    Lopetuso, Loris R; Jia, Ruo; Wang, Xiao-Ming; Jia, Li-Guo; Petito, Valentina; Goodman, Wendy A; Meddings, Jon B; Cominelli, Fabio; Reuter, Brian K; Pizarro, Theresa T

    2017-03-01

    A large body of evidence supports a central role of TLR5 and its natural ligand, flagellin, in Crohn's disease (CD), with the precise mechanism(s) still unresolved. We investigated the role of flagellin/TLR5 in SAMP1/YitFc (SAMP) mice, a spontaneous model of Crohn's disease-like ileitis. Ileal Tlr5 and serum antiflagellin IgG antibodies were increased in SAMP before the onset of inflammation and during established disease; these trends were abrogated in the absence of colonizing commensal bacteria. Irradiated SAMP receiving either wild-type (AKR) or SAMP bone marrow (BM) developed severe ileitis and displayed increased ileal Tlr5 compared with AKR recipients of either SAMP or AKR bone marrow, neither of which conferred ileitis, suggesting that elevated TLR5 in native SAMP is derived primarily from a nonhematopoietic (e.g., epithelial) source. Indeed, ileal epithelial TLR5 in preinflamed SAMP was increased compared with age-matched AKR and germ-free SAMP. TLR5-specific ex vivo activation of SAMP ileal tissues decreased epithelial barrier resistance, indicative of increased permeability, and was accompanied by altered expression of the tight junction proteins, claudin-3, occludin, and zonula occludens-1. Our results provide evidence that aberrant, elevated TLR5 expression is present in the ileal epithelium of SAMP mice, is augmented in the presence of the gut microbiome, and that TLR5 activation in response to bacterial flagellin results in a deficiency to maintain appropriate epithelial barrier integrity. Together, these findings represent a potential mechanistic pathway leading to the exacerbation and perpetuation of chronic gut inflammation in experimental ileitis and possibly, in patients with Crohn's disease.

  11. 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.

  12. Microscopic colitis: A review of etiology, treatment and refractory disease.

    Science.gov (United States)

    Park, Tina; Cave, David; Marshall, Christopher

    2015-08-07

    Microscopic colitis is a common cause of chronic, nonbloody diarrhea. Microscopic colitis is more common in women than men and usually affects patients in their sixth and seventh decade. This article reviews the etiology and medical management of microscopic colitis. The etiology of microscopic colitis is unknown, but it is associated with autoimmune disorders, such as celiac disease, polyarthritis, and thyroid disorders. Smoking has been identified as a risk factor of microscopic colitis. Exposure to medications, such as non-steroidal anti-inflammatory drugs, proton pump inhibitors, and selective serotonin reuptake inhibitors, is suspected to play a role in microscopic colitis, although their direct causal relationship has not been proven. Multiple medications, including corticosteroids, anti-diarrheals, cholestyramine, bismuth, 5-aminosalicylates, and immunomodulators, have been used to treat microscopic colitis with variable response rates. Budesonide is effective in inducing and maintaining clinical remission but relapse rate is as high as 82% when budesonide is discontinued. There is limited data on management of steroid-dependent microscopic colitis or refractory microscopic colitis. Immunomodulators seem to have low response rate 0%-56% for patients with refractory microscopic colitis. Response rate 66%-100% was observed for use of anti-tumor necrosis factor (TNF) therapy for refractory microscopic colitis. Anti-TNF and diverting ileostomy may be an option in severe or refractory microscopic colitis.

  13. Cytokine expression of microscopic colitis including interleukin-17.

    Science.gov (United States)

    Park, Eun-Kyoung; Park, Young Sook; Park, Dae Rim; Jung, Sung Ae; Han, Dong Soo; Jang, Byung Ik; Kim, Young Ho; Kim, Won Ho; Jo, Yun Ju; Lee, Ki Ho; Lee, Won Mi; Kim, Eun Kyung; Koo, Hae Soo

    2015-05-23

    Microscopic colitis is characterized by chronic watery diarrhea with specific pathological changes that can be diagnosed by microscopic examination. We performed immunohistochemical analysis of proinflammatory cytokines to investigate the pathogenic mechanism of microscopic colitis. This study consisted of six patients with lymphocytic colitis, six patients with collagenous colitis, and six patients with functional diarrhea but normal pathology. We performed an immunohistochemical analysis of the colonic mucosal biopsies to assess the expression of cyclo-oxygenase-2, interleukin-17, nuclear factor-κB, interferon-γ, inducible nitric oxide synthase, and tumor necrosis factor-α. We compared the quantity score of immunohistochemical staining among the groups. The microscopic colitis group showed significantly higher expression of cyclo-oxygenase-2, interleukin-17, nuclear factor-κB, and interferon-γ compared with the control group. Cytokine expression was similar between collagenous colitis and lymphocytic colitis. However, the expression of cyclo-oxygenase-2 was higher in collagenous colitis. Proinflammatory cytokines, including interleukin-17 and interferon-γ, are highly expressed in microscopic colitis. The expression of cyclo-oxygenase-2 was higher in collagenous colitis than in lymphocytic colitis. This study is the first on interleukin-17 expression in microscopic colitis patients.

