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Sample records for alleviates intestinal inflammation

  1. Mechanisms involved in alleviation of intestinal inflammation by bifidobacterium breve soluble factors.

    Directory of Open Access Journals (Sweden)

    Elise Heuvelin

    Full Text Available OBJECTIVES: Soluble factors released by Bifidobacterium breve C50 (Bb alleviate the secretion of pro-inflammatory cytokines by immune cells, but their effect on intestinal epithelium remains elusive. To decipher the mechanisms accounting for the cross-talk between bacteria/soluble factors and intestinal epithelium, we measured the capacity of the bacteria, its conditioned medium (Bb-CM and other Gram(+ commensal bacteria to dampen inflammatory chemokine secretion. METHODS: TNFalpha-induced chemokine (CXCL8 secretion and alteration of NF-kappaB and AP-1 signalling pathways by Bb were studied by EMSA, confocal microscopy and western blotting. Anti-inflammatory capacity was also tested in vivo in a model of TNBS-induced colitis in mice. RESULTS: Bb and Bb-CM, but not other commensal bacteria, induced a time and dose-dependent inhibition of CXCL8 secretion by epithelial cells driven by both AP-1 and NF-kappaB transcription pathways and implying decreased phosphorylation of p38-MAPK and IkappaB-alpha molecules. In TNBS-induced colitis in mice, Bb-CM decreased the colitis score and inflammatory cytokine expression, an effect reproduced by dendritic cell conditioning with Bb-CM. CONCLUSIONS: Bb and secreted soluble factors contribute positively to intestinal homeostasis by attenuating chemokine production. The results indicate that Bb down regulate inflammation at the epithelial level by inhibiting phosphorylations involved in inflammatory processes and by protective conditioning of dendritic cells.

  2. Lychee (Litchi chinensis Sonn.) Pulp Phenolic Extract Provides Protection against Alcoholic Liver Injury in Mice by Alleviating Intestinal Microbiota Dysbiosis, Intestinal Barrier Dysfunction, and Liver Inflammation.

    Science.gov (United States)

    Xiao, Juan; Zhang, Ruifen; Zhou, Qiuyun; Liu, Lei; Huang, Fei; Deng, Yuanyuan; Ma, Yongxuan; Wei, Zhencheng; Tang, Xiaojun; Zhang, Mingwei

    2017-11-08

    Liver injury is the most common consequence of alcohol abuse, which is promoted by the inflammatory response triggered by gut-derived endotoxins produced as a consequence of intestinal microbiota dysbiosis and barrier dysfunction. The aim of this study was to investigate whether modulation of intestinal microbiota and barrier function, and liver inflammation contributes to the hepatoprotective effect of lychee pulp phenolic extract (LPPE) in alcohol-fed mice. Mice were treated with an ethanol-containing liquid diet alone or in combination with LPPE for 8 weeks. LPPE supplementation alleviated ethanol-induced liver injury and downregulated key markers of inflammation. Moreover, LPPE supplementation reversed the ethanol-induced alteration of intestinal microbiota composition and increased the expression of intestinal tight junction proteins, mucus protecting proteins, and antimicrobial proteins. Furthermore, in addition to decreasing serum endotoxin level, LPPE supplementation suppressed CD14 and toll-like receptor 4 expression, and repressed the activation of nuclear factor-κB p65 in the liver. These data suggest that intestinal microbiota dysbiosis, intestinal barrier dysfunction, and liver inflammation are improved by LPPE, and therefore, the intake of LPPE or Litchi pulp may be an effective strategy to alleviate the susceptibility to alcohol-induced hepatic diseases.

  3. GLP-1 nanomedicine alleviates gut inflammation.

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    Anbazhagan, Arivarasu N; Thaqi, Mentor; Priyamvada, Shubha; Jayawardena, Dulari; Kumar, Anoop; Gujral, Tarunmeet; Chatterjee, Ishita; Mugarza, Edurne; Saksena, Seema; Onyuksel, Hayat; Dudeja, Pradeep K

    2017-02-01

    The gut hormone, glucagon like peptide-1 (GLP-1) exerts anti-inflammatory effects. However, its clinical use is limited by its short half-life. Previously, we have shown that GLP-1 as a nanomedicine (GLP-1 in sterically stabilized phospholipid micelles, GLP-1-SSM) has increased in vivo stability. The current study was aimed at testing the efficacy of this GLP-1 nanomedicine in alleviating colonic inflammation and associated diarrhea in dextran sodium sulfate (DSS) induced mouse colitis model. Our results show that GLP-1-SSM treatment markedly alleviated the colitis phenotype by reducing the expression of pro-inflammatory cytokine IL-1β, increasing goblet cells and preserving intestinal epithelial architecture in colitis model. Further, GLP-1-SSM alleviated diarrhea (as assessed by luminal fluid) by increasing protein expression of intestinal chloride transporter DRA (down regulated in adenoma). Our results indicate that GLP-1 nanomedicine may act as a novel therapeutic tool in alleviating gut inflammation and associated diarrhea in inflammatory bowel disease (IBD). Published by Elsevier Inc.

  4. Cytokines and intestinal inflammation.

    Science.gov (United States)

    Bamias, Giorgos; Cominelli, Fabio

    2016-11-01

    Cytokines of the intestinal microenvironment largely dictate immunological responses after mucosal insults and the dominance of homeostatic or proinflammatory pathways. This review presents important recent studies on the role of specific cytokines in the pathogenesis of intestinal inflammation. The particular mucosal effects of cytokines depend on their inherent properties but also the cellular origin, type of stimulatory antigens, intermolecular interactions, and the particular immunological milieu. Novel cytokines of the interleukin-1 (IL-1) family, including IL-33 and IL-36, have dominant roles in mucosal immunity, whereas more established ones such as IL-18 are constantly enriched with unique properties. Th17 cells are important mucosal constituents, although their profound plasticity, makes the specific set of cytokines they secrete more important than their mere numbers. Finally, various cytokines, such as tumor necrosis factor-α, IL-6, tumor necrosis factor-like cytokine 1A, and death receptor, 3 demonstrate dichotomous roles with mucosa-protective function in acute injury but proinflammatory effects during chronic inflammation. The role of cytokines in mucosal health and disease is increasingly revealed. Such information not only will advance our understanding of the pathogenesis of gut inflammation, but also set the background for development of reliable diagnostic and prognostic biomarkers and cytokine-specific therapies.

  5. Exercise alleviates depression related systemic inflammation in ...

    African Journals Online (AJOL)

    sion, however our understanding of how to use exercise effectively in COPD patients to alleviate depression related systemic inflammation is incomplete ... bidities (i.e. cardiovascular disease risk factors and glyce- mic control). A prospective ..... T, Ross R. An exercise intervention without weight loss. African Health Sciences ...

  6. Reishi Protein LZ-8 Induces FOXP3+ Treg Expansion via a CD45-Dependent Signaling Pathway and Alleviates Acute Intestinal Inflammation in Mice

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    Hsien-Yeh Hsu

    2013-01-01

    Full Text Available LZ-8, an immunomodulatory protein isolated from Ganoderma lucidum (also known as Ling-Zhi or Reishi, has been shown to promote cell proliferation and IL-2 production in T cells. In this study, we show that LZ-8 induces the expansion of both murine and human CD4+ T cells into FOXP3+ regulatory T (Treg cells. LZ-8 treatment was found to stimulate a 4-fold and a 10-fold expansion in the Treg populations of murine and human primary CD4+ T cells, respectively. In addition, the expression of CTLA-4 and IL-10 was induced in LZ-8-treated CD4+ T cells. Using neutralizing antibodies and gene-deficient T-cell lines, we also found that LZ-8 promotes Treg expansion through a CD45-mediated signaling pathway and that the CD18-dependent induction of IL-2 was involved in Treg formation and IL-10 production. The suppressive activity of LZ-8 was confirmed using a murine model of DSS-induced colitis; the disease was alleviated by the adoptive transfer of LZ-8-treated CD4+ T cells. In conclusion, a new regulatory function for LZ-8 was identified, and the molecular mechanisms underlying this function were elucidated.

  7. Co-administration of a probiotic strain Lactobacillus plantarum LS/07 CCM7766 with prebiotic inulin alleviates the intestinal inflammation in rats exposed to N,N-dimethylhydrazine.

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    Štofilová, Jana; Szabadosová, Viktória; Hrčková, Gabriela; Salaj, Rastislav; Bertková, Izabela; Hijová, Emília; Strojný, Ladislav; Bomba, Alojz

    2015-02-01

    The aim of this study was to determine the anti-inflammatory effects of preventive administration of a probiotic strain Lactobacillus plantarum LS/07 CCM7766 alone or in combination with prebiotic inulin or with flax-seed oil in the gut of rats, which developed chronic inflammation following administration of the pro-carcinogen N,N-dimethylhydrazine (DMH). After 28weeks administration of probiotic/prebiotic-containing diet, rats were killed and their colons were examined by immunohistological criteria, whereas cytokines were determined in the jejunal mucosa. Application of DMH triggered the production of pro-inflammatory cytokines IL-2, IL-6, IL-17, and TNF-α, expression of pro-inflammatory mediators NF-κB, COX-2 and iNOS and caused depletion of goblet cells. Supplementing the diet with L. plantarum and its combination with the prebiotic abolished DMH-induced inflammatory process in the jejunal mucosa by inhibiting the production of pro-inflammatory cytokines and by stimulation of anti-inflammatory IL-10 cytokine synthesis, whereas concentration of TGF-β1 was not influenced significantly. Diet prevented a decrease in goblet cell numbers but numbers of mast cells were lowered only moderately. However, combined treatment of rats with L. plantarum and flax-seed oil had no significant effect on the parameters examined, except for decreased expression of NF-κB, in comparison with the negative control. Results indicate that the preventive administration of probiotic L. plantarum LS/07 CCM7766 alone or in combination with prebiotic inulin to rats with DMH-induced chronic inflammation can reduce inflammatory process in the jejunal and colon mucosa, probably indirectly, and involves down-regulation of synthesis of pro-inflammatory cytokines and suppression of NF-κB activity in mucosal cells. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Exercise alleviates depression related systemic inflammation in ...

    African Journals Online (AJOL)

    Objective: The aim of this study was to measure the changes in depression related systemic inflammation of aerobic exercise training in COPD patients in Jeddah area. Material and methods: Eighty patients with moderate severity of COPD participated in this study and were divided into two groups; the first group received ...

  9. Intestinal parasites : associations with intestinal and systemic inflammation

    NARCIS (Netherlands)

    Zavala, Gerardo A; García, Olga P; Camacho, Mariela; Ronquillo, Dolores; Campos-Ponce, Maiza; Doak, Colleen; Polman, Katja; Rosado, Jorge L

    2018-01-01

    AIMS: Evaluate associations between intestinal parasitic infection with intestinal and systemic inflammatory markers in school-aged children with high rates of obesity. METHODS AND RESULTS: Plasma concentrations of CRP, leptin, TNF-α, IL-6 and IL-10 were measured as systemic inflammation markers and

  10. Dietary soy isoflavones alleviate dextran sulfate sodium-induced inflammation and oxidative stress in mice.

    Science.gov (United States)

    Wang, Bin; Wu, Cunbing

    2017-07-01

    It has been hypothesized that soy isoflavones exhibit anti-oxidative and anti-inflammatory functions, however, the effects of soy isoflavones on inflammatory bowel diseases remain unknown. Therefore, the present study aimed to investigate the effect and underlying mechanism of dietary soy isoflavones on dextran sulfate sodium (DSS)-induced colitis. Mice were administered DSS and soy isoflavones, and histomorphometry, oxidative stress, inflammation and intestinal tight junctions were determined. The current study demonstrated that dietary soy isoflavones alleviated DSS-induced growth suppression, colonic inflammatory response, oxidative stress and colonic barrier dysfunction. DSS treatment was indicated to activate Toll-like receptor 4 (TRL4) and myeloid differentiation protein 88 (MyD88) in mice, whereas dietary soy isoflavones inhibited Myd88 expression in DSS-challenged mice. In conclusion, dietary soy isoflavones alleviate DSS-induced inflammation in mice, which may be associated with enhancing antioxidant function and inhibiting the TLR4/MyD88 signal.

  11. Role of Smooth Muscle in Intestinal Inflammation

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    Stephen M Collins

    1996-01-01

    Full Text Available The notion that smooth muscle function is altered in inflammation is prompted by clinical observations of altered motility in patients with inflammatory bowel disease (IBD. While altered motility may reflect inflammation-induced changes in intrinsic or extrinsic nerves to the gut, changes in gut hormone release and changes in muscle function, recent studies have provided in vitro evidence of altered muscle contractility in muscle resected from patients with ulcerative colitis or Crohn’s disease. In addition, the observation that smooth muscle cells are more numerous and prominent in the strictured bowel of IBD patients compared with controls suggests that inflammation may alter the growth of intestinal smooth muscle. Thus, inflammation is associated with changes in smooth muscle growth and contractility that, in turn, contribute to important symptoms of IBD including diarrhea (from altered motility and pain (via either altered motility or stricture formation. The involvement of smooth muscle in this context may be as an innocent bystander, where cells and products of the inflammatory process induce alterations in muscle contractility and growth. However, it is likely that intestinal muscle cells play a more active role in the inflammatory process via the elaboration of mediators and trophic factors, including cytokines, and via the production of collagen. The concept of muscle cells as active participants in the intestinal inflammatory process is a new concept that is under intense study. This report summarizes current knowledge as it relates to these two aspects of altered muscle function (growth and contractility in the inflamed intestine, and will focus on mechanisms underlying these changes, based on data obtained from animal models of intestinal inflammation.

  12. Macrophages in intestinal homeostasis and inflammation

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    Bain, Calum C; Mowat, Allan McI

    2014-01-01

    The intestine contains the largest pool of macrophages in the body which are essential for maintaining mucosal homeostasis in the face of the microbiota and the constant need for epithelial renewal but are also important components of protective immunity and are involved in the pathology of inflammatory bowel disease (IBD). However, defining the biological roles of intestinal macrophages has been impeded by problems in defining the phenotype and origins of different populations of myeloid cells in the mucosa. Here, we discuss how multiple parameters can be used in combination to discriminate between functionally distinct myeloid cells and discuss the roles of macrophages during homeostasis and how these may change when inflammation ensues. We also discuss the evidence that intestinal macrophages do not fit the current paradigm that tissue-resident macrophages are derived from embryonic precursors that self-renew in situ, but require constant replenishment by blood monocytes. We describe our recent work demonstrating that classical monocytes constantly enter the intestinal mucosa and how the environment dictates their subsequent fate. We believe that understanding the factors that drive intestinal macrophage development in the steady state and how these may change in response to pathogens or inflammation could provide important insights into the treatment of IBD. PMID:24942685

  13. Functions and Signaling Pathways of Amino Acids in Intestinal Inflammation

    OpenAIRE

    Fang He; Chenlu Wu; Pan Li; Nengzhang Li; Dong Zhang; Quoqiang Zhu; Wenkai Ren; Yuanyi Peng

    2018-01-01

    Intestine is always exposed to external environment and intestinal microorganism; thus it is more sensitive to dysfunction and dysbiosis, leading to intestinal inflammation, such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and diarrhea. An increasing number of studies indicate that dietary amino acids play significant roles in preventing and treating intestinal inflammation. The review aims to summarize the functions and signaling mechanisms of amino acids in intestin...