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

    DEFF Research Database (Denmark)

    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....

  15. Oroxylin A inhibits colitis by inactivating NLRP3 inflammasome.

    Science.gov (United States)

    Zhou, Wei; Liu, Xiuting; Zhang, Xin; Tang, Jingjing; Li, Zhiyu; Wang, Qing; Hu, Rong

    2017-08-29

    NLRP3 inflammasome is a novel therapeutic target for inflammatory bowel disease (IBD). The aim of this study was to investigate the anti-inflammatory effect of a bioactive flavonoid-oroxylin A on the treatment of dextran sulfate sodium (DSS)-induced murine colitis via targeting NLRP3 inflammasome. In this study, we found that oroxylin A attenuated experimental colitis in mice, including loss of body weights, shortening of the colon lengths and infiltration of inflammatory cells. The production of IL-1β, IL-6 and TNF-α in colon was also markedly reduced by oroxylin A. Moreover, oroxylin A significantly decreased the expression of NLRP3 in intestinal mucosal tissue. In addition, NLRP3-/- mice were observably protected from DSS-induced acute colitis, and oroxylin A treatment had no effects on attenuating inflammation in NLRP3-/- mice. Further study found that the activation of NLRP3 inflammasome was dose-dependently inhibited by oroxylin A in both THP-Ms and BMDMs, followed by decrease in the cleavage of caspase-1 and secretion of IL-1β. This inhibitory effect of oroxylin A was due to restraint of the NLRP3 protein expression and the inflammasome formation in macrophages. Furthermore, the reduction of NLRP3 protein expression by oroxylin A was dependent on the inhibition of NF-κB p65 expression and nuclear translocation. Besides, oroxylin A directly suppressed the ASC speck formation and the inflammasome assembly which in turn restrained the activation of NLRP3 inflammasome. Our findings demonstrated that oroxylin A inhibited NLRP3 inflammasome activation and could potentially be used for the treatment of IBD.

  16. Immunosuppressive and biologic therapy for ulcerative colitis.

    Science.gov (United States)

    Ardizzone, Sandro; Cassinotti, Andrea; de Franchis, Roberto

    2012-12-01

    Recent insight into the pathogenesis of ulcerative colitis have led to the development of new treatment options. A better understanding of IBD pathophysiology has progressively led to a more frequent use of immunosuppressants and biologics. The use of the conventional immunomodulators, such as azathioprine, 6-mercaptopurine, methotrexate, cyclosporine and tacrolimus, and anti-TNF-α agents, such as infliximab and adalimumab, in the treatment of ulcerative colitis are reviewed. Moreover, the ongoing studies evaluating the efficacy of emerging immunosuppressants in treating patients with ulcerative colitis are discussed. An effort is made to explore some critical areas in which early and more diffuse use of these agents may be advocated. Ulcerative colitis is a chronic condition mainly affecting young people in their more productive age, and determining high indirect costs to the patient and to society. Thus, there is a need for optimizing and renewing our traditional therapeutic approach to UC, and new therapies beyond conventional treatment options possibly aiming to change the poor clinical course of many patients with ulcerative colitis. Keeping in mind this potentially new therapeutic scenario, there are some critical areas in which early and more diffuse use of conventional and emerging new immunomodulators is advocated.

  17. Interactive effects of ethanol on ulcerative colitis and its associated testicular dysfunction in pubertal BALB/c mice.

    Science.gov (United States)

    Adedara, Isaac A; Ajayi, Babajide O; Awogbindin, Ifeoluwa O; Farombi, Ebenezer O

    2017-11-01

    Available epidemiological reports have indicated an increase in the incidence of ulcerative colitis, as well as alcohol consumption, globally. The present study investigated the possible interactive effects of ethanol consumption on ulcerative colitis and its associated testicular dysfunction using six groups of 12 pubertal mice each. Group I (Control) mice received drinking water alone. Group II mice received ethanol alone at 5 g/kg body weight. Group III mice received 2.5% dextran sulphate sodium (DSS) in drinking water followed by normal drinking water. Groups IV, V, and VI mice received DSS followed by ethanol at 1.25, 2.5, and 5 g/kg, respectively. Administration of ethanol to mice with ulcerative colitis intensified the disease-activity index with marked reduction in colon length, colon mass index, body weight gain, and organo-somatic indices of testes and epididymis when compared with the DSS-alone group. Moreover, ethanol exacerbated colitis-mediated decrease in enzymatic and non-enzymatic antioxidants but increased the oxidative stress and inflammatory biomarkers in the testes and epididymis. The diminution in luteinizing hormone, follicle stimulating hormone, and testosterone levels was intensified following administration of ethanol to mice with ulcerative colitis that were administered 5 g/kg ethanol alone. The decrease in sperm functional parameters and testicular spermatogenic indices as well as histopathological damage in colon, testes, and epididymis was aggravated following administration of ethanol to mice with ulcerative colitis. In conclusion, the exacerbating effects of ethanol on ulcerative colitis-induced testicular dysfunction are related to increased oxidative stress and inflammation in the treated mice. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Oral caffeine administration ameliorates acute colitis by suppressing chitinase 3-like 1 expression in intestinal epithelial cells.

    Science.gov (United States)

    Lee, In-Ah; Low, Daren; Kamba, Alan; Llado, Victoria; Mizoguchi, Emiko

    2014-08-01

    The initial trigger of inflammatory bowel disease (IBD) can be partly attributed towards the interaction and invasion of intestinal epithelial cells (IECs) and submucosal compartments. Identifying safe and economical methods to block these interactions may help prevent the onset of early colitis. Chitinase 3-like 1 (CHI3L1) is an inducible host protein that facilitates bacterial attachment and invasion on/into IECs. Therefore, we test the hypothesis of inhibiting CHI3L1 using the pan-chitinase inhibitor caffeine to reduce the likelihood of early colitis onset. IEC lines were treated with caffeine (2.5 or 5 mM) and analyzed for CHI3L1 expression and the impact on bacterial invasion. In vivo, mice were treated with 2.5 mM caffeine and induced with 3.5 % dextran sulfate sodium (DSS)-mediated colitis and subsequently analyzed colitis development. In vitro, caffeine treatment in IEC lines down-regulated CHI3L1 mRNA expression, which resulted in the reduction of bacterial invasion in a caffeine dose-dependent manner. In vivo, mice treated with caffeine displayed a delayed response towards DSS-induced colitis, characterized by lower body weight loss, clinical and histological scores. Bacterial translocation into other organs and pro-inflammatory cytokines production were also reduced in the caffeine-treated mice with DSS-induced colitis. Caffeine treatment also resulted in the loss of CHI3L1-associated AKT signaling pathway activation both in vitro and in vivo. Development of acute colitis is reduced upon caffeine treatment. The mechanism involves the down-regulation of CHI3L1 expression and its associated bacterial interaction effect. Therefore, caffeine is proposed as a safe and economical candidate for successful IBD management.

  19. Tumor necrosis factor α inhibits expression of the iron regulating hormone hepcidin in murine models of innate colitis.

    Directory of Open Access Journals (Sweden)

    Nanda Kumar N Shanmugam

    Full Text Available Abnormal expression of the liver peptide hormone hepcidin, a key regulator of iron homeostasis, contributes to the pathogenesis of anemia in conditions such as inflammatory bowel disease (IBD. Since little is known about the mechanisms that control hepcidin expression during states of intestinal inflammation, we sought to shed light on this issue using mouse models.Hepcidin expression was evaluated in two types of intestinal inflammation caused by innate immune activation-dextran sulfate sodium (DSS-induced colitis in wild-type mice and the spontaneous colitis occurring in T-bet/Rag2-deficient (TRUC mice. The role of tumor necrosis factor (TNF α was investigated by in vivo neutralization, and by treatment of a hepatocyte cell line, as well as mice, with the recombinant cytokine. Expression and activation of Smad1, a positive regulator of hepcidin transcription, were assessed during colitis and following administration or neutralization of TNFα. Hepcidin expression progressively decreased with time during DSS colitis, correlating with changes in systemic iron distribution. TNFα inhibited hepcidin expression in cultured hepatocytes and non-colitic mice, while TNFα neutralization during DSS colitis increased it. Similar results were obtained in TRUC mice. These effects involved a TNFα-dependent decrease in Smad1 protein but not mRNA.TNFα inhibits hepcidin expression in two distinct types of innate colitis, with down-regulation of Smad1 protein playing an important role in this process. This inhibitory effect of TNFα may be superseded by other factors in the context of T cell-mediated colitis given that in the latter form of intestinal inflammation hepcidin is usually up-regulated.

  20. 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

  1. Microscopic colitis: A literature review

    Directory of Open Access Journals (Sweden)

    ANA PAULA HAMER SOUSA CLARA

    Full Text Available SUMMARY Microscopic colitis (MC refers to chronic inflammation of the colon which is characterized by histologic changes at the level of a radiologically and endoscopically normal mucosa. It is a common cause of chronic non-bloody diarrhea that occurs primarily in older individuals; however, there are few studies in the literature with strong scientific evidence compared to other inflammatory bowel diseases (IBD, which limits the knowledge of physicians and pathologists. This article aims to review the information on MC, describing diagnostic methods and drugs available for treatment. We conducted a search of the Pubmed database and CAPES Portal using the keywords “microscopic colitis”, “collagenous colitis”, “lymphocytic colitis”, and “review” for selection of articles published between 1996 and 2015 related to the topic. Based on the studies discussed in this review, we conclude that MC is a relatively new gastrointestinal disorder, most studies are incipient particularly with respect to pathophysiology and immunology, and budesonide is the best documented short-term treatment. However, further studies are needed to elucidate the best strategy for treatment in the long term.

  2. Cannabinoids Receptor-2 (CB2) agonist ameliorates colitis in IL-10−/− mice by attenuating the activation of T cells and promoting their apoptosis

    Science.gov (United States)

    Singh, Udai P.; Singh, Narendra P.; Singh, Balwan; Price, Robert L.; Nagarkatti, Mitzi; Nagarkatti, Prakash S.