  14. Topical Apigenin Alleviates Cutaneous Inflammation in Murine Models

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    Mao-Qiang Man

    2012-01-01

    Full Text Available Herbal medicines have been used in preventing and treating skin disorders for centuries. It has been demonstrated that systemic administration of chrysanthemum extract exhibits anti-inflammatory properties. However, whether topical applications of apigenin, a constituent of chrysanthemum extract, influence cutaneous inflammation is still unclear. In the present study, we first tested whether topical applications of apigenin alleviate cutaneous inflammation in murine models of acute dermatitis. The murine models of acute allergic contact dermatitis and acute irritant contact dermatitis were established by topical application of oxazolone and phorbol 12-myristate 13-acetate (TPA, respectively. Inflammation was assessed in both dermatitis models by measuring ear thickness. Additionally, the effect of apigenin on stratum corneum function in a murine subacute allergic contact dermatitis model was assessed with an MPA5 physiology monitor. Our results demonstrate that topical applications of apigenin exhibit therapeutic effects in both acute irritant contact dermatitis and allergic contact dermatitis models. Moreover, in comparison with the vehicle treatment, topical apigenin treatment significantly reduced transepidermal water loss, lowered skin surface pH, and increased stratum corneum hydration in a subacute murine allergic contact dermatitis model. Together, these results suggest that topical application of apigenin could provide an alternative regimen for the treatment of dermatitis.

  15. Icam-1 targeted nanogels loaded with dexamethasone alleviate pulmonary inflammation.

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    M Carme Coll Ferrer

    Full Text Available Lysozyme dextran nanogels (NG have great potential in vitro as a drug delivery platform, combining simple chemistry with rapid uptake and cargo release in target cells with "stealth" properties and low toxicity. In this work, we study for the first time the potential of targeted NG as a drug delivery platform in vivo to alleviate acute pulmonary inflammation in animal model of LPS-induced lung injury. NG are targeted to the endothelium via conjugation with an antibody (Ab directed to Intercellular Adhesion Molecule-1(ICAM-NG, whereas IgG conjugated NG (IgG-NG are used for control formulations. The amount of Ab conjugated to the NG and distribution in the body after intravenous (IV injection have been quantitatively analyzed using a tracer isotope-labeled [125I]IgG. As a proof of concept, Ab-NG are loaded with dexamethasone, an anti-inflammatory therapeutic, and the drug uptake and release kinetics are measured by HPLC. In vivo studies in mice showed that: i ICAM-NG accumulates in mouse lungs (∼120% ID/g vs ∼15% ID/g of IgG-NG; and, ii DEX encapsulated in ICAM-NG, but not in IgG-NG practically blocks LPS-induced overexpression of pro-inflammatory cell adhesion molecules including ICAM-1 in the pulmonary inflammation.

  16. TNF suppresses acute intestinal inflammation by inducing local glucocorticoid synthesis

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    Noti, Mario; Corazza, Nadia; Mueller, Christoph; Berger, Barbara

    2010-01-01

    Although tumor necrosis factor (α) (TNF) exerts proinflammatory activities in a variety of diseases, including inflammatory bowel disease, there is increasing evidence for antiinflammatory actions of TNF. In contrast, glucocorticoids (GCs) are steroid hormones that suppress inflammation, at least in part by regulating the expression and action of TNF. We report that TNF induces extraadrenal production of immunoregulatory GCs in the intestinal mucosa during acute intestinal inflammation. The absence of TNF results in a lack of colonic GC synthesis and exacerbation of dextran sodium sulfate–induced colitis. TNF seems to promote local steroidogenesis by directly inducing steroidogenic enzymes in intestinal epithelial cells. Therapeutic administration of TNF induces GC synthesis in oxazolone-induced colitis and ameliorates intestinal inflammation, whereas inhibition of intestinal GC synthesis abrogates the therapeutic effect of TNF. These data show that TNF suppresses the pathogenesis of acute intestinal inflammation by promoting local steroidogenesis. PMID:20439544

  17. Multifunctions of dietary polyphenols in the regulation of intestinal inflammation

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    Makoto Shimizu

    2017-01-01

    Full Text Available Food for specified health use is a type of functional food approved by the Japanese government, with more than 1250 products in 10 health-claim categories being approved as of April 2016. Polyphenols are currently used as functional ingredients in seven of the 10 categories. Although they have not yet been used for the food-for-specified-health-use category of “gut health promotion,” polyphenols are expected to contribute to the future development of gut-modulating food. Intestinal functions include digestion/absorption, acting as a barrier, recognition of external factors, and signal transduction. Owing to incessant exposure to external stress factors including food substances, bacteria, and environmental chemicals, intestines are always inflammatory to some extent, which may cause damage to and dysfunction of intestinal tissues depending on the situation. We identified food factors that could suppress immoderate inflammation in the intestines. In addition to certain amino acids and peptides, polyphenols such as chlorogenic acid and isoflavones were found to suppress inflammation in intestinal cells. Intestinal inflammation is caused by various factors in diverse mechanisms. Recent studies revealed that activation of pattern recognition receptors, such as Toll-like receptors and nucleotide-binding oligomerization domain proteins, in epithelial cells triggers intestinal inflammation. Intracellular receptors or signaling molecules controlling the intestinal detoxification system are also involved in the regulation of inflammation. Differentiation of regulatory T cells by activating a transcription factor Foxp-3 is known to suppress intestinal inflammation. A variety of phytochemicals including polyphenols modulate these receptors and signaling molecules, and are thus anti-inflammatory. Polyphenols affect epigenetic changes occurring in intestinal tissues by interacting with the enzymes responsible for DNA methylation and histone acetylation

  18. Melatonin reduces changes to small intestinal microvasculature during systemic inflammation.

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    Lansink, Maren Oude; Patyk, Vivien; de Groot, Herbert; Effenberger-Neidnicht, Katharina

    2017-05-01

    Systemic inflammation is known to impair the microcirculation in intestine and other organs as a result of multifactorial events. Here, we show that melatonin selectively reduces changes to the small intestinal microvasculature during systemic inflammation. Lipopolysaccharide (LPS) was infused at a rate of 0.5 mg/kg × h to induce systemic inflammation in male Wistar rats. Melatonin (single dose: 3 mg/kg × 15 min) was intravenously administered before as well as 120 and 240 min after the beginning of the LPS infusion. Systemic parameters were determined in regular intervals. Small intestine, liver, and kidney were histologically (structure of the microvessels, intravascular blood accumulation, and hemorrhages) and immunohistochemically (mast cells, granulocytes, and macrophages) analyzed. Continuous infusion of LPS resulted in dilated microvessels with intravascular blood accumulation (congestion) in liver and small intestine, the latter being particularly pronounced. Blood vessel walls remained intact, there were no hemorrhages. Melatonin significantly reduced these changes to the microvasculature in small intestine, but not in liver. It further reduced mast cell and granulocytes count in small intestine enhanced by LPS. However, except for the systemic blood pressure, melatonin neither improved LPS-dependent changes to systemic parameters nor mortality. Changes to the microvasculature during systemic inflammation are most pronounced in small intestine. Melatonin selectively diminishes these changes to small intestinal microvasculature, probably by reducing the local immune cells recruitment. However, changes to the small intestine are not decisive for the survival. We assume that the therapeutic benefit of melatonin is more likely in local intestinal inflammation. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Functions and Signaling Pathways of Amino Acids in Intestinal Inflammation

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    Fang He

    2018-01-01

    Full Text Available Intestine is always exposed to external environment and intestinal microorganism; thus it is more sensitive to dysfunction and dysbiosis, leading to intestinal inflammation, such as inflammatory bowel disease (IBD, irritable bowel syndrome (IBS, and diarrhea. An increasing number of studies indicate that dietary amino acids play significant roles in preventing and treating intestinal inflammation. The review aims to summarize the functions and signaling mechanisms of amino acids in intestinal inflammation. Amino acids, including essential amino acids (EAAs, conditionally essential amino acids (CEAAs, and nonessential amino acids (NEAAs, improve the functions of intestinal barrier and expressions of anti-inflammatory cytokines and tight junction proteins but decrease oxidative stress and the apoptosis of enterocytes as well as the expressions of proinflammatory cytokines in the intestinal inflammation. The functions of amino acids are associated with various signaling pathways, including mechanistic target of rapamycin (mTOR, inducible nitric oxide synthase (iNOS, calcium-sensing receptor (CaSR, nuclear factor-kappa-B (NF-κB, mitogen-activated protein kinase (MAPK, nuclear erythroid-related factor 2 (Nrf2, general controlled nonrepressed kinase 2 (GCN2, and angiotensin-converting enzyme 2 (ACE2.

  20. Fecal markers of intestinal inflammation and intestinal permeability are elevated in Parkinson's disease.

    Science.gov (United States)

    Schwiertz, Andreas; Spiegel, Jörg; Dillmann, Ulrich; Grundmann, David; Bürmann, Jan; Faßbender, Klaus; Schäfer, Karl-Herbert; Unger, Marcus M

    2018-02-12

    Intestinal inflammation and increased intestinal permeability (both possibly fueled by dysbiosis) have been suggested to be implicated in the multifactorial pathogenesis of Parkinson's disease (PD). The objective of the current study was to investigate whether fecal markers of inflammation and impaired intestinal barrier function corroborate this pathogenic aspect of PD. In a case-control study, we quantitatively analyzed established fecal markers of intestinal inflammation (calprotectin and lactoferrin) and fecal markers of intestinal permeability (alpha-1-antitrypsin and zonulin) in PD patients (n = 34) and controls (n = 28, group-matched for age) by enzyme-linked immunosorbent assay. The study design controlled for potential confounding factors. Calprotectin, a fecal marker of intestinal inflammation, and two fecal markers of increased intestinal permeability (alpha-1-antitrypsin and zonulin) were significantly elevated in PD patients compared to age-matched controls. Lactoferrin, as a second fecal marker of intestinal inflammation, showed a non-significant trend towards elevated concentrations in PD patients. None of the four fecal markers correlated with disease severity, PD subtype, dopaminergic therapy, or presence of constipation. Fecal markers reflecting intestinal inflammation and increased intestinal permeability have been primarily investigated in inflammatory bowel disease so far. Our data indicate that calprotectin, alpha-1-antitrypsin and zonulin could be useful non-invasive markers in PD as well. Even though these markers are not disease-specific, they corroborate the hypothesis of an intestinal inflammation as contributing factor in the pathogenesis of PD. Further investigations are needed to determine whether calprotectin, alpha-1-antitrypsin and zonulin can be used to define PD subgroups and to monitor the effect of interventions in PD. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. The role of CDX2 in intestinal homeostasis and inflammation

    DEFF Research Database (Denmark)

    Coskun, Mehmet; Troelsen, Jesper Thorvald; Nielsen, Ole Haagen

    2011-01-01

    a causal role in a large number of diseases and developmental disorders. Inflammatory bowel disease (IBD) is characterized by a chronically inflamed mucosa caused by dysregulation of the intestinal immune homeostasis. The aetiology of IBD is thought to be a combination of genetic and environmental factors......, including luminal bacteria. The Caudal-related homeobox transcription factor 2 (CDX2) is critical in early intestinal differentiation and has been implicated as a master regulator of the intestinal homeostasis and permeability in adults. When expressed, CDX2 modulates a diverse set of processes including...... of the intestinal homeostasis and further to reveal its potential role in inflammation....

  2. Polyopes affinis alleviates airway inflammation in a murine model of ...

    Indian Academy of Sciences (India)

    Marine algae have been utilized in food as well as medicine products for a variety of purposes. The purpose of this study was to determine whether an ethanol extract of Polyopes affinis (P.affinis) can inhibit the pathogenesis of T helper 2 (Th2)-mediated allergen-induced airway inflammation in a murine model of asthma.

  3. Intestinal Epithelial Sirtuin 1 Regulates Intestinal Inflammation During Aging in Mice by Altering the Intestinal Microbiota.

    Science.gov (United States)

    Wellman, Alicia S; Metukuri, Mallikarjuna R; Kazgan, Nevzat; Xu, Xiaojiang; Xu, Qing; Ren, Natalie S X; Czopik, Agnieszka; Shanahan, Michael T; Kang, Ashley; Chen, Willa; Azcarate-Peril, M Andrea; Gulati, Ajay S; Fargo, David C; Guarente, Leonard; Li, Xiaoling

    2017-09-01

    Intestinal epithelial homeostasis is maintained by complex interactions among epithelial cells, commensal gut microorganisms, and immune cells. Disruption of this homeostasis is associated with disorders such as inflammatory bowel disease (IBD), but the mechanisms of this process are not clear. We investigated how Sirtuin 1 (SIRT1), a conserved mammalian NAD + -dependent protein deacetylase, senses environmental stress to alter intestinal integrity. We performed studies of mice with disruption of Sirt1 specifically in the intestinal epithelium (SIRT1 iKO, villin-Cre+, Sirt1 flox/flox mice) and control mice (villin-Cre-, Sirt1 flox/flox ) on a C57BL/6 background. Acute colitis was induced in some mice by addition of 2.5% dextran sodium sulfate to drinking water for 5-9 consecutive days. Some mice were given antibiotics via their drinking water for 4 weeks to deplete their microbiota. Some mice were fed with a cholestyramine-containing diet for 7 days to sequester their bile acids. Feces were collected and proportions of microbiota were analyzed by 16S rRNA amplicon sequencing and quantitative PCR. Intestines were collected from mice and gene expression profiles were compared by microarray and quantitative PCR analyses. We compared levels of specific mRNAs between colon tissues from age-matched patients with ulcerative colitis (n=10) vs without IBD (n=8, controls). Mice with intestinal deletion of SIRT1 (SIRT1 iKO) had abnormal activation of Paneth cells starting at the age of 5-8 months, with increased activation of NF-κB, stress pathways, and spontaneous inflammation at 22-24 months of age, compared with control mice. SIRT1 iKO mice also had altered fecal microbiota starting at 4-6 months of age compared with control mice, in part because of altered bile acid metabolism. Moreover, SIRT1 iKO mice with defective gut microbiota developed more severe colitis than control mice. Intestinal tissues from patients with ulcerative colitis expressed significantly lower

  4. Genetic Factors in Animal Models of Intestinal Inflammation

    Directory of Open Access Journals (Sweden)

    R Balfour Sartor

    1995-01-01

    Full Text Available The critical importance of host genetic susceptibility in determining chronicity, aggressiveness and complications of intestinal inflammation is clearly demonstrated by studies of inbred rodents, transgenic rats and spontaneous mutants. Inbred Lewis rats challenged by purified bacterial cell wall polymers, indomethacin or small bowel bacterial overgrowth develop chronic granulomatous intestinal inflammation with fibrosis and extraintestinal manifestations, whereas Fischer (major histocompatibility complex identical to Lewis and Buffalo rats identically stimulated demonstrate only self-limited enterocolitis with no chronic inflammation, fibrosis, granulomas or extraintestinal inflammation. Similar differential patterns of intestinal inflammation are apparent in inbred mouse strains challenged with trinitrobenzene-sulphonic acid, Citrobacter freundii or backcrossed with T cell receptor deficient (knockout mice. The dominant role of genetic background in induction of intestinal inflammation is further documented by spontaneous colitis which develops in spontaneously mutant mice, cotton-top tamarins, human leukocyte antigen-B27/ β2 microglobulin transgenic rats and mice with targeted deletions of certain immunoregulatory cytokine and T lymphocyte genes. Identification of the immunological mechanisms of host genetic susceptibility and the genetic basis of spontaneous colitis should provide new insights into the pathogenesis of human inflammatory bowel disease.