    2014-01-01

    Inflammatory bowel disease (IBD) is a chronic intestinal inflammation caused by hyperactivated effector immune cells that produce pro-inflammatory cytokines. Recent studies have shown that the cannabinoid system may play a critical role in mediating protection against intestinal inflammation. However, the effect of cannabinoid receptors induction after chronic colitis progression has not been investigated. Here, we investigate the effect of cannabinoid receptor-2 (CB2) agonist, JWH-133, after chronic colitis in IL-10−/− mice. JWH-133 effectively attenuated the overall clinical score, reversed colitis-associated pathogenesis and decrease in body weight in IL-10−/− mice. After JWH-133 treatment, the percentage of CD4+ T cells, neutrophils, mast cells, natural killer (NK1.1) cells, and activated T cells in the LP of colitis mice declined after JWH-133 treatment in the intestinal lamina propria (LP) and mesenteric lymph nodes (MLN). JWH-133 was also effective in ameliorating dextran sodium sulphate (DSS)-induced colitis. In this model, JWH-133 reduced the number and percentage of macrophages and IFN-γ expressing cells that were induced during colitis progression. Treatment with aminoalkylindole 6-iodopravadoline (AM630), a CB2 receptor antagonist, reversed the colitis protection provided by JWH-133 treatment. Also, activated T cells were found to undergo apoptosis following JWH-133 treatment both in-vivo and in-vitro. These findings suggest that JWH-133 mediates its effect through CB2 receptors, and ameliorates chronic colitis by inducing apoptosis in activated T cells, reducing the numbers of activated T cells, suppressing induction of mast cells, NK cells, and neutrophils at sites of inflammation in the LP. These results support the idea that the CB2 receptor agonists may serve as a therapeutic modality against IBD. PMID:22119709

  3. Fulminant postcesarean Clostridium difficile pseudomembranous colitis.

    Science.gov (United States)

    Ghai, Sonia; Ghai, Vikas; Sunderji, Shiraz

    2007-02-01

    Pseudomembranous colitis due to Clostridium difficile infection is rarely reported in the obstetric literature. This disease process is associated with prior antibiotic exposure. A term primigravida was delivered by primary cesarean for failed vacuum extraction. She received Intravenous cefazolin after cord clamping, which was continued for 36 hours for a presumptive diagnosis of endometritis. On day 3, oral amoxicillin and clavulanate was started for suspected cellulitis of the incision. She was readmitted 1 day after her discharge with severe diffuse abdominal pain and distention. Proctoscopy showed pseudomembranous colitis. Colectomy with temporary ileostomy was performed for worsening symptoms and imminent perforation. The diagnosis of pseudomembranous colitis should be considered in postpartum women who have low-grade fever, abdominal and gastrointestinal symptoms, and recent antibiotic exposure.

  4. Clostridium difficile colitis: A clinical review.

    Science.gov (United States)

    Ong, Gabie K B; Reidy, Tobi J; Huk, Matthew D; Lane, Frederick R

    2017-03-01

    Clostridium difficile colitis is an important cause of morbidity and mortality in the surgical patient. In recent years, Clostridium difficile infections have shown marked increases in frequency, severity, and resistance to standard treatment. With urgent operative interventions and novel endoscopic approaches, pseudomembranous colitis is being seen more commonly in surgical practices. In this paper, we will review a number of papers from the literature. We will discuss the epidemiology, evaluation and treatment of Clostridium difficile infection. Fulminant colitis may require emergency operation. For the surgical endoscopist, fecal microbiota transplantation restores the gastrointestinal flora, and has been shown to be effective in more than 80% of patients. Clostridium difficile infection is a major cause of healthcare-related diarrhea leading to increased morbidity and mortality in surgical patients. Increases in failure rates and resistance to current treatments are clinical and economic challenges in the healthcare situation. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Epithelial apoptosis: cause or consequence of ulcerative colitis?

    DEFF Research Database (Denmark)

    Seidelin, Jakob Benedict; Nielsen, Ole Haagen

    2009-01-01

    OBJECTIVE: Epithelial apoptosis rates are increased in ulcerative colitis (UC). The increased apoptosis rate could expose mucosal cells to luminal pathogens and thereby be regarded as a primary pathogenic factor in UC. On the other hand, the local inflammatory reaction could cause epithelial...... apoptosis secondary to the release of cytotoxic mediators. If apoptosis is a primary defect, apoptosis rates could influence the degree of spreading of inflammation and the clinical course of UC. If apoptosis is a side effect of local inflammation, apoptosis rates would be expected only to correlate...... with the degree of local inflammation. The aim of the study was to investigate the relationship between epithelial apoptosis and clinical characteristics of UC. MATERIAL AND METHODS: Twenty patients with UC (12 with active disease) and 20 control subjects were included. Freshly isolated colonic epithelial cells...