  5. Inflammasome in Intestinal Inflammation and Cancer

    Directory of Open Access Journals (Sweden)

    Tiago Nunes

    2013-01-01

    Full Text Available The activation of specific cytosolic pathogen recognition receptors, the nucleotide-binding-oligomerization-domain- (NOD- like receptors (NLRs, leads to the assembly of the inflammasome, a multimeric complex platform that activates caspase-1. The caspase-1 pathway leads to the upregulation of important cytokines from the interleukin (IL-1 family, IL-1β, and IL-18, with subsequent activation of the innate immune response. In this review, we discuss the molecular structure, the mechanisms behind the inflammasome activation, and its possible role in the pathogenesis of inflammatory bowel diseases and intestinal cancer. Here, we show that the available data points towards the importance of the inflammasome in the innate intestinal immune response, being the complex involved in the maintenance of intestinal homeostasis, correct intestinal barrier function and efficient elimination of invading pathogens.

  6. Determination of Intestine Inflammation Markers in Diagnostic Search in Children with Intestinal Diseases

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    N.V. Pavlenko

    2016-08-01

    Full Text Available Introduction. Prevalence of bowel diseases in children is the second, trailing only the diseases of gastroduodenal zone and growing in recent years. Actual one is the problem of differential diagnosis of functional and inflammatory intestinal diseases using non-invasive methods on the prehospital stage and as a screening. Objective. Comparative analysis of fecal markers of the bowel inflammation (lactoferrine and calprotectine with endoscopy and morphology of intestinal mucosa in children. Matherials and methods. 49 children aged 6–18 years were examined. All patients underwent endoscopic and morphological study of the intestine, coprotest, determination of fecal markers of bowel inflammation (lactoferrin and calprotectine. Results. It is shown that in young children, the intestinal mucosa mainly hadn’t endoscopic changes, coprotest and morphological examination didn’t reveal the signs of inflammation, fecal intestinal inflammation markers were negative (p < 0.05. In the group of older children, moderate or marked catarrhal changes were found endoscopically, coprotest results were typical of inflammation in the intestines, it was morphologically proved the presence of chronic inflammation of the mucous membrane of the colon with signs of atrophy, the results of lactoferrin and calprotectine determination were positive (p < 0.05. Conclusion. The findings suggest that the evaluation of calprotectine and lactoferrin can be used in pediatric patients because of its non-invasiveness as diagnostic screening for the selection of patients for the further endoscopic examination and diagnostic search.

  7. Epithelial Cell Inflammasomes in Intestinal Immunity and Inflammation

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    Andrea C. Lei-Leston

    2017-09-01

    Full Text Available Pattern recognition receptors (PRR, such as NOD-like receptors (NLRs, sense conserved microbial signatures, and host danger signals leading to the coordination of appropriate immune responses. Upon activation, a subset of NLR initiate the assembly of a multimeric protein complex known as the inflammasome, which processes pro-inflammatory cytokines and mediates a specialized form of cell death known as pyroptosis. The identification of inflammasome-associated genes as inflammatory bowel disease susceptibility genes implicates a role for the inflammasome in intestinal inflammation. Despite the fact that the functional importance of inflammasomes within immune cells has been well established, the contribution of inflammasome expression in non-hematopoietic cells remains comparatively understudied. Given that intestinal epithelial cells (IEC act as a barrier between the host and the intestinal microbiota, inflammasome expression by these cells is likely important for intestinal immune homeostasis. Accumulating evidence suggests that the inflammasome plays a key role in shaping epithelial responses at the host–lumen interface with many inflammasome components highly expressed by IEC. Recent studies have exposed functional roles of IEC inflammasomes in mucosal immune defense, inflammation, and tumorigenesis. In this review, we present the main features of the predominant inflammasomes and their effector mechanisms contributing to intestinal homeostasis and inflammation. We also discuss existing controversies in the field and open questions related to their implications in disease. A comprehensive understanding of the molecular basis of intestinal inflammasome signaling could hold therapeutic potential for clinical translation.

  8. Zinc treatment ameliorates diarrhea and intestinal inflammation in undernourished rats

    OpenAIRE

    de Queiroz, Camila AA; Fonseca, Said Gonçalves C; Frota, Priscila B; Figueiredo, Ítalo L; Aragão, Karoline S; Magalhães, Carlos Emanuel C; de Carvalho, Cibele BM; Lima, Aldo Ângelo M; Ribeiro, Ronaldo A; Guerrant, Richard L; Moore, Sean R; Oriá, Reinaldo B

    2014-01-01

    Background WHO guidelines recommend zinc supplementation as a key adjunct therapy for childhood diarrhea in developing countries, however zinc’s anti-diarrheal effects remain only partially understood. Recently, it has been recognized that low-grade inflammation may influence stunting. In this study, we examined whether oral zinc supplementation could improve weight, intestinal inflammation, and diarrhea in undernourished weanling rats. Methods Rats were undernourished using a northeastern Br...

  9. Neonatal exposure to fecal antigens reduces intestinal inflammation.

    Science.gov (United States)

    Sydora, Beate C; McFarlane, Sarah M; Doyle, Jason S G; Fedorak, Richard N

    2011-04-01

    A role for bacterial antigens in the pathogenesis of inflammatory bowel disease (IBD) has been established in enhanced humoral and cellular immune response to ubiquitous antigens of the enteric flora. However, we have recently shown that bacterial antigens in the absence of live bacteria cannot initiate an intestinal inflammation in IBD-prone interleukin (IL)-10 gene-deficient mice. The objective was to investigate whether neonatal exposure to antigens of their own endogenous flora can tolerize mice to bacterial antigens. IL-10 gene-deficient neonates were injected intraperitoneally within 72 hours of birth with a sterile solution of bacterial lysates prepared from fecal material of either conventionally raised mice (contains bacterial antigens) or axenic mice (lacks bacterial antigens). The onset of intestinal inflammation was monitored as the appearance of occult blood in the stool in weekly hemoccult analysis. Mice were sacrificed between age 15 and 19 weeks and tested for histopathologic injury, intestinal inflammation, and systemic response to bacterial antigens. In mice neonatally exposed to bacterial antigens the onset of intestinal inflammation was delayed and the incidence of histopathologic injury at age 18 weeks was reduced. In addition, mice injected with lysates from conventionally raised mice exhibited decreased release of proinflammatory cytokines (interferon gamma [IFN-γ] and IL-17) in intestinal tissue and demonstrated reduced bacteria-stimulated systemic responses when compared to mice injected with lysates derived from bacteria-free, axenic mice. Neonatal intraperitoneal injection of antigens from the commensal flora causes long-lasting changes in systemic and mucosal immune responses resulting in delayed onset of intestinal inflammation and injury in IBD-prone IL-10 gene-deficient mice. Copyright © 2010 Crohn's & Colitis Foundation of America, Inc.

  10. The role of PGE2 in intestinal inflammation and tumorigenesis.

    Science.gov (United States)

    Montrose, David C; Nakanishi, Masako; Murphy, Robert C; Zarini, Simona; McAleer, Jeremy P; Vella, Anthony T; Rosenberg, Daniel W

    2015-01-01

    Release of the free fatty acid arachidonic acid (AA) by cytoplasmic phospholipase A2 (cPLA2) and its subsequent metabolism by the cyclooxygenase and lipoxygenase enzymes produces a broad panel of eicosanoids including prostaglandins (PGs). This study sought to investigate the roles of these mediators in experimental models of inflammation and inflammation-associated intestinal tumorigenesis. Using the dextran sodium sulfate (DSS) model of experimental colitis, we first investigated how a global reduction in eicosanoid production would impact intestinal injury by utilizing cPLA2 knockout mice. cPLA2 deletion enhanced colonic injury, reflected by increased mucosal ulceration and pro-inflammatory cytokine expression. Increased disease severity was associated with a significant reduction in the levels of several eicosanoid metabolites, including PGE2. We further assessed the precise role of PGE2 synthesis on mucosal injury and repair by utilizing mice with a genetic deletion of microsomal PGE synthase-1 (mPGES-1), the terminal synthase in the formation of inducible PGE2. DSS exposure caused more extensive acute injury as well as impaired recovery in knockout mice compared to wild-type littermates. Increased intestinal damage was associated with both reduced PGE2 levels as well as altered levels of other eicosanoids including PGD2. To determine whether this metabolic redirection impacted inflammation-associated intestinal tumorigenesis, Apc(Min/+) and Apc(Min/+):mPGES-1(-/-) mice were exposed to DSS. DSS administration caused a reduction in the number of intestinal polyps only in Apc(Min/+):mPGES-1(-/-) mice. These results demonstrate the importance of the balance of prostaglandins produced in the intestinal tract for maintaining intestinal homeostasis and impacting tumor development. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Cannabidiol reduces intestinal inflammation through the control of neuroimmune axis.

    Directory of Open Access Journals (Sweden)

    Daniele De Filippis

    Full Text Available Enteric glial cells (EGC actively mediate acute and chronic inflammation in the gut; EGC proliferate and release neurotrophins, growth factors, and pro-inflammatory cytokines which, in turn, may amplify the immune response, representing a very important link between the nervous and immune systems in the intestine. Cannabidiol (CBD is an interesting compound because of its ability to control reactive gliosis in the CNS, without any unwanted psychotropic effects. Therefore the rationale of our study was to investigate the effect of CBD on intestinal biopsies from patients with ulcerative colitis (UC and from intestinal segments of mice with LPS-induced intestinal inflammation. CBD markedly counteracted reactive enteric gliosis in LPS-mice trough the massive reduction of astroglial signalling neurotrophin S100B. Histological, biochemical and immunohistochemical data demonstrated that S100B decrease was associated with a considerable decrease in mast cell and macrophages in the intestine of LPS-treated mice after CBD treatment. Moreover the treatment of LPS-mice with CBD reduced TNF-α expression and the presence of cleaved caspase-3. Similar results were obtained in ex vivo cultured human derived colonic biopsies. In biopsies of UC patients, both during active inflammation and in remission stimulated with LPS+INF-γ, an increased glial cell activation and intestinal damage were evidenced. CBD reduced the expression of S100B and iNOS proteins in the human biopsies confirming its well documented effect in septic mice. The activity of CBD is, at least partly, mediated via the selective PPAR-gamma receptor pathway. CBD targets enteric reactive gliosis, counteracts the inflammatory environment induced by LPS in mice and in human colonic cultures derived from UC patients. These actions lead to a reduction of intestinal damage mediated by PPARgamma receptor pathway. Our results therefore indicate that CBD indeed unravels a new therapeutic strategy to

  12. The octapetide NAP alleviates intestinal and extra-intestinal anti-inflammatory sequelae of acute experimental colitis.

    Science.gov (United States)

    Heimesaat, Markus M; Giladi, Eliezer; Kühl, Anja A; Bereswill, Stefan; Gozes, Illana

    2018-03-01

    The octapeptide NAP has been shown to exert neuroprotective properties and reduce neuro-inflammatory responses. The aim of the present study was to investigate if NAP provides anti-inflammatory effects in acute murine colitis. To address this, C57BL/6 j mice were challenged with 3.5% dextran sulfate sodium from day 0 until day 6 to induce colitis, either treated intraperitoneally with NAP or placebo (NaCl 0.9%) from day 1 until day 6 post-induction (p.i.) and subjected to in depth macroscopic, microscopic and immunological evaluations. Whereas NAP application did not alleviate macroscopic (i.e. clinical) sequelae of colitis, lower numbers of apoptotic, but higher counts of proliferating/regenerating colonic epithelial cells could be observed in NAP as compared to placebo treated mice at day 7 p.i. Furthermore, lower numbers of adaptive immune cells such as T lymphocytes and regulatory T cells were abundant in the colonic mucosa and lamina propria upon NAP versus placebo treatment that were accompanied by less colonic secretion of pro-inflammatory mediators including IFN-γ and nitric oxide at day 7 p.i. In mesenteric lymph nodes, pro-inflammatory IFN-γ, TNF and IL-6 concentrations were increased in placebo, but not NAP treated mice at day 7 p.i., whereas interestingly, elevated anti-inflammatory IL-10 levels could be observed in NAP treated mice only. The assessed anti-inflammatory properties of NAP were not restricted to the intestinal tract, given that in extra-intestinal compartments such as the kidneys, IFN-γ levels increased in placebo, but not NAP treated mice upon colitis induction. NAP induced effects were accompanied by distinct changes in intestinal microbiota composition, given that colonic luminal loads of bifidobacteria, regarded as anti-inflammatory, "health-promoting" commensal species, were two orders of magnitude higher in NAP as compared to placebo treated mice and even naive controls. In conclusion, NAP alleviates intestinal and extra-intestinal

  13. Antagonist of GH-releasing hormone receptors alleviates experimental ocular inflammation.

    Science.gov (United States)

    Qin, Yong Jie; Chan, Sun On; Chong, Kelvin Kam Lung; Li, Benjamin Fuk Loi; Ng, Tsz Kin; Yip, Yolanda Wong Ying; Chen, Haoyu; Zhang, Mingzhi; Block, Norman L; Cheung, Herman S; Schally, Andrew V; Pang, Chi Pui

    2014-12-23

    Disruptions in immunity and occurrence of inflammation cause many eye diseases. The growth hormone-releasing hormone-growth hormone-insulin-like growth factor-1 (GHRH-GH-IGF1) axis exerts regulatory effects on the immune system. Its involvement in ocular inflammation remains to be investigated. Here we studied this signaling in endotoxin-induced uveitis (EIU) generated by LPS. The increase in GHRH receptor (GHRH-R) protein levels was parallel to the increase in mRNA levels of pituitary-specific transcription factor-1, GHRH-R splice variant 1, GHRH, and GH following LPS insult. Elevation of GHRH-R and GH receptor was localized on the epithelium of the iris and ciliary body, and GHRH-R was confined to the infiltrating macrophages and leukocytes in aqueous humor but not to those in stroma. Treatment with GHRH-R antagonist decreased LPS-stimulated surges of GH and IGF1 in aqueous humor and alleviated inflammation by reducing the infiltration of macrophages and leukocytes and the production of TNF-α, IL-1β, and monocyte chemotactic protein-1. Our results indicate that inflammation in the iris and ciliary body involves the activation of GHRH signaling, which affects the recruitment of immune cells and the production of proinflammatory mediators that contribute to EIU pathogenesis. Moreover, the results suggest that GHRH-R antagonists are potential therapeutic agents for the treatment of acute ocular inflammation.