  6. Dietary aloin, aloesin, or aloe-gel exerts anti-inflammatory activity in a rat colitis model.

    Science.gov (United States)

    Park, Mi-Young; Kwon, Hoon-Jeong; Sung, Mi-Kyung

    2011-03-14

    Aloe has been a very popular folk remedy for inflammation-related pathological conditions despite the lack of studies reporting its efficacy in vivo. The present study evaluated the anti-inflammatory effects of aloe components (aloin, aloesin and aloe-gel) known to be biologically active in the rat model of colitis. Male Sprague Dawley rats were fed experimental diets for 2 weeks before and during the induction of colitis. Drinking water containing 3% dextran sulfate sodium (DSS) was provided for 1 week to induce colitis. At the end of the experimental period, clinical and biochemical markers were compared. Plasma leukotriene B(4) (LTB(4)) and tumor necrosis factor-α (TNF-α) concentrations were significantly decreased in all groups supplemented with aloe components compared to the colitis control group (paloin, aloesin, or aloe-gel (p<0.05). Dietary supplementation of aloe components ameliorates intestinal inflammatory responses in a DSS-induced ulcerative colitis rat model. In particular, aloesin was the most potent inhibitor. Further studies are required for a more complete understanding of the specific mechanism of the action of these supplements. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. Different Effects of Three Selected Lactobacillus Strains in Dextran Sulfate Sodium-Induced Colitis in BALB/c Mice.

    Science.gov (United States)

    Cui, Yi; Wei, Hongyun; Lu, Fanggen; Liu, Xiaowei; Liu, Deliang; Gu, Li; Ouyang, Chunhui

    2016-01-01

    To analyze the changes of different Lactobacillus species in ulcerative colitis patients and to further assess the therapeutic effects of selected Lactobacillus strains on dextran sulfate sodium (DSS)-induced experimental colitis in BALB/c mice. Forty-five active ulcerative colitis (UC) patients and 45 population-based healthy controls were enrolled. Polymerase chain reaction (PCR) amplification and real-time PCR were performed for qualitative and quantitative analyses, respectively, of the Lactobacillus species in UC patients. Three Lactobacillus strains from three species were selected to assess the therapeutic effects on experimental colitis. Sixty 8-week-old BALB/c mice were divided into six groups. The five groups that had received DSS were administered normal saline, mesalazine, L. fermentum CCTCC M206110 strain, L. crispatus CCTCC M206119 strain, or L. plantarum NCIMB8826 strain. We assessed the severity of colitis based on disease activity index (DAI), body weight loss, colon length, and histologic damage. The detection rate of four of the 11 Lactobacillus species decreased significantly (P weight loss and colon length shortening, lower DAI scores, and lower histologic scores (P weight loss and colon length shortening, higher histologic scores, and more severe inflammatory infiltration (P weight loss and colon length shortening (P probiotic effect of L. plantarum NCIMB8826 on UC has yet to be assessed.

  8. [Microscopic colitis--new insights relevant to clinical practice].

    Science.gov (United States)

    Miehlke, S; Aust, D; Madisch, A

    2013-12-01

    Microscopic colitis is an increasingly recognised chronic inflammatory bowel disease associated with watery, non-bloody diarrhoea. In addition, many patients suffer from abdominal pain, nocturnal diarrhoea, urgency and incontinence. The two traditional histological subtypes are collagenous colitis and lymphocytic colitis. A novel third subgroup is the so-called incomplete microscopic colitis which is clinically indistinguishable. At present, budesonide is the only evidenced-based effective therapy, however many problems in the long-term treatment strategy are still unsolved. The present paper reviews new developments in microscopic colitis which are relevant for clinical practice. © Georg Thieme Verlag KG Stuttgart · New York.

  9. Lack of adrenomedullin results in microbiota changes and aggravates azoxymethane and dextran sulfate sodium-induced colitis in mice

    Directory of Open Access Journals (Sweden)

    Sonia Martinez-Herrero

    2016-11-01

    Full Text Available The link between intestinal inflammation, microbiota, and colorectal cancer (CRC is intriguing and the potential underlying mechanisms remain unknown. Here we evaluate the influence of adrenomedullin (AM in microbiota composition and its impact on colitis with an inducible knockout (KO mouse model for AM. Microbiota composition was analyzed in KO and wild type (WT mice by pyrosequencing. Colitis was induced in mice by administration of azoxymethane (AOM followed by dextran sulfate sodium (DSS in the drinking water. Colitis was evaluated using a clinical symptoms index, histopathological analyses, and qRT-PCR. Abrogation of the adm gene in the whole body was confirmed by PCR and qRT-PCR. KO mice exhibit significant changes in colonic microbiota: higher proportion of δ-Proteobacteria class; of Coriobacteriales order; and of other families and genera was observed in KO feces. Meanwhile these mice had a lower proportion of beneficial bacteria, such as Lactobacillus gasseri and Bifidobacterium choerinum. TLR4 gene expression was higher (p<0.05 in KO animals. AM deficient mice treated with DSS exhibited a significantly worse colitis with profound weight loss, severe diarrhea, rectal bleeding, colonic inflammation, edema, infiltration, crypt destruction, and higher levels of pro-inflammatory cytokines. No changes were observed in the expression levels of adhesion molecules. In conclusion, we have shown that lack of AM leads to changes in gut microbiota population and in a worsening of colitis conditions, suggesting that endogenous AM is a protective mediator in this pathology.