  14. Homing of immune cells: role in homeostasis and intestinal inflammation.

    Science.gov (United States)

    Hart, Ailsa L; Ng, Siew C; Mann, Elizabeth; Al-Hassi, Hafid Omar; Bernardo, David; Knight, Stella C

    2010-11-01

    Rather like a satellite navigation system directing a vehicle to a particular destination defined by post-code, immune cells have homing molecules or "immune post-codes" enabling them to be recruited to specific organs, such as the intestine or skin. An efficient system would be designed such that the site of entry of an antigen influences the homing of effector T cells back to the appropriate organ. For example, to mount an immune response against an intestinal pathogen, T cells with a propensity to home to the gut to clear the infection would be induced. In health, there is such a sophisticated and finely tuned system in operation, enabling an appropriate balance of immune activity in different anatomical compartments. In disease states such as inflammatory bowel disease (IBD), which is characterized by intestinal inflammation and often an inflammatory process involving other organs such as skin, joints, liver, and eye, there is accumulating evidence that there is malfunction of this immune cell trafficking system. The clinical importance of dysregulated immune cell trafficking in IBD is reflected in recently proven efficacious therapies that target trafficking pathways such as natalizumab, an α4 integrin antibody, and Traficet-EN, a chemokine receptor-9 (CCR9) antagonist. Here we review the mechanisms involved in the homing of immune cells to different tissues, in particular the intestine, and focus on alterations in immune cell homing pathways in IBD. Unraveling the mechanisms underlying the immune post-code system would assist in achieving the goal of tissue-specific immunotherapy.

  15. Human intestinal microbiota composition is associated with local and systemic inflammation in obesity

    NARCIS (Netherlands)

    Verdam, F.J.; Fuentes Enriquez de Salamanca, S.; Jonge, de C.; Zoetendal, E.G.; Erbil, R.; Greve, J.W.; Buurman, W.A.; Vos, de W.M.; Rensen, S.S.

    2013-01-01

    OBJECTIVE: Intestinal microbiota have been suggested to contribute to the development of obesity, but the mechanism remains elusive. The relationship between microbiota composition, intestinal permeability, and inflammation in nonobese and obese subjects was investigated. DESIGN AND METHODS: Fecal

  16. Ganoderma tsugae supplementation alleviates bronchoalveolar inflammation in an airway sensitization and challenge mouse model.

    Science.gov (United States)

    Lin, Jin-Yuarn; Chen, Miaw-Ling; Chiang, Bor-Luen; Lin, Bi-Fong

    2006-02-01

    Ganoderma tsugae (a Chinese mushroom Songshan lingzhi) cultivated in Taiwan is extensively used in Chinese traditional medicine to treat different diseases. To determine whether G. tsugae has anti-inflammatory effects on bronchoalveolar inflammation in vivo, we investigated the anti-inflammatory effects of G. tsugae products, YK01 and YK07, on bronchoalveolar inflammation using an airway sensitization and challenge mouse model. Female BALB/c mice were weekly sensitized by intraperitoneal injection of ovalbumin (OVA) three times and challenged with aerosolized OVA twice. Differential cell counts of infiltrating leukocytes, inflammatory mediators, cytokines in bronchoalvelor lavage fluid (BALF) of OVA-challenged mice were examined after continuously consuming G. tsugae diets for 5 weeks. We found that supplementation of G. tsugae significantly decreased total infiltrating leukocytes and lymphocyte percentage in BALF in the experimental groups. Supplementation of G. tsugae also significantly reduced inflammatory mediators in BALF including histamine, prostaglandin E2, eotaxin, and protein levels, however the levels of pro-inflammatory cytokines, interleukin (IL)-1beta and IL-6, in BALF did not significantly change. These results suggest that both G. tsugae supplementation diets YK01 and YK07 might alleviate bronchoalveolar inflammation via decreasing the infiltration of inflammatory cells and the secretion of inflammatory mediators into the local tissues of lungs and airways. Further, these results indicate that the relief of bronchoalveolar inflammation in an airway sensitization murine model provides a possible therapeutic application for G. tsugae in allergic asthma.

  17. Intestinal parasitic infections amongst Orang Asli (indigenous) in Malaysia: has socioeconomic development alleviated the problem?

    Science.gov (United States)

    Lim, Y A L; Romano, N; Colin, N; Chow, S C; Smith, H V

    2009-08-01

    ensure the whole mechanism of delivery and empowerment by the government agencies become more efficient and productive in alleviating intestinal parasitic infections in these communities.

  18. Ambient carbon monoxide associated with alleviated respiratory inflammation in healthy young adults

    International Nuclear Information System (INIS)

    Zhao, Zhuohui; Chen, Renjie; Lin, Zhijing; Cai, Jing; Yang, Yingying; Yang, Dandan; Norback, Dan; Kan, Haidong

    2016-01-01

    There is increasing controversy on whether acute exposure to ambient carbon monoxide (CO) is hazardous on respiratory health. We therefore performed a longitudinal panel study to evaluate the acute effects of ambient CO on fractional exhaled nitric oxide (FeNO), a well-established biomarker of airway inflammation. We completed 4–6 rounds of health examinations among 75 healthy young adults during April to June in 2013 in Shanghai, China. We applied the linear mixed-effect model to investigate the short-term associations between CO and FeNO. CO exposure during 2–72 h preceding health tests was significantly associated with decreased FeNO levels. For example, an interquartile range increase (0.3 mg/m 3 ) of 2-h CO exposure corresponded to 10.6% decrease in FeNO. This association remained when controlling for the concomitant exposure to co-pollutants. This study provided support that short-term exposure to ambient CO might be related with reduced levels of FeNO, a biomarker of lower airway inflammation. - Highlights: • We completed 4–6 rounds of health examinations among 75 healthy young adults. • Short-term CO exposure was significantly associated with decreased FeNO levels. • The inverse association between CO and FeNO was robust controlling for co-pollutants. - Short-term exposure to ambient carbon monoxide may alleviate the respiratory inflammation.

  19. Glucocorticoids alleviate intestinal ER stress by enhancing protein folding and degradation of misfolded proteins

    Science.gov (United States)

    Das, Indrajit; Png, Chin Wen; Oancea, Iulia; Hasnain, Sumaira Z.; Lourie, Rohan; Proctor, Martina; Eri, Rajaraman D.; Sheng, Yong; Crane, Denis I.; Florin, Timothy H.

    2013-01-01

    Endoplasmic reticulum (ER) stress in intestinal secretory cells has been linked with colitis in mice and inflammatory bowel disease (IBD). Endogenous intestinal glucocorticoids are important for homeostasis and glucocorticoid drugs are efficacious in IBD. In Winnie mice with intestinal ER stress caused by misfolding of the Muc2 mucin, the glucocorticoid dexamethasone (DEX) suppressed ER stress and activation of the unfolded protein response (UPR), substantially restoring goblet cell Muc2 production. In mice lacking inflammation, a glucocorticoid receptor antagonist increased ER stress, and DEX suppressed ER stress induced by the N-glycosylation inhibitor, tunicamycin (Tm). In cultured human intestinal secretory cells, in a glucocorticoid receptor-dependent manner, DEX suppressed ER stress and UPR activation induced by blocking N-glycosylation, reducing ER Ca2+ or depleting glucose. DEX up-regulated genes encoding chaperones and elements of ER-associated degradation (ERAD), including EDEM1. Silencing EDEM1 partially inhibited DEX’s suppression of misfolding-induced ER stress, showing that DEX enhances ERAD. DEX inhibited Tm-induced MUC2 precursor accumulation, promoted production of mature mucin, and restored ER exit and secretion of Winnie mutant recombinant Muc2 domains, consistent with enhanced protein folding. In IBD, glucocorticoids are likely to ameliorate ER stress by promoting correct folding of secreted proteins and enhancing removal of misfolded proteins from the ER. PMID:23650437

  20. Microbiota-Mediated Inflammation and Antimicrobial Defense in the Intestine

    Science.gov (United States)

    Caballero, Silvia; Pamer, Eric G.

    2015-01-01

    The diverse microbial populations constituting the intestinal microbiota promote immune development and differentiation, but because of their complex metabolic requirements and the consequent difficulty culturing them, they remained, until recently, largely uncharacterized and mysterious. In the last decade, deep nucleic acid sequencing platforms, new computational and bioinformatics tools, and full-genome characterization of several hundred commensal bacterial species facilitated studies of the microbiota and revealed that differences in microbiota composition can be associated with inflammatory, metabolic, and infectious diseases, that each human is colonized by a distinct bacterial flora, and that the microbiota can be manipulated to reduce and even cure some diseases. Different bacterial species induce distinct immune cell populations that can play pro- and anti-inflammatory roles, and thus the composition of the microbiota determines, in part, the level of resistance to infection and susceptibility to inflammatory diseases. This review summarizes recent work characterizing commensal microbes that contribute to the antimicrobial defense/inflammation axis. PMID:25581310

  1. Exercise alleviates depression related systemic inflammation in chronic obstructive pulmonary disease patients.

    Science.gov (United States)

    Abd El-Kader, Shehab M; Al-Jiffri, Osama H

    2016-12-01

    Depression is a highly prevalent co-morbidity in Chronic Obstructive Pulmonary Disease (COPD) which was shown to be associated with a worse course of disease, including reduced quality of life and increased symptoms burden, healthcare use, and even mortality. It has been speculated that systemic inflammation may play a role in the presence of depression. Currently, physical activity is an important lifestyle factor that has the potential to modify inflammatory cytokines and depression, however our understanding of how to use exercise effectively in COPD patients to alleviate depression related systemic inflammation is incomplete and has prompted our interest to identify the type and intensities of effective exercise. The aim of this study was to measure the changes in depression related systemic inflammation of aerobic exercise training in COPD patients in Jeddah area. Eighty patients with moderate severity of COPD participated in this study and were divided into two groups; the first group received aerobic exercise, whereas the second group received no exercise training for 12 weeks. The mean values of tumor necrosis factor-alpha (TNF-α), interleukin-4 (IL-4), interleukin-6 (IL-6), C-reactive protein (CRP) and Beck Depression Inventory (BDI) scores were significantly decreased in in group (A) after treatments, but the changes in group (B) were not significant .Also, there were significant differences between mean levels of the investigated parameters in group (A) and group (B) at the end of the study. Aerobic exercise is an effective treatment policy to improve depression related to systemic inflammation in patients with chronic obstructive pulmonary disease.

  2. Salmonella uses energy taxis to benefit from intestinal inflammation.

    Science.gov (United States)

    Rivera-Chávez, Fabian; Winter, Sebastian E; Lopez, Christopher A; Xavier, Mariana N; Winter, Maria G; Nuccio, Sean-Paul; Russell, Joseph M; Laughlin, Richard C; Lawhon, Sara D; Sterzenbach, Torsten; Bevins, Charles L; Tsolis, Renée M; Harshey, Rasika; Adams, L Garry; Bäumler, Andreas J

    2013-01-01

    Chemotaxis enhances the fitness of Salmonella enterica serotype Typhimurium (S. Typhimurium) during colitis. However, the chemotaxis receptors conferring this fitness advantage and their cognate signals generated during inflammation remain unknown. Here we identify respiratory electron acceptors that are generated in the intestinal lumen as by-products of the host inflammatory response as in vivo signals for methyl-accepting chemotaxis proteins (MCPs). Three MCPs, including Trg, Tsr and Aer, enhanced the fitness of S. Typhimurium in a mouse colitis model. Aer mediated chemotaxis towards electron acceptors (energy taxis) in vitro and required tetrathionate respiration to confer a fitness advantage in vivo. Tsr mediated energy taxis towards nitrate but not towards tetrathionate in vitro and required nitrate respiration to confer a fitness advantage in vivo. These data suggest that the energy taxis receptors Tsr and Aer respond to distinct in vivo signals to confer a fitness advantage upon S. Typhimurium during inflammation by enabling this facultative anaerobic pathogen to seek out favorable spatial niches containing host-derived electron acceptors that boost its luminal growth.

  3. Zinc treatment ameliorates diarrhea and intestinal inflammation in undernourished rats.

    Science.gov (United States)

    de Queiroz, Camila A A; Fonseca, Said Gonçalves C; Frota, Priscila B; Figueiredo, Italo L; Aragão, Karoline S; Magalhães, Carlos Emanuel C; de Carvalho, Cibele B M; Lima, Aldo Ângelo M; Ribeiro, Ronaldo A; Guerrant, Richard L; Moore, Sean R; Oriá, Reinaldo B

    2014-08-05

    WHO guidelines recommend zinc supplementation as a key adjunct therapy for childhood diarrhea in developing countries, however zinc's anti-diarrheal effects remain only partially understood. Recently, it has been recognized that low-grade inflammation may influence stunting. In this study, we examined whether oral zinc supplementation could improve weight, intestinal inflammation, and diarrhea in undernourished weanling rats. Rats were undernourished using a northeastern Brazil regional diet (RBD) for two weeks, followed by oral gavage with a saturated lactose solution (30 g/kg) in the last 7 days to induce osmotic diarrhea. Animals were checked for diarrhea daily after lactose intake. Blood was drawn in order to measure serum zinc levels by atomic absorption spectroscopy. Rats were euthanized to harvest jejunal tissue for histology and cytokine profiles by ELISA. In a subset of animals, spleen samples were harvested under aseptic conditions to quantify bacterial translocation. Oral zinc supplementation increased serum zinc levels following lactose-induced osmotic diarrhea. In undernourished rats, zinc improved weight gain following osmotic diarrhea and significantly reduced diarrheal scores by the third day of lactose intake (p diarrhea and undernutrition and support the use of zinc to prevent the vicious cycle of malnutrition and diarrhea.