  10. In-vivo monitoring of acute DSS-Colitis using Colonoscopy, high resolution Ultrasound and bench-top Magnetic Resonance Imaging in Mice

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    Walldorf, J.; Hermann, M.; Pohl, S.; Zipprich, A. [Martin Luther University Halle-Wittenberg, Department of Internal Medicine I, Halle (Germany); Porzner, M.; Seufferlein, T. [University of Ulm, Department of Internal Medicine I, Ulm (Germany); Metz, H.; Maeder, K. [Martin Luther University, Institut of Pharmacy, Halle-Wittenberg (Germany); Christ, B. [University of Leipzig, Department of Surgery II, Leipzig (Germany)

    2015-10-15

    The aim of this study was to establish and evaluate (colour Doppler-) high-resolution-ultrasound (hrUS) and bench-top magnetic resonance imaging (btMRI) as new methods to monitor experimental colitis. hrUS, btMRI and endoscopy were performed in mice without colitis (n = 15), in mice with acute colitis (n = 14) and in mice with acute colitis and simultaneous treatment with infliximab (n = 19). Determination of colon wall thickness using hrUS (32 MHz) and measurement of the cross-sectional colonic areas by btMRI allowed discrimination between the treatment groups (mean a vs. b vs. c - btMRI: 922 vs. 2051 vs. 1472 pixel, hrUS: 0.26 vs. 0.45 vs. 0.31 mm). btMRI, endoscopy, hrUS and colour Doppler-hrUS correlated to histological scoring (p < 0.05), while endoscopy and btMRI correlated to post-mortem colon length (p < 0.05). The innovative in vivo techniques btMRI and hrUS are safe and technically feasible. They differentiate between distinct grades of colitis in an experimental setting, and correlate with established post-mortem parameters. In addition to endoscopic procedures, these techniques provide information regarding colon wall thickness and perfusion. Depending on the availability of these techniques, their application increases the value of in vivo monitoring in experimental acute colitis in small rodents. (orig.)

  11. Cerebral demyelination in children with collagenous colitis

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    S Sankararaman

    2013-01-01

    Full Text Available Collagenous colitis (CC is a form of microscopic colitis characterized by the presence of inflammatory infiltrate and subepithelial deposition of collagen in the colon and it is a rare condition with a predominant prevalence in the adult population. Only few cases have been reported in children. We report two children with the CC with concomitant neurological manifestations. Both cases demonstrated variable neurological symptoms clinically and significant cerebral demyelination. In both patients, the gastrointestinal manifestations drastically improved with a short course of prednisolone. However, the neurological symptoms were persistent and progressive. To the best of our knowledge, similar association has not been reported in children.

  12. Diagnosis and Management of Microscopic Colitis.

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    Pardi, Darrell S

    2017-01-01

    Microscopic colitis (MC) is a relatively common cause of chronic watery diarrhea, especially in older persons. Associated symptoms, including abdominal pain and arthralgias, are common. The diagnosis is based upon characteristic histological findings in the presence of diarrhea. The two types of MC, collagenous and lymphocytic colitis, share similar clinical features, with the main difference being the presence or absence of a thickened subepithelial collagen band. There are several treatment options for patients with MC, although only budesonide has been well studied in multiple controlled clinical trials. This review will describe the clinical features, epidemiology, pathophysiology, diagnostic criteria, and treatment of patients with MC.

  13. Optimal management of steroid-dependent ulcerative colitis

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    Khan HMW

    2015-11-01

    Full Text Available Hafiz M Waqas Khan,1 Faisal Mehmood,1 Nabeel Khan2 1Department of Medicine, King Edward Medical University, Lahore, Pakistan; 2Section of Gastroenterology, University of Pennsylvania Perelman School of Medicine, Philadelphia VA Medical Center, Philadelphia, PA, USA Abstract: Ulcerative colitis (UC is a chronic inflammatory condition that is variable in both extent and severity of disease as well as response to therapy. Corticosteroids (CSs were the first drugs used in the management of UC and are still used for induction of remission. However, because of their extensive side-effect profile, they are not utilized for maintenance of remission. In view of this, CS-free remission has become an important end point while evaluating therapeutic agents used in the management of UC. This review highlights the results of various studies conducted to evaluate the efficacy of different medications to attain CS-free remission in the setting of active UC. The drugs reviewed include established agents such as thiopurines, methotrexate, infliximab, adalimumab, vedolizumab, golimumab, and newer experimental agents, and if all else fails, colectomy will be performed. The efficacy of these drugs is evaluated individually. Our aim is to provide a synopsis of the work done in this field to date. Keywords: ulcerative colitis, steroid dependent, thiopurines, MTX, adalimumab, infliximab

  14. Comparative Effect of the I3.1 Probiotic Formula in Two Animal Models of Colitis.

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    Lorén, Violeta; Manyé, Josep; Fuentes, Mari C; Cabré, Eduard; Ojanguren, Isabel; Espadaler, Jordi