  4. Geraniol alleviates LPS-induced acute lung injury in mice via inhibiting inflammation and apoptosis

    Science.gov (United States)

    Jiang, Kangfeng; Zhang, Tao; Yin, Nannan; Ma, Xiaofei; Zhao, Gan; Wu, Haichong; Qiu, Changwei; Deng, Ganzhen

    2017-01-01

    Geraniol (GOH), a special type of acyclic monoterpene alcohol, has been widely used to treat many diseases associated with inflammation and apoptosis. Acute lung injury (ALI) is a common clinical disease in humans characterized by pulmonary inflammation and apoptosis. In the present study, we investigated the protective effects of GOH in a mouse model of ALI induced by the intranasal administration of lipopolysaccharide (LPS) and elucidated the underlying molecular mechanisms in RAW 264.7 cells. In vivo, GOH treatment markedly ameliorated pathological injury and pulmonary cell apoptosis and reduced the wet/dry (W/D) weight ratio of lungs, myeloperoxidase (MPO) activity and the production of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α). In vitro, the levels of pro-inflammatory cytokines, iNOS and COX-2 were significantly increased in LPS-stimulated RAW 264.7 cells, an effect that was decreased by GOH treatment. Moreover, GOH treatment dramatically reduced the expression of Toll-like receptor 4 (TLR4) and then prevented the nuclear factor-κB (NF-κB) activation. GOH treatment also promoted anti-apoptotic Bcl-2 expression and inhibited pro-apoptotic Bax and Caspase-3 expression. Furthermore, knockdown of TLR4 expression exerted a similar effect and inhibited the phosphorylation of p65, as well as the Bax and Caspase-3 expression. Taken together, these results suggest that GOH treatment alleviates LPS-induced ALI via inhibiting pulmonary inflammation and apoptosis, a finding that might be associated with the inhibition of TLR4-mediated NF-κB and Bcl-2/Bax signalling pathways. PMID:29050341

  5. Galantamine alleviates inflammation and insulin resistance in patients with metabolic syndrome in a randomized trial.

    Science.gov (United States)

    Consolim-Colombo, Fernanda M; Sangaleti, Carine T; Costa, Fernando O; Morais, Tercio L; Lopes, Heno F; Motta, Josiane M; Irigoyen, Maria C; Bortoloto, Luiz A; Rochitte, Carlos Eduardo; Harris, Yael Tobi; Satapathy, Sanjaya K; Olofsson, Peder S; Akerman, Meredith; Chavan, Sangeeta S; MacKay, Meggan; Barnaby, Douglas P; Lesser, Martin L; Roth, Jesse; Tracey, Kevin J; Pavlov, Valentin A

    2017-07-20

    Metabolic syndrome (MetS) is an obesity-driven condition of pandemic proportions that increases the risk of type 2 diabetes and cardiovascular disease. Pathophysiological mechanisms are poorly understood, though inflammation has been implicated in MetS pathogenesis. The aim of this study was to assess the effects of galantamine, a centrally acting acetylcholinesterase inhibitor with antiinflammatory properties, on markers of inflammation implicated in insulin resistance and cardiovascular risk, and other metabolic and cardiovascular indices in subjects with MetS. In this randomized, double-blind, placebo-controlled trial, subjects with MetS (30 per group) received oral galantamine 8 mg daily for 4 weeks, followed by 16 mg daily for 8 weeks or placebo. The primary outcome was inflammation assessed through plasma levels of cytokines and adipokines associated with MetS. Secondary endpoints included body weight, fat tissue depots, plasma glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), cholesterol (total, HDL, LDL), triglycerides, BP, heart rate, and heart rate variability (HRV). Galantamine resulted in lower plasma levels of proinflammatory molecules TNF (-2.57 pg/ml [95% CI -4.96 to -0.19]; P = 0.035) and leptin (-12.02 ng/ml [95% CI -17.71 to -6.33]; P < 0.0001), and higher levels of the antiinflammatory molecules adiponectin (2.71 μg/ml [95% CI 1.93 to 3.49]; P < 0.0001) and IL-10 (1.32 pg/ml, [95% CI 0.29 to 2.38]; P = 0.002) as compared with placebo. Galantamine also significantly lowered plasma insulin and HOMA-IR values, and altered HRV. Low-dose galantamine alleviates inflammation and insulin resistance in MetS subjects. These findings support further study of galantamine in MetS therapy. ClinicalTrials.gov, number NCT02283242. Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brazil, and the NIH.

  6. Intestinal Dysbiosis, Barrier Dysfunction, and Bacterial Translocation Account for CKD-Related Systemic Inflammation.

    Science.gov (United States)

    Andersen, Kirstin; Kesper, Marie Sophie; Marschner, Julian A; Konrad, Lukas; Ryu, Mi; Kumar Vr, Santhosh; Kulkarni, Onkar P; Mulay, Shrikant R; Romoli, Simone; Demleitner, Jana; Schiller, Patrick; Dietrich, Alexander; Müller, Susanna; Gross, Oliver; Ruscheweyh, Hans-Joachim; Huson, Daniel H; Stecher, Bärbel; Anders, Hans-Joachim

    2017-01-01

    CKD associates with systemic inflammation, but the underlying cause is unknown. Here, we investigated the involvement of intestinal microbiota. We report that collagen type 4 α3-deficient mice with Alport syndrome-related progressive CKD displayed systemic inflammation, including increased plasma levels of pentraxin-2 and activated antigen-presenting cells, CD4 and CD8 T cells, and Th17- or IFNγ-producing T cells in the spleen as well as regulatory T cell suppression. CKD-related systemic inflammation in these mice associated with intestinal dysbiosis of proteobacterial blooms, translocation of living bacteria across the intestinal barrier into the liver, and increased serum levels of bacterial endotoxin. Uremia did not affect secretory IgA release into the ileum lumen or mucosal leukocyte subsets. To test for causation between dysbiosis and systemic inflammation in CKD, we eradicated facultative anaerobic microbiota with antibiotics. This eradication prevented bacterial translocation, significantly reduced serum endotoxin levels, and fully reversed all markers of systemic inflammation to the level of nonuremic controls. Therefore, we conclude that uremia associates with intestinal dysbiosis, intestinal barrier dysfunction, and bacterial translocation, which trigger the state of persistent systemic inflammation in CKD. Uremic dysbiosis and intestinal barrier dysfunction may be novel therapeutic targets for intervention to suppress CKD-related systemic inflammation and its consequences. Copyright © 2016 by the American Society of Nephrology.

  7. Electroacupuncture Alleviates Pain Responses and Inflammation in a Rat Model of Acute Gout Arthritis

    Directory of Open Access Journals (Sweden)

    Wenxin Chai

    2018-01-01

    Full Text Available Acute gout arthritis is one of the most painful inflammatory conditions. Treatments for gout pain are limited to colchicine, nonsteroidal anti-inflammatory drugs, and corticosteroids, which oftentimes result in severe adverse effects. Electroacupuncture (EA has been proved to be effective in relieving many inflammatory pain conditions with few side effects. Here, we aim to investigate the therapeutic potentials of EA on pain and inflammation of a rat model of acute gout arthritis and underlying mechanisms. We found that 2/100 Hz EA produced the most robust analgesic effect on mechanical hyperalgesia of acute gout arthritis rat model compared with 2 and 100 Hz. EA produced similar analgesic effect compared with indomethacin. 2/100 Hz EA also significantly alleviates the ongoing pain behavior, thermal hyperalgesia, and ankle edema. Locally applied μ and κ-opioid receptor antagonists but not adenosine A1 receptor antagonist significantly abolished the analgesic effect of EA. Locally applied μ and κ-opioid receptor agonists produced significant antiallodynia on acute gout arthritis rats, mimicking EA. Furthermore, 2/100 Hz EA upregulated β-endorphin expression in inflamed ankle skin tissue. Our results demonstrated, for the first time, that EA can be used for relieving acute gout arthritis with effect dependent on peripheral opioid system and comparable with the one obtained with indomethacin.

  8. Absence of intestinal inflammation and postoperative ileus in a mouse model of laparoscopic surgery

    NARCIS (Netherlands)

    Gomez-Pinilla, Pedro J.; Binda, Maria M.; Lissens, Ann; Di Giovangiulio, Martina; van Bree, Sjoerd H.; Nemethova, Andrea; Stakenborg, Nathalie; Farro, Giovanna; Bosmans, Goele; Matteoli, Gianluca; Deprest, Jan; Boeckxstaens, Guy E.

    2014-01-01

    Postoperative ileus (POI) is characterized by impaired gastrointestinal motility resulting from intestinal handling-associated inflammation. The introduction of laparoscopic surgery has dramatically reduced the duration of POI. However, it remains unclear to what extent this results in a reduction

  9. Oral Administration of Escin Inhibits Acute Inflammation and Reduces Intestinal Mucosal Injury in Animal Models

    OpenAIRE

    Li, Minmin; Lu, Chengwen; Zhang, Leiming; Zhang, Jianqiao; Du, Yuan; Duan, Sijin; Wang, Tian; Fu, Fenghua

    2015-01-01

    The present study aimed to investigate the effects of oral administration of escin on acute inflammation and intestinal mucosal injury in animal models. The effects of escin on carrageenan-induced paw edema in a rat model of acute inflammation, cecal ligation and puncture (CLP) induced intestinal mucosal injury in a mouse model, were observed. It was shown that oral administration of escin inhibits carrageenan-induced paw edema and decreases the production of prostaglandin E2 (PGE2) and cyclo...

  10. Study of the effects of dietary polyunsaturated fatty acids: Molecular mechanisms involved intestinal inflammation

    Energy Technology Data Exchange (ETDEWEB)

    Knoch, B.; Barnett, M. P. G.; Roy, N. C.; McNabb, W. C.

    2009-07-01

    The use of omics techniques in combination with model systems and molecular tools allows to understand how foods and food components act on metabolic pathways to regulate transcriptional processes. Polyunsaturated fatty acids have distinctive nutritional and metabolic effects because they give rise to lipid mediated products and affect the expression of various genes involved in intestinal inflammation. The present review focuses on the molecular effects of dietary polyunsaturated fatty acids on intestinal inflammation. (Author) 74 refs.

  11. ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation

    NARCIS (Netherlands)

    Hashimoto, T.; Perlot, T.; Rehman, A.; Trichereau, J.; Ishiguro, H.; Paolino, M.; Sigl, V.; Hanada, T.; Hanada, R.; Lipinski, S.; Wild, B.; Camargo, S.M.; Singer, D.; Richter, A.P.; Kuba, K.; Fukamizu, A.; Schreiber, S.; Clevers, H.; Verrey, F.; Rosenstiel, P.; Penninger, J.M.

    2012-01-01

    Malnutrition affects up to one billion people in the world and is a major cause of mortality. In many cases, malnutrition is associated with diarrhoea and intestinal inflammation, further contributing to morbidity and death. The mechanisms by which unbalanced dietary nutrients affect intestinal

  12. Intestinal handling-induced mast cell activation and inflammation in human postoperative ileus

    NARCIS (Netherlands)

    The, F. O.; Bennink, R. J.; Ankum, W. M.; Buist, M. R.; Busch, O. R. C.; Gouma, D. J.; van der Heide, S.; van den Wijngaard, R. M.; de Jonge, W. J.; Boeckxstaens, G. E.

    2008-01-01

    Background: Murine postoperative ileus results from intestinal inflammation triggered by manipulation-induced mast cell activation. As its extent depends on the degree of handling and subsequent inflammation, it is hypothesised that the faster recovery after minimal invasive surgery results from

  13. Intestinal handling-induced mast cell activation and inflammation in human postoperative ileus

    NARCIS (Netherlands)

    The, F. O.; Bennink, R. J.; Ankum, W. M.; Buist, M. R.; Busch, O. R. C.; Gouma, D. J.; Van der Heide, S.; van den Wijngaard, R. M.; Boeckxstaens, G. E.; de Jonge, Wouter J.

    Background: Murine postoperative ileus results from intestinal inflammation triggered by manipulation-induced mast cell activation. As its extent depends on the degree of handling and subsequent inflammation, it is hypothesised that the faster recovery after minimal invasive surgery results from

  14. Resveratrol alleviate hypoxic pulmonary hypertension via anti-inflammation and anti-oxidant pathways in rats.

    Science.gov (United States)

    Xu, Dunquan; Li, Yan; Zhang, Bo; Wang, Yanxia; Liu, Yi; Luo, Ying; Niu, Wen; Dong, Mingqing; Liu, Manling; Dong, Haiying; Zhao, Pengtao; Li, Zhichao

    2016-01-01

    Resveratrol, a plant-derived polyphenolic compound and a phytoestrogen, was shown to possess multiple protective effects including anti-inflammatory response and anti-oxidative stress. Hypoxic pulmonary hypertension (HPH) is a progressive disease characterized by sustained vascular resistance and marked pulmonary vascular remodeling. The exact mechanisms of HPH are still unclear, but inflammatory response and oxidative stress was demonstrated to participate in the progression of HPH. The present study was designed to investigate the effects of resveratrol on HPH development. Sprague-Dawley rats were challenged by hypoxia exposure for 28 days to mimic hypoxic pulmonary hypertension along with treating resveratrol (40 mg/kg/day). Hemodynamic and pulmonary pathomorphology data were then obtained, and the anti-proliferation effect of resveratrol was determined by in vitro assays. The anti-inflammation and anti-oxidative effects of resveratrol were investigated in vivo and in vitro . The present study showed that resveratrol treatment alleviated right ventricular systolic pressure and pulmonary arterial remodeling induced by hypoxia. In vitro experiments showed that resveratrol notably inhibited proliferation of pulmonary arterial smooth muscle cells in an ER-independent manner. Data showed that resveratrol administration inhibited HIF-1 α expression in vivo and in vitro , suppressed inflammatory cells infiltration around the pulmonary arteries, and decreased ROS production induced by hypoxia in PAMSCs. The inflammatory cytokines' mRNA levels of tumor necrosis factor α, interleukin 6, and interleukin 1β were all suppressed by resveratrol treatment. The in vitro assays showed that resveratrol inhibited the expression of HIF-1 α via suppressing the MAPK/ERK1 and PI3K/AKT pathways. The antioxidant axis of Nuclear factor erythroid-2 related factor 2/ Thioredoxin 1 (Nrf-2/Trx-1) was up-regulated both in lung tissues and in cultured PASMCs. In general, the current study

  15. Aminotriazole alleviates acetaminophen poisoning via downregulating P450 2E1 and suppressing inflammation.

    Directory of Open Access Journals (Sweden)

    Yuping Jing

    Full Text Available Aminotriazole (ATZ is commonly used as a catalase (CAT inhibitor. We previously found ATZ attenuated oxidative liver injury, but the underlying mechanisms remain unknown. Acetaminophen (APAP overdose frequently induces life-threatening oxidative hepatitis. In the present study, the potential hepatoprotective effects of ATZ on oxidative liver injury and the underlying mechanisms were further investigated in a mouse model with APAP poisoning. The experimental data indicated that pretreatment with ATZ dose- and time-dependently suppressed the elevation of plasma aminotransferases in APAP exposed mice, these effects were accompanied with alleviated histological abnormality and improved survival rate of APAP-challenged mice. In mice exposed to APAP, ATZ pretreatment decreased the CAT activities, hydrogen peroxide (H2O2 levels, malondialdehyde (MDA contents, myeloperoxidase (MPO levels in liver and reduced TNF-α levels in plasma. Pretreatment with ATZ also downregulated APAP-induced cytochrome P450 2E1 (CYP2E1 expression and JNK phosphorylation. In addition, posttreatment with ATZ after APAP challenge decreased the levels of plasma aminotransferases and increased the survival rate of experimental animals. Posttreatment with ATZ had no effects on CYP2E1 expression or JNK phosphorylation, but it significantly decreased the levels of plasma TNF-α. Our data indicated that the LD50 of ATZ in mice was 5367.4 mg/kg body weight, which is much higher than the therapeutic dose of ATZ in the present study. These data suggested that ATZ might be effective and safe in protect mice against APAP-induced hepatotoxicity, the beneficial effects might resulted from downregulation of CYP2E1 and inhibiton of inflammation.

  16. Oral Administration of Escin Inhibits Acute Inflammation and Reduces Intestinal Mucosal Injury in Animal Models

    Directory of Open Access Journals (Sweden)

    Minmin Li

    2015-01-01

    Full Text Available The present study aimed to investigate the effects of oral administration of escin on acute inflammation and intestinal mucosal injury in animal models. The effects of escin on carrageenan-induced paw edema in a rat model of acute inflammation, cecal ligation and puncture (CLP induced intestinal mucosal injury in a mouse model, were observed. It was shown that oral administration of escin inhibits carrageenan-induced paw edema and decreases the production of prostaglandin E2 (PGE2 and cyclooxygenase- (COX- 2. In CLP model, low dose of escin ameliorates endotoxin induced liver injury and intestinal mucosal injury and increases the expression of tight junction protein claudin-5 in mice. These findings suggest that escin effectively inhibits acute inflammation and reduces intestinal mucosal injury in animal models.

  17. Oral Administration of Escin Inhibits Acute Inflammation and Reduces Intestinal Mucosal Injury in Animal Models.

    Science.gov (United States)

    Li, Minmin; Lu, Chengwen; Zhang, Leiming; Zhang, Jianqiao; Du, Yuan; Duan, Sijin; Wang, Tian; Fu, Fenghua

    2015-01-01

    The present study aimed to investigate the effects of oral administration of escin on acute inflammation and intestinal mucosal injury in animal models. The effects of escin on carrageenan-induced paw edema in a rat model of acute inflammation, cecal ligation and puncture (CLP) induced intestinal mucosal injury in a mouse model, were observed. It was shown that oral administration of escin inhibits carrageenan-induced paw edema and decreases the production of prostaglandin E2 (PGE2) and cyclooxygenase- (COX-) 2. In CLP model, low dose of escin ameliorates endotoxin induced liver injury and intestinal mucosal injury and increases the expression of tight junction protein claudin-5 in mice. These findings suggest that escin effectively inhibits acute inflammation and reduces intestinal mucosal injury in animal models.

  18. Bacterial antigens alone can influence intestinal barrier integrity, but live bacteria are required for initiation of intestinal inflammation and injury.

    Science.gov (United States)

    Sydora, Beate C; Martin, Sarah M; Lupicki, Maryla; Dieleman, Levinus A; Doyle, Jason; Walker, John W; Fedorak, Richard N

    2006-06-01

    Intestinal flora plays a critical role in the initiation and perpetuation of inflammatory bowel disease. This study examined whether live fecal bacteria were necessary for the initiation of this inflammatory response or whether sterile fecal material would provoke a similar response. Three preparations of fecal material were prepared: (1) a slurry of live fecal bacteria, (2) a sterile lysate of bacterial antigens, and (3) a sterile filtrate of fecal water. Each preparation was introduced via gastric gavage into the intestines of axenic interleukin-10 gene-deficient mice genetically predisposed to develop inflammatory bowel disease. Intestinal barrier integrity and degrees of mucosal and systemic inflammations were determined for each preparation group. Intestinal barrier integrity, as determined by mannitol transmural flux, was altered by both live fecal bacterial and sterile lysates of bacterial antigens, although it was not altered by sterile filtrates of fecal water. However, only live fecal bacteria initiated mucosal inflammation and injury and a systemic immune response. Fecal bacterial antigens in the presence of live bacteria and sterile fecal bacterial antigens have different effects on the initiation and perpetuation of intestinal inflammation.

  19. An innately dangerous balancing act: intestinal homeostasis, inflammation, and colitis-associated cancer

    Science.gov (United States)

    2010-01-01

    Inflammatory bowel disease (IBD) is characterized by dysregulated immune responses to the intestinal microbiota, and by chronic intestinal inflammation. Several recent studies demonstrate the importance of innate microbial recognition by immune and nonimmune cells in the gut. Paradoxically, either diminished or exacerbated innate immune signaling may trigger the breakdown of intestinal homeostasis, leading to IBD and colitis-associated cancer (CAC). This dichotomy may reflect divergent functional roles for immune sensing in intestinal epithelial cells and leukocytes, which may vary with distinct disease mechanisms. PMID:20679404

  20. Oxazolone-Induced Intestinal Inflammation in Adult Zebrafish

    NARCIS (Netherlands)

    Brugman, Sylvia; Nieuwenhuis, EES

    2017-01-01

    Zebrafish are an excellent model for the study of intestinal immunity. The availability of several transgenic reporter fish for different innate and adaptive immune cells and the high homology in terms of gut function and morphology enables in depth analysis of the process of intestinal

  1. Oxazolone-induced intestinal inflammation in adult zebrafish

    NARCIS (Netherlands)

    Brugman, Sylvia; Nieuwenhuis, Edward E.S.

    2017-01-01

    Zebrafish are an excellent model for the study of intestinal immunity. The availability of several transgenic reporter fish for different innate and adaptive immune cells and the high homology in terms of gut function and morphology enables in depth analysis of the process of intestinal

  2. Human intestinal microbiota composition is associated with local and systemic inflammation in obesity.

    Science.gov (United States)

    Verdam, Froukje J; Fuentes, Susana; de Jonge, Charlotte; Zoetendal, Erwin G; Erbil, Runi; Greve, Jan Willem; Buurman, Wim A; de Vos, Willem M; Rensen, Sander S

    2013-12-01

    Intestinal microbiota have been suggested to contribute to the development of obesity, but the mechanism remains elusive. The relationship between microbiota composition, intestinal permeability, and inflammation in nonobese and obese subjects was investigated. Fecal microbiota composition of 28 subjects (BMI 18.6-60.3 kg m(-2) ) was analyzed by a phylogenetic profiling microarray. Fecal calprotectin and plasma C-reactive protein levels were determined to evaluate intestinal and systemic inflammation. Furthermore, HbA1c , and plasma levels of transaminases and lipids were analyzed. Gastroduodenal, small intestinal, and colonic permeability were assessed by a multisaccharide test. Based on microbiota composition, the study population segregated into two clusters with predominantly obese (15/19) or exclusively nonobese (9/9) subjects. Whereas intestinal permeability did not differ between clusters, the obese cluster showed reduced bacterial diversity, a decreased Bacteroidetes/Firmicutes ratio, and an increased abundance of potential proinflammatory Proteobacteria. Interestingly, fecal calprotectin was only detectable in subjects within the obese microbiota cluster (n = 8/19, P = 0.02). Plasma C-reactive protein was also increased in these subjects (P = 0.0005), and correlated with the Bacteroidetes/Firmicutes ratio (rs = -0.41, P = 0.03). Intestinal microbiota alterations in obese subjects are associated with local and systemic inflammation, suggesting that the obesity-related microbiota composition has a proinflammatory effect. Copyright © 2013 The Obesity Society.

  3. Chronic Inflammation in Colorectal Carcinogenesis: Role of Inflammatory Mediators, Intestinal Microbes, and Chemoprevention Potency

    OpenAIRE

    Tedja, Irwin; Abdullah, Murdani

    2013-01-01

    Colorectal carcinogenesis is a multi-factorial process which involves accumulation of genetic defect, protein modification, and cell interaction with matrix in colonic epithelial cells. Chronic inflammation is suspected to play role in carcinogenesis by inhibiting apoptosis, impairing DNA, and chronically stimulating mucosal proliferation. Alteration in intestinal microbes' population, either in one particular species or in overall composition, may also cause chronic inflammation which increa...

  4. Neural reflex pathways in intestinal inflammation: hypotheses to viable therapy

    NARCIS (Netherlands)

    Willemze, Rose A.; Luyer, Misha D.; Buurman, Wim A.; de Jonge, Wouter J.

    2015-01-01

    Studies in neuroscience and immunology have clarified much of the anatomical and cellular basis for bidirectional interactions between the nervous and immune systems. As with other organs, intestinal immune responses and the development of immunity seems to be modulated by neural reflexes.

  5. Myeloid-derived miR-223 regulates intestinal inflammation via repression of the NLRP3 inflammasome

    NARCIS (Netherlands)

    Neudecker, V.; Haneklaus, M.; Jensen, O.; Khailova, L.; Masterson, J.C.; Tye, H.; Biette, K.; Jedlicka, P.; Brodsky, K.S.; Gerich, M.E.; Mack, M.; Robertson, A.A.B.; Cooper, M.A.; Furuta, G.T.; Dinarello, C.A.; O'Neill, L.A.; Eltzschig, H.K.; Masters, S.L.; McNamee, E.N.

    2017-01-01

    MicroRNA (miRNA)-mediated RNA interference regulates many immune processes, but how miRNA circuits orchestrate aberrant intestinal inflammation during inflammatory bowel disease (IBD) is poorly defined. Here, we report that miR-223 limits intestinal inflammation by constraining the nlrp3

  6. Human-derived probiotic Lactobacillus reuteri strains differentially reduce intestinal inflammation.

    Science.gov (United States)

    Liu, Yuying; Fatheree, Nicole Y; Mangalat, Nisha; Rhoads, Jon Marc

    2010-11-01

    Lactobacillus reuteri (L. reuteri) is a probiotic that inhibits the severity of enteric infections and modulates the immune system. Human-derived L. reuteri strains DSM17938, ATCC PTA4659, ATCC PTA 5289, and ATCC PTA 6475 have demonstrated strain-specific immunomodulation in cultured monocytoid cells, but information about how these strains affect inflammation in intestinal epithelium is limited. We determined the effects of the four different L. reuteri strains on lipopolysaccharide (LPS)-induced inflammation in small intestinal epithelial cells and in the ileum of newborn rats. IPEC-J2 cells (derived from the jejunal epithelium of a neonatal piglet) and IEC-6 cells (derived from the rat crypt) were treated with L. reuteri. Newborn rat pups were gavaged cow milk formula supplemented with L. reuteri strains in the presence or absence of LPS. Protein and mRNA levels of cytokines and histological changes were measured. We demonstrate that even though one L. reuteri strain (DSM 17938) did not inhibit LPS-induced IL-8 production in cultured intestinal cells, all strains significantly reduced intestinal mucosal levels of KC/GRO (∼IL-8) and IFN-γ when newborn rat pups were fed formula containing LPS ± L. reuteri. Intestinal histological damage produced by LPS plus cow milk formula was also significantly reduced by all four strains. Cow milk formula feeding (without LPS) produced mild gut inflammation, evidenced by elevated mucosal IFN-γ and IL-13 levels, a process that could be suppressed by strain 17938. Other cytokines and chemokines were variably affected by the different strains, and there was no toxic effect of L. reuteri on intestinal cells or mucosa. In conclusion, L. reuteri strains differentially modulate LPS-induced inflammation. Probiotic interactions with both epithelial and nonepithelial cells in vivo must be instrumental in modulating intrinsic anti-inflammatory effects in the intestine. We suggest that the terms anti- and proinflammatory be used only

  7. Deletion of Foxp3+ regulatory T cells in genetically targeted mice supports development of intestinal inflammation

    Directory of Open Access Journals (Sweden)

    Boehm Franziska

    2012-07-01

    Full Text Available Abstract Background Mice lacking Foxp3+ regulatory T (Treg cells develop severe tissue inflammation in lung, skin, and liver with premature death, whereas the intestine remains uninflamed. This study aims to demonstrate the importance of Foxp3+ Treg for the activation of T cells and the development of intestinal inflammation. Methods Foxp3-GFP-DTR (human diphtheria toxin receptor C57BL/6 mice allow elimination of Foxp3+ Treg by treatment with Dx (diphtheria toxin. The influence of Foxp3+ Treg on intestinal inflammation was tested using the CD4+ T-cell transfer colitis model in Rag−/− C57BL/6 mice and the acute DSS-colitis model. Results Continuous depletion of Foxp3+ Treg in Foxp3-GFP-DTR mice led to dramatic weight loss and death of mice by day 28. After 10 days of depletion of Foxp3+ Treg, isolated CD4+ T-cells were activated and produced extensive amounts of IFN-γ, IL-13, and IL-17A. Transfer of total CD4+ T-cells isolated from Foxp3-GFP-DTR mice did not result in any changes of intestinal homeostasis in Rag−/− C57BL/6 mice. However, administration of DTx between days 14 and 18 after T-cell reconstitution, lead to elimination of Foxp3+ Treg and to immediate weight loss due to intestinal inflammation. This pro-inflammatory effect of Foxp3+ Treg depletion consecutively increased inflammatory cytokine production. Further, the depletion of Foxp3+ Treg from Foxp3-GFP-DTR mice increased the severity of acute dSS-colitis accompanied by 80% lethality of Treg-depleted mice. CD4+ effector T-cells from Foxp3+ Treg-depleted mice produced significantly more pro-inflammatory cytokines. Conclusion Intermittent depletion of Foxp3+ Treg aggravates intestinal inflammatory responses demonstrating the importance of Foxp3+ Treg for the balance at the mucosal surface of the intestine.

  8. Validation study of villous atrophy and small intestinal inflammation in Swedish biopsy registers

    Directory of Open Access Journals (Sweden)

    Montgomery Scott M

    2009-03-01

    Full Text Available Abstract Background Small intestinal biopsy with villous atrophy (VA is the gold standard for the diagnosis of celiac disease (CD. We validated VA (Marsh 3 and small intestinal inflammation without VA (Marsh 1+2 in Swedish regional biopsy registers. Methods All pathology departments in Sweden (n = 28 were searched to identify individuals with VA or duodenal/jejunal inflammation. The validation consisted of blinded examination of biopsy samples, manual review of biopsy reports, web surveys, and patient chart reviews of 121 individuals with VA and 39 with inflammation. Results We identified 29,148 individuals with VA and 13,446 individuals with inflammation. In a blinded examination, Swedish pathologists correctly classified 90% of biopsies with VA. Manual screening of 1,534 biopsy reports (performed by co-author JFL and a research assistant found that comorbidity other than CD was rare. IBD was the most common comorbidity and occurred in 0.3% of biopsies with VA (1.6% in inflammation. Among 114 patients with VA and available data, 108 (95% had a clinical diagnosis of CD. 79% of the validated individuals with VA and 64% of those with inflammation had documented gastrointestinal symptoms prior to biopsy. 88% of the validated individuals with VA had positive CD serology before their first biopsy. 172/180 (96% of Swedish gastroenterologists and 68/68 (100% of pediatricians perform a small intestinal biopsy in at least 9 out of 10 individuals prior to diagnosis of CD. Conclusion Regional biopsy data are feasible to identify individuals with CD and small-intestinal inflammation. The specificity of CD is high in villous atrophy.