    2017-03-01

    Use of probiotic therapy is an active area of investigation to treat intestinal disorders. The clinical benefits of the I3.1 probiotic formula (Lactobacillus plantarum (CECT7484, CECT7485) and P. acidilactici (CECT7483)) were demonstrated in irritable bowel syndrome (IBS) patients in a randomized, double-blind, placebo-controlled clinical trial. The aim of this study was to evaluate the therapeutic effects of I3.1 in two experimental models of colitis, a dextran sulfate sodium (DSS)-induced colitis model and an interleukin (IL)-10-deficient mice model. Colitis was induced in 32 8-week-old Balb/c mice by administering 3% (w/v) DSS in drinking water for 5 days. Probiotics were administered orally (I3.1 or VSL#3, 1 × 109 CFU daily) for 10 days before the administration of DSS. Also, probiotics (I3.1 or VSL#3, 1 × 109 CFU daily) were administered orally to 36 6-week-old C57B6J IL-10(-/-) mice for 10 weeks. Body weight was recorded daily. Colon samples were harvested for histological examination and cytokine measurements. Body weight after DSS administration did not change in the I3.1 group, whereas the VSL#3 group had weight loss. Also, I3.1 normalized IL-6 to levels similar to that of healthy controls and significantly increased the reparative histologic score. In the IL-10-deficient model, both VSL#3 and I3.1 reduced the severity of colitis compared to untreated controls, and I3.1 significantly reduced the levels of IFN-γ compared to the other two groups. In conclusion, I3.1 displays a protective effect on two murine models of experimental colitis. Results suggest that the mechanism of action could be different from VSL#3.

  15. Hydrogen peroxide scavenger, catalase, alleviates ion transport dysfunction in murine colitis.

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    Barrett, Kim E; McCole, Declan F

    2016-11-01

    Reactive oxygen species (ROS) such as hydrogen peroxide (H2 O2 ) contribute to epithelial damage and ion transport dysfunction (key events in inflammatory diarrhoea) in inflammatory bowel disease (IBD). The aim of this study was to identify if H2 O2 mediates suppression of colonic ion transport function in the murine dextran sulfate sodium (DSS) colitis model by using the H2 O2 degrading enzyme, catalase. Colitis was induced by administering DSS (4%) in drinking water for 5 days followed by 3 days on normal H2 O. Mice were administered either pegylated catalase or saline at day -1, 0 and +1 of DSS treatment. Ion transport responses to the Ca2+ -dependent agonist, carbachol (CCh), or the cAMP-dependent agonist, forskolin, were measured across distal colonic mucosa mounted in Ussing chambers. Parameters of DSS-induced inflammation (loss in body weight, decreased colon length, altered stool consistency), were only partially alleviated by catalase while histology was only minimally improved. However, catalase significantly reversed the DSS-induced reduction in baseline ion transport as well as colonic Isc responses to CCh. However, ion transport responses to forskolin were not significantly restored. Catalase also reduced activation of ERK MAP kinase in the setting of colitis, and increased expression of the Na+ -K+ -2Cl- cotransporter, NKCC1, consistent with restoration of ion transport function. Ex vivo treatment of inflamed colonic mucosae with catalase also partially restored ion transport function. Therefore, catalase partially prevents, and rescues, the loss of ion transport properties in DSS colitis even in the setting of unresolved tissue inflammation. These findings indicate a prominent role for ROS in ion transport dysfunction in colitis and may suggest novel strategies for the treatment of inflammatory diarrhoea. © 2016 John Wiley & Sons Australia, Ltd.

  16. Lymphocytic and collagenous colitis: an overview of so-called microscopic colitis.

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    Chetty, Runjan; Govender, Dhirendra

    2012-02-21

    The entity of 'microscopic colitis' is being diagnosed with increasing frequency and is a well-established clinicopathological diagnosis that is underpinned by a triad of watery diarrhea, normal results on endoscopy and characteristic microscopic findings. Careful histopathological evaluation and awareness of its numerous associations (especially with drugs and celiac disease) and mimics will lead to the correct diagnosis of microscopic colitis. The etiology of microscopic colitis remains enigmatic and is multifactorial with different elements being more influential in different individuals. Treatment includes antidiarrheal agents and anti-inflammatory drugs (including steroids). The purpose of this article is to provide some clarity on nomenclature, discuss the multitude of conditions that can occur synchronously or metachronously with microscopic colitis and their role in the etiopathogenesis of this condition, provide a detailed review of the pathological aspects of the disease and to briefly discuss treatment trends.

  17. Irsogladine maleate ameliorates inflammation and fibrosis in mice with chronic colitis induced by dextran sulfate sodium.

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    Yamaguchi, Hana; Suzuki, Kenji; Nagata, Masaki; Kawase, Tomoyuki; Sukumaran, Vijayakumar; Thandavarayan, Rajarajan A; Kawauchi, Yusuke; Yokoyama, Junji; Tomita, Masayuki; Kawachi, Hiroshi; Watanabe, Kenichi; Yoneyama, Hiroyuki; Asakura, Hitoshi; Takagi, Ritsuo

    2012-06-01

    Intestinal fibrosis is a common and severe complication of inflammatory bowel disease (IBD), especially Crohn's disease (CD). To investigate the therapeutic approach to intestinal fibrosis, we have developed a mouse model of intestinal fibrosis by administering dextran sulfate sodium (DSS) and examining the effects of irsogladine maleate (IM) [2,4-diamino-6-(2,5-dichlorophenyl)-s-triazine maleate], which has been widely used as an antiulcer drug for gastric mucosa in Japan, on DDS-induced chronic colitis. In this experimental colitis lesion, several pathognomonic changes were found: increased deposition of collagen, increased number of profibrogenic mesenchymal cells such as fibroblasts (vimentin(+), α-SMA(-)) and myofibroblasts (vimentin(+), α-SMA(+)) in both mucosa and submucosa of the colon with infiltrating inflammatory cells, and increased mRNA expressions of collagen type I, transforming growth factor (TGF)-β, matrix metalloproteinase (MMP)-2, and tissue inhibitor of matrix metalloproteinase (TIMP)-1. When IM was administered intrarectally to this colitis, all these pathological changes were significantly decreased or suppressed, suggesting a potential adjunctive therapy for intestinal fibrosis. IM could consequently reduce fibrosis in DSS colitis by direct or indirect effect on profibrogenic factors or fibroblasts. Therefore, the precise effect of IM on intestinal fibrosis should be investigated further.

  18. Magnolol, a Natural Polyphenol, Attenuates Dextran Sulfate Sodium-Induced Colitis in Mice

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    Ling Zhao

    2017-07-01

    Full Text Available Magnolol is a lignan with anti-inflammatory activity identified in Magnolia officinalis. Ulcerative colitis (UC, one of the types of inflammatory bowel disease (IBD, is a disease that causes inflammation and ulcers in the colon. To investigate the effect of magnolol in dextran sulfate sodium (DSS-induced experimental UC model, male C57 mice were treated with 2% DSS drinking water for 5 consecutive days followed by intragastric administration with magnolol (5, 10 and 15 mg/kg daily for 7 days. The results showed that magnolol significantly attenuated disease activity index, inhibited colonic shortening, reduced colonic lesions and suppressed myeloperoxidase (MPO activity. Moreover, colonic pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β induced by colitis were dramatically decreased by magnolol. To further unveil the metabolic signatures upon magnolol treatment, mass spectrometry-based metabolomic analysis of the small molecular metabolites in mice serum were performed. Compared with controls, abnormality of serum metabolic phenotypes in DSS-treated mice were effectively reversed by different doses of magnolol. In particular, magnolol treatment effectively elevated the serum levels of tryptophan metabolites including kynurenic acid (KA, 5-hydroxyindoleacetic acid, indoleacetic acid (IAA, indolelactic acid and indoxylsulfuric acid, which are potential aryl hydrocarbon receptor (AHR ligands to impact colitis. These findings suggest that magnolol exerts anti-inflammatory effect on DSS-induced colitis and its underlying mechanisms are associated with the restoring of tryptophan metabolites that inhibit the colonic inflammation.

  19. Strontium Chloride: Can It Be a New Treatment Option for Ulcerative Colitis?

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    Topal, Firdevs; Yonem, Ozlem; Tuzcu, Mehmet; Ataseven, Hilmi; Akyol, Melih

    2014-01-01

    Background/Aims. Patients with ulcerative colitis still need effective therapy without major side effects. It has been found that strontium can suppress NFκB activation induced by TNF-α. This opens a gate to a new anti-TNF agent which is cheap and can be given orally. We for the first time aimed to investigate the effect of strontium chloride (SrCl2) on inflammation in experimental colitis. Methods. Thirty female Wistar albino rats were divided into 5 groups each containing 6 rats. The rats in groups 1 and 2 served as the healthy control and colitis group, respectively. The rats in groups 3, 4, and 5 had colitis and received 40 mg/kg SrCl2, 160 mg/kg SrCl2, and 1 mg/kg prednisolone by oral gavage, respectively. The rats were sacrificed for histological evaluation and determination of serum neopterin, TNF-α, and IFN-γ levels. Results. The neopterin, TNF-α and IFNγ levels of group 2 was significantly higher than the other groups. The neopterin, TNF-α, and IFN-γ levels of controls and other treatment groups were comparable. There were a significant difference in macroscopic and microscopic healing between group 2 and other groups histologically. But there was not a significant difference within treatment receiving groups. Conclusion. SrCl2 had comparable therapeutic efficiency with prednisolone. PMID:25032214

  20. Strontium Chloride: Can It Be a New Treatment Option for Ulcerative Colitis?

    Directory of Open Access Journals (Sweden)

    Firdevs Topal

    2014-01-01

    Full Text Available Background/Aims. Patients with ulcerative colitis still need effective therapy without major side effects. It has been found that strontium can suppress NFκB activation induced by TNF-α. This opens a gate to a new anti-TNF agent which is cheap and can be given orally. We for the first time aimed to investigate the effect of strontium chloride (SrCl2 on inflammation in experimental colitis. Methods. Thirty female Wistar albino rats were divided into 5 groups each containing 6 rats. The rats in groups 1 and 2 served as the healthy control and colitis group, respectively. The rats in groups 3, 4, and 5 had colitis and received 40 mg/kg SrCl2, 160 mg/kg SrCl2, and 1 mg/kg prednisolone by oral gavage, respectively. The rats were sacrificed for histological evaluation and determination of serum neopterin, TNF-α, and IFN-γ levels. Results. The neopterin, TNF-α and IFNγ levels of group 2 was significantly higher than the other groups. The neopterin, TNF-α, and IFN-γ levels of controls and other treatment groups were comparable. There were a significant difference in macroscopic and microscopic healing between group 2 and other groups histologically. But there was not a significant difference within treatment receiving groups. Conclusion. SrCl2 had comparable therapeutic efficiency with prednisolone.