  9. Fecal lipocalin 2, a sensitive and broadly dynamic non-invasive biomarker for intestinal inflammation.

    Science.gov (United States)

    Chassaing, Benoit; Srinivasan, Gayathri; Delgado, Maria A; Young, Andrew N; Gewirtz, Andrew T; Vijay-Kumar, Matam

    2012-01-01

    Inflammation has classically been defined histopathologically, especially by the presence of immune cell infiltrates. However, more recent studies suggest a role for "low-grade" inflammation in a variety of disorders ranging from metabolic syndrome to cancer, which is defined by modest elevations in pro-inflammatory gene expression. Consequently, there is a need for cost-effective, non-invasive biomarkers that, ideally, would have the sensitivity to detect low-grade inflammation and have a dynamic range broad enough to reflect classic robust intestinal inflammation. Herein, we report that, for assessment of intestinal inflammation, fecal lipocalin 2 (Lcn-2), measured by ELISA, serves this purpose. Specifically, using a well-characterized mouse model of DSS colitis, we observed that fecal Lcn-2 and intestinal expression of pro-inflammatory cytokines (IL-1β, CXCL1, TNFα) are modestly but significantly induced by very low concentrations of DSS (0.25 and 0.5%), and become markedly elevated at higher concentrations of DSS (1.0 and 4.0%). As expected, careful histopathologic analysis noted only modest immune infiltrates at low DSS concentration and robust colitis at higher DSS concentrations. In accordance, increased levels of the neutrophil product myeloperoxidase (MPO) was only detected in mice given 1.0 and 4.0% DSS. In addition, fecal Lcn-2 marks the severity of spontaneous colitis development in IL-10 deficient mice. Unlike histopathology, MPO, and q-RT-PCR, the assay of fecal Lcn-2 requires only a stool sample, permits measurement over time, and can detect inflammation as early as 1 day following DSS administration. Thus, assay of fecal Lcn-2 by ELISA can function as a non-invasive, sensitive, dynamic, stable and cost-effective means to monitor intestinal inflammation in mice.

  10. Increased Intestinal Inflammation and Digestive Dysfunction in Preterm Pigs with Severe Necrotizing Enterocolitis

    DEFF Research Database (Denmark)

    Støy, Ann Cathrine Findal; Heegaard, Peter M. H.; Skovgaard, Kerstin

    2017-01-01

    The risk factors for necrotizing enterocolitis (NEC) are well known, but the factors involved in the different NEC presentations remain unclear. We hypothesized that digestive dysfunction and intestinal inflammation are mainly affected by severe NEC lesions. In 48 preterm pigs, the association be...

  11. Inhibitors of apoptosis (IAPs) regulate intestinal immunity and inflammatory bowel disease (IBD) inflammation

    DEFF Research Database (Denmark)

    Pedersen, Jannie; LaCasse, Eric C; Seidelin, Jakob B

    2014-01-01

    -linked lymphoproliferative disease type 2 (XLP2), in which 20% of patients develop severe intestinal inflammation. In addition, 4% of males with early-onset IBD also have inactivating mutations in XIAP. Therefore, the IAPs play a greater role in gut homeostasis, immunity and IBD development than previously suspected...

  12. Bovine colostrum improves intestinal function following formula-induced gut inflammation in preterm pigs

    DEFF Research Database (Denmark)

    Støy, Ann Cathrine Findal; Heegaard, Peter M. H.; Thymann, Thomas

    2014-01-01

    , abundance and location of bacteria, and inflammation markers were investigated. Results NEC severity and interleukins (IL)-1β and -8 protein concentrations were lower, while villus height, galactose absorption, and brush-border enzyme activities were increased in the distal small intestine in COLOS...

  13. Fækal calprotectin er en klinisk anvendelig markør for intestinal inflammation

    DEFF Research Database (Denmark)

    Theede, Klaus; Kiszka-Kanowitz, Marianne; Nordgaard-Lassen, Inge

    2014-01-01

    Faecal calprotectin is a biomarker for inflammation in the intestinal mucosa. Faecal calprotectin has the ability to detect inflammatory causes of gastrointestinal symptoms and to distinguish these from irritable bowel syndrome. The test is very sensitive but not specific to any particular...

  14. Irgm1-deficient mice exhibit Paneth cell abnormalities and increased susceptibility to acute intestinal inflammation.

    Science.gov (United States)

    Liu, Bo; Gulati, Ajay S; Cantillana, Viviana; Henry, Stanley C; Schmidt, Elyse A; Daniell, Xiaoju; Grossniklaus, Emily; Schoenborn, Alexi A; Sartor, R Balfour; Taylor, Gregory A

    2013-10-15

    Crohn's disease (CD) is a chronic, immune-mediated, inflammatory disorder of the intestine that has been linked to numerous susceptibility genes, including the immunity-related GTPase (IRG) M (IRGM). IRGs comprise a family of proteins known to confer resistance to intracellular infections through various mechanisms, including regulation of phagosome processing, cell motility, and autophagy. However, despite its association with CD, the role of IRGM and other IRGs in regulating intestinal inflammation is unclear. We investigated the involvement of Irgm1, an ortholog of IRGM, in the genesis of murine intestinal inflammation. After dextran sodium sulfate exposure, Irgm1-deficient [Irgm1 knockout (KO)] mice showed increased acute inflammation in the colon and ileum, with worsened clinical responses. Marked alterations of Paneth cell location and granule morphology were present in Irgm1 KO mice, even without dextran sodium sulfate exposure, and were associated with impaired mitophagy and autophagy in Irgm1 KO intestinal cells (including Paneth cells). This was manifested by frequent tubular and swollen mitochondria and increased LC3-positive autophagic structures. Interestingly, these LC3-positive structures often contained Paneth cell granules. These results suggest that Irgm1 modulates acute inflammatory responses in the mouse intestine, putatively through the regulation of gut autophagic processes, that may be pivotal for proper Paneth cell functioning.

  15. Clinical trial: multispecies probiotic supplementation alleviates the symptoms of IBS and stabilises intestinal microbiota

    NARCIS (Netherlands)

    Kajander, K.; Myllyluoma, E.; Rajlic-Stojanovic, M.; Kyronpalo, S.S.; Rasmussen, M.; Jarvenpaa, S.S.; Zoetendal, E.G.; Vos, de W.M.; Vapaatalo, H.; Korpela, R.

    2008-01-01

    Aim To investigate the effects of multispecies probiotic supplementation (Lactobacillus rhamnosus GG, L. rhamnosus Lc705, Propionibacterium freudenreichii ssp. shermanii JS and Bifidobacterium animalis ssp. lactis Bb12) on abdominal symptoms, quality of life, intestinal microbiota and inflammatory

  16. Crosstalk between Inflammation and ROCK/MLCK Signaling Pathways in Gastrointestinal Disorders with Intestinal Hyperpermeability

    Directory of Open Access Journals (Sweden)

    Lijun Du

    2016-01-01

    Full Text Available The barrier function of the intestine is essential for maintaining the normal homeostasis of the gut and mucosal immune system. Abnormalities in intestinal barrier function expressed by increased intestinal permeability have long been observed in various gastrointestinal disorders such as Crohn’s disease (CD, ulcerative colitis (UC, celiac disease, and irritable bowel syndrome (IBS. Imbalance of metabolizing junction proteins and mucosal inflammation contributes to intestinal hyperpermeability. Emerging studies exploring in vitro and in vivo model system demonstrate that Rho-associated coiled-coil containing protein kinase- (ROCK- and myosin light chain kinase- (MLCK- mediated pathways are involved in the regulation of intestinal permeability. With this perspective, we aim to summarize the current state of knowledge regarding the role of inflammation and ROCK-/MLCK-mediated pathways leading to intestinal hyperpermeability in gastrointestinal disorders. In the near future, it may be possible to specifically target these specific pathways to develop novel therapies for gastrointestinal disorders associated with increased gut permeability.

  17. Naturally occurring glycoalkaloids in potatoes aggravate intestinal inflammation in two mouse models of inflammatory bowel disease.

    Science.gov (United States)

    Iablokov, Vadim; Sydora, Beate C; Foshaug, Rae; Meddings, Jon; Driedger, Darcy; Churchill, Tom; Fedorak, Richard N

    2010-11-01

    Inflammatory bowel disease (IBD) may be initiated following disruption of the intestinal epithelial barrier. This disruption, in turn, permits luminal antigens unfettered access to the mucosal immune system and leads to an uncontrolled inflammatory response. Glycoalkaloids, which are found in potatoes, disrupt cholesterol-containing membranes such as those of the intestinal epithelium. Glycoalkaloid ingestion through potatoes may play a role in the initiation and/or perpetuation of IBD. To determine if commercial and high glycoalkaloids containing fried potato skins aggravate intestinal inflammation using two different animal models of IBD. Fried potato skins from commercial potatoes containing low/medium glycoalkaloid levels and high glycoalkaloids potatoes were fed for 20 days to interleukin 10 gene-deficient mice and dextran sodium sulfate-induced colitic mice. Intestinal permeability, mucosal cytokine and myeloperoxidase levels and body weight were determined to assess intestinal injury. Deep frying potato skins markedly increased glycoalkaloid content. Interleukin 10 gene-deficient mice fed fried commercial potato skins with medium glycoalkaloid content exhibited significantly elevated levels of ileal IFN-γ relative to controls. Mice in the dextran sodium sulfate colitis model that were fed the same strain of potatoes demonstrated significantly elevated levels of pro-inflammatory cytokines IFN-γ, TNF-α, and IL-17 in the colon in addition to an enhanced colonic permeability. Inflammatory response was intensified when the mice were fed potatoes with higher glycoalkaloid contents. Our results demonstrate that consumption of potato skins containing glycoalkaloids can significantly aggravate intestinal inflammation in predisposed individuals.

  18. Intestinal exposure to PCB 153 induces inflammation via the ATM/NEMO pathway.

    Science.gov (United States)

    Phillips, Matthew C; Dheer, Rishu; Santaolalla, Rebeca; Davies, Julie M; Burgueño, Juan; Lang, Jessica K; Toborek, Michal; Abreu, Maria T

    2018-01-15

    Polychlorinated biphenyls (PCBs) are persistent organic pollutants that adversely affect human health. PCBs bio-accumulate in organisms important for human consumption. PCBs accumulation in the body leads to activation of the transcription factor NF-κB, a major driver of inflammation. Despite dietary exposure being one of the main routes of exposure to PCBs, the gut has been widely ignored when studying the effects of PCBs. We investigated the effects of PCB 153 on the intestine and addressed whether PCB 153 affected intestinal permeability or inflammation and the mechanism by which this occurred. Mice were orally exposed to PCB 153 and gut permeability was assessed. Intestinal epithelial cells (IECs) were collected and evaluated for evidence of genotoxicity and inflammation. A human IEC line (SW480) was used to examine the direct effects of PCB 153 on epithelial function. NF-кB activation was measured using a reporter assay, DNA damage was assessed, and cytokine expression was ascertained with real-time PCR. Mice orally exposed to PCB 153 had an increase in intestinal permeability and inflammatory cytokine expression in their IECs; inhibition of NF-кB ameliorated both these effects. This inflammation was associated with genotoxic damage and NF-кB activation. Exposure of SW480 cells to PCB 153 led to similar effects as seen in vivo. We found that activation of the ATM/NEMO pathway by genotoxic stress was upstream of NF-kB activation. These results demonstrate that oral exposure to PCB 153 is genotoxic to IECs and induces downstream inflammation and barrier dysfunction in the intestinal epithelium. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Disrupted intestinal microbiota and intestinal inflammation in children with cystic fibrosis and its restoration with Lactobacillus GG: a randomised clinical trial.

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    Eugenia Bruzzese

    Full Text Available Intestinal inflammation is a hallmark of cystic fibrosis (CF. Administration of probiotics can reduce intestinal inflammation and the incidence of pulmonary exacerbations. We investigated the composition of intestinal microbiota in children with CF and analyzed its relationship with intestinal inflammation. We also investigated the microflora structure before and after Lactobacillus GG (LGG administration in children with CF with and without antibiotic treatment.The intestinal microbiota were analyzed by denaturing gradient gel electrophoresis (DGGE, real-time polymerase chain reaction (RT-PCR, and fluorescence in situ hybridization (FISH. Intestinal inflammation was assessed by measuring fecal calprotectin (CLP and rectal nitric oxide (rNO production in children with CF as compared with healthy controls. We then carried out a small double-blind randomized clinical trial with LGG.Twenty-two children with CF children were enrolled in the study (median age, 7 years; range, 2-9 years. Fecal CLP and rNO levels were higher in children with CF than in healthy controls (184±146 µg/g vs. 52±46 µg/g; 18±15 vs. 2.6±1.2 µmol/L NO2 (-, respectively; P<0.01. Compared with healthy controls, children with CF had significantly different intestinal microbial core structures. The levels of Eubacterium rectale, Bacteroides uniformis, Bacteroides vulgatus, Bifidobacterium adolescentis, Bifidobacterium catenulatum, and Faecalibacterium prausnitzii were reduced in children with CF. A similar but more extreme pattern was observed in children with CF who were taking antibiotics. LGG administration reduced fecal CLP and partially restored intestinal microbiota. There was a significant correlation between reduced microbial richness and intestinal inflammation.CF causes qualitative and quantitative changes in intestinal microbiota, which may represent a novel therapeutic target in the treatment of CF. Administration of probiotics restored gut microbiota, supporting

  20. Disrupted intestinal microbiota and intestinal inflammation in children with cystic fibrosis and its restoration with Lactobacillus GG: a randomised clinical trial.

    Science.gov (United States)

    Bruzzese, Eugenia; Callegari, Maria Luisa; Raia, Valeria; Viscovo, Sara; Scotto, Riccardo; Ferrari, Susanna; Morelli, Lorenzo; Buccigrossi, Vittoria; Lo Vecchio, Andrea; Ruberto, Eliana; Guarino, Alfredo

    2014-01-01

    Intestinal inflammation is a hallmark of cystic fibrosis (CF). Administration of probiotics can reduce intestinal inflammation and the incidence of pulmonary exacerbations. We investigated the composition of intestinal microbiota in children with CF and analyzed its relationship with intestinal inflammation. We also investigated the microflora structure before and after Lactobacillus GG (LGG) administration in children with CF with and without antibiotic treatment. The intestinal microbiota were analyzed by denaturing gradient gel electrophoresis (DGGE), real-time polymerase chain reaction (RT-PCR), and fluorescence in situ hybridization (FISH). Intestinal inflammation was assessed by measuring fecal calprotectin (CLP) and rectal nitric oxide (rNO) production in children with CF as compared with healthy controls. We then carried out a small double-blind randomized clinical trial with LGG. Twenty-two children with CF children were enrolled in the study (median age, 7 years; range, 2-9 years). Fecal CLP and rNO levels were higher in children with CF than in healthy controls (184±146 µg/g vs. 52±46 µg/g; 18±15 vs. 2.6±1.2 µmol/L NO2 (-), respectively; P<0.01). Compared with healthy controls, children with CF had significantly different intestinal microbial core structures. The levels of Eubacterium rectale, Bacteroides uniformis, Bacteroides vulgatus, Bifidobacterium adolescentis, Bifidobacterium catenulatum, and Faecalibacterium prausnitzii were reduced in children with CF. A similar but more extreme pattern was observed in children with CF who were taking antibiotics. LGG administration reduced fecal CLP and partially restored intestinal microbiota. There was a significant correlation between reduced microbial richness and intestinal inflammation. CF causes qualitative and quantitative changes in intestinal microbiota, which may represent a novel therapeutic target in the treatment of CF. Administration of probiotics restored gut microbiota, supporting the

  1. Lactobacillus rhamnosus GG Intake Modifies Preschool Children's Intestinal Microbiota, Alleviates Penicillin-Associated Changes, and Reduces Antibiotic Use.

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    Katri Korpela

    Full Text Available Antibiotic use is considered among the most severe causes of disturbance to children's developing intestinal microbiota, and frequently causes adverse gastrointestinal effects ranging from mild and transient diarrhoea to life-threatening infections. Probiotics are commonly advocated to help in preventing antibiotic-associated gastrointestinal symptoms. However, it is currently unknown whether probiotics alleviate the antibiotic-associated changes in children's microbiota. Furthermore, it is not known how long-term probiotic consumption influences the developing microbiota of children. We analysed the influence of long-term Lactobacillus rhamnosus GG intake on preschool children's antibiotic use, and antibiotic-associated gastrointestinal complaints in a double blind, randomized placebo-controlled trial with 231 children aged 2-7. In addition, we analysed the effect of L. rhanmosus GG on the intestinal microbiota in a subset of 88 children. The results show that long-term L. rhamnosus GG supplementation has an influence on the composition of the intestinal microbiota in children, causing an increase in the abundance of Prevotella, Lactococcus, and Ruminococcus, and a decrease in Escherichia. The treatment appeared to prevent some of the changes in the microbiota associated with penicillin use, but not those associated with macrolide use. The treatment, however, did reduce the frequency of gastrointestinal complaints after a macrolide course. Finally, the treatment appeared to prevent certain bacterial infections for up to 3 years after the trial, as indicated by reduced antibiotic use.ClinicalTrials.gov NCT01014676.

  2. Lactobacillus rhamnosus GG Intake Modifies Preschool Children’s Intestinal Microbiota, Alleviates Penicillin-Associated Changes, and Reduces Antibiotic Use

    Science.gov (United States)

    Korpela, Katri; Salonen, Anne; Virta, Lauri J.; Kumpu, Minna; Kekkonen, Riina A.; de Vos, Willem M.

    2016-01-01

    Antibiotic use is considered among the most severe causes of disturbance to children’s developing intestinal microbiota, and frequently causes adverse gastrointestinal effects ranging from mild and transient diarrhoea to life-threatening infections. Probiotics are commonly advocated to help in preventing antibiotic-associated gastrointestinal symptoms. However, it is currently unknown whether probiotics alleviate the antibiotic-associated changes in children’s microbiota. Furthermore, it is not known how long-term probiotic consumption influences the developing microbiota of children. We analysed the influence of long-term Lactobacillus rhamnosus GG intake on preschool children’s antibiotic use, and antibiotic-associated gastrointestinal complaints in a double blind, randomized placebo-controlled trial with 231 children aged 2–7. In addition, we analysed the effect of L. rhanmosus GG on the intestinal microbiota in a subset of 88 children. The results show that long-term L. rhamnosus GG supplementation has an influence on the composition of the intestinal microbiota in children, causing an increase in the abundance of Prevotella, Lactococcus, and Ruminococcus, and a decrease in Escherichia. The treatment appeared to prevent some of the changes in the microbiota associated with penicillin use, but not those associated with macrolide use. The treatment, however, did reduce the frequency of gastrointestinal complaints after a macrolide course. Finally, the treatment appeared to prevent certain bacterial infections for up to 3 years after the trial, as indicated by reduced antibiotic use. Trial Registration: ClinicalTrials.gov NCT01014676 PMID:27111772

  3. Lactobacillus rhamnosus GG Intake Modifies Preschool Children's Intestinal Microbiota, Alleviates Penicillin-Associated Changes, and Reduces Antibiotic Use.

    Science.gov (United States)

    Korpela, Katri; Salonen, Anne; Virta, Lauri J; Kumpu, Minna; Kekkonen, Riina A; de Vos, Willem M

    2016-01-01

    Antibiotic use is considered among the most severe causes of disturbance to children's developing intestinal microbiota, and frequently causes adverse gastrointestinal effects ranging from mild and transient diarrhoea to life-threatening infections. Probiotics are commonly advocated to help in preventing antibiotic-associated gastrointestinal symptoms. However, it is currently unknown whether probiotics alleviate the antibiotic-associated changes in children's microbiota. Furthermore, it is not known how long-term probiotic consumption influences the developing microbiota of children. We analysed the influence of long-term Lactobacillus rhamnosus GG intake on preschool children's antibiotic use, and antibiotic-associated gastrointestinal complaints in a double blind, randomized placebo-controlled trial with 231 children aged 2-7. In addition, we analysed the effect of L. rhanmosus GG on the intestinal microbiota in a subset of 88 children. The results show that long-term L. rhamnosus GG supplementation has an influence on the composition of the intestinal microbiota in children, causing an increase in the abundance of Prevotella, Lactococcus, and Ruminococcus, and a decrease in Escherichia. The treatment appeared to prevent some of the changes in the microbiota associated with penicillin use, but not those associated with macrolide use. The treatment, however, did reduce the frequency of gastrointestinal complaints after a macrolide course. Finally, the treatment appeared to prevent certain bacterial infections for up to 3 years after the trial, as indicated by reduced antibiotic use. ClinicalTrials.gov NCT01014676.

  4. Lipides et inflammation postprandiale : impact du microbiote intestinal

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    Cani Patrice D.

    2011-01-01

    Full Text Available Obesity and type 2 diabetes are associated with low grade inflammatory tone. Evidence suggest that the gut microbiota could be involved not only in the host metabolism but also in the pathogenesis of the low grade inflammation associated with obesity and type 2 diabetes. Among the mechanisms, dietary habits and more specifically the nutritional composition of the diet (lipids, non digestibles carbohydrates have been shown to participate to the modulation of the composition and/or the activity of the gut microbiota. These questions and mechanisms will be discussed following experimental data.

  5. Control of Paneth Cell Fate, Intestinal Inflammation, and Tumorigenesis by PKCλ/ι

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    Yuki Nakanishi

    2016-09-01

    Full Text Available Paneth cells are a highly specialized population of intestinal epithelial cells located in the crypt adjacent to Lgr5+ stem cells, from which they differentiate through a process that requires downregulation of the Notch pathway. Their ability to store and release antimicrobial peptides protects the host from intestinal pathogens and controls intestinal inflammation. Here, we show that PKCλ/ι is required for Paneth cell differentiation at the level of Atoh1 and Gfi1, through the control of EZH2 stability by direct phosphorylation. The selective inactivation of PKCλ/ι in epithelial cells results in the loss of mature Paneth cells, increased apoptosis and inflammation, and enhanced tumorigenesis. Importantly, PKCλ/ι expression in human Paneth cells decreases with progression of Crohn’s disease. Kaplan-Meier survival analysis of colorectal cancer (CRC patients revealed that low PRKCI levels correlated with significantly worse patient survival rates. Therefore, PKCλ/ι is a negative regulator of intestinal inflammation and cancer through its role in Paneth cell homeostasis.

  6. VESGEN Mapping of Bioactive Protection against Intestinal Inflammation: Application to Human Spaceflight and ISS Experiments

    Science.gov (United States)

    Parsons-Wingerter, P. A.; Chen, X.; Kelly, C. P.; Reinecker, H. C.

    2011-01-01

    Challenges to successful space exploration and colonization include adverse physiological reactions to micro gravity and space radiation factors. Constant remodeling of the microvasculature is critical for tissue preservation, wound healing, and recovery after ischemia. Regulation of the vascular system in the intestine is particularly important to enable nutrient absorption while maintaining barrier function and mucosal defense against micro biota. Although tremendous progress has been made in understanding the molecular circuits regulating neovascularization, our knowledge of the adaptations of the vascular system to environmental challenges in the intestine remains incomplete. This is in part because of the lack of methods to observe and quantify the complex processes associated with vascular responses in vivo. Developed by GRC as a mature beta version, pre-release research software, VESsel GENeration Analysis (VESGEN) maps and quantifies the fractal-based complexity of vascular branching for novel insights into the cytokine, transgenic and therapeutic regulation of angiogenesis, lymphangiogenesis and microvascular remodeling. Here we demonstrate that VESGEN can be used to characterize the dynamic vascular responses to acute intestinal inflammation and mucosal recovery from in vivo confocal microscopic 3D image series. We induced transient intestinal inflammation in mice by DSS treatment and investigated whether the ability of the pro biotic yeast Saccharomyces boulardii (Sb) to protect against intestinal inflammation was due to regulation of vascular remodeling. A primary characteristic of inflammation is excessive neovascularization (angiogenesis) resulting in fragile vessels prone to bleeding. Morphological parameters for triplicate specimens revealed that Sb treatment greatly reduced the inflammatory response of vascular networks by an average of 78%. This resulted from Sb inhibition of vascular endothelial growth factor receptor signaling, a major

  7. Bacterial overgrowth and inflammation of small intestine after carboxymethylcellulose ingestion in genetically susceptible mice.

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    Swidsinski, Alexander; Ung, Victoria; Sydora, Beate C; Loening-Baucke, Vera; Doerffel, Yvonne; Verstraelen, Hans; Fedorak, Richard N

    2009-03-01

    Detergents and emulsifiers added to food may destroy the mucus barrier, which normally isolates bacteria from the intestinal wall, and lead to chronic bowel inflammation in susceptible persons. We investigated the influence of 2% carboxymethylcellulose (CMC) on the biostructure of the intestinal microbiota in IL-10 gene-deficient mice. Twenty to 27-week-old IL-10 gene-deficient mice received either 2% CMC solution (n = 7) or water (n = 6) orally for 3 weeks. Intestinal bacteria were investigated using fluorescence in situ hybridization in paraffin-fixed sections of the intestine. CMC-treated IL-10 gene-deficient mice demonstrated a massive bacterial overgrowth, distention of spaces between villi, with bacteria filling these spaces, adherence of bacteria to the mucosa, and migration of bacteria to the bottom of the crypts of Lieberkuehn. Leukocytes migrated into the intestinal lumen in 4 of the 7 CMC mice. The changes were similar to those observed in Crohn's disease in humans and were absent in control animals. CMC induces bacterial overgrowth and small bowel inflammation in susceptible animals. Because of its ubiquity in products and its unrestricted use in food of the industrial world, CMC is an ideal suspect to account for the rise of IBD in the 20th century.

  8. Autophagy protects intestinal epithelial cells against deoxynivalenol toxicity by alleviating oxidative stress via IKK signaling pathway.

    Science.gov (United States)

    Tang, Yulong; Li, Jianjun; Li, Fengna; Hu, Chien-An A; Liao, Peng; Tan, Kunrong; Tan, Bie; Xiong, Xia; Liu, Gang; Li, Tiejun; Yin, Yulong

    2015-12-01

    Autophagy is an intracellular process of homeostatic degradation that promotes cell survival under various stressors. Deoxynivalenol (DON), a fungal toxin, often causes diarrhea and disturbs the homeostasis of the intestinal system. To investigate the function of intestinal autophagy in response to DON and associated mechanisms, we firstly knocked out ATG5 (autophagy-related gene 5) in porcine intestinal epithelial cells (IPEC-J2) using CRISPR-Cas9 technology. When treated with DON, autophagy was induced in IPEC-J2 cells but not in IPEC-J2.Atg5ko cells. The deficiency in autophagy increased DON-induced apoptosis in IPEC-J2.atg5ko cells, in part, through the generation of reactive oxygen species (ROS). The cellular stress response can be restored in IPEC-J2.atg5ko cells by overexpressing proteins involved in protein folding. Interestingly, we found that autophagy deficiency downregulated the expression of endoplasmic reticulum folding proteins BiP and PDI when IPEC-J2.atg5ko cells were treated with DON. In addition, we investigated the molecular mechanism of autophagy involved in the IKK, AMPK, and mTOR signaling pathway and found that Bay-117082 and Compound C, specific inhibitors for IKK and AMPK, respectively, inhibited the induction of autophagy. Taken together, our results suggest that autophagy is pivotal for protection against DON in pig intestinal cells. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Chrysin alleviates testicular dysfunction in adjuvant arthritic rats via suppression of inflammation and apoptosis: Comparison with celecoxib

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    Darwish, Hebatallah A. [Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo 11562 (Egypt); Arab, Hany H., E-mail: hany.arab@pharma.cu.edu.eg [Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo 11562 (Egypt); Abdelsalam, Rania M. [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo 11562 (Egypt)

    2014-09-01

    Long standing rheumatoid arthritis (RA) is associated with testicular dysfunction and subfertility. Few studies have addressed the pathogenesis of testicular injury in RA and its modulation by effective agents. Thus, the current study aimed at evaluating the effects of two testosterone boosting agents; chrysin, a natural flavone and celecoxib, a selective COX-2 inhibitor, in testicular impairment in rats with adjuvant arthritis, an experimental model of RA. Chrysin (25 and 50 mg/kg) and celecoxib (5 mg/kg) were orally administered to Wistar rats once daily for 21 days starting 1 h before arthritis induction. Chrysin suppressed paw edema with comparable efficacy to celecoxib. More important, chrysin, dose-dependently and celecoxib attenuated the testicular injury via reversing lowered gonadosomatic index and histopathologic alterations with preservation of spermatogenesis. Both agents upregulated steroidogenic acute regulatory (StAR) mRNA expression and serum testosterone with concomitant restoration of LH and FSH. Furthermore, they suppressed inflammation via abrogation of myeloperoxidase, TNF-α and protein expression of COX-2 and iNOS besides elevation of IL-10. Alleviation of the testicular impairment was accompanied with suppression of oxidative stress via lowering testicular lipid peroxides and nitric oxide. With respect to apoptosis, both agents downregulated FasL mRNA expression and caspase-3 activity in favor of cell survival. For the first time, these findings highlight the protective effects of chrysin and celecoxib against testicular dysfunction in experimental RA which were mediated via boosting testosterone in addition to attenuation of testicular inflammation, oxidative stress and apoptosis. Generally, the 50 mg/kg dose of chrysin exerted comparable protective actions to celecoxib. - Highlights: • Chrysin and celecoxib alleviated testicular suppression in adjuvant arthritis. • They attenuated histopathological damage and preserved spermatogenesis

  10. Dried Human Amniotic Membrane Does Not Alleviate Inflammation and Fibrosis in Experimental Strabismus Surgery

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    Bo Young Chun

    2013-01-01

    Full Text Available Purpose. The purpose of this study was to evaluate the efficacy of dried human amniotic membrane (AM in reducing the postoperative inflammatory response and scarring after strabismus surgery. Methods. The inflammatory response at the extraocular muscle reattachment site was analyzed after superior rectus (SR resection in 12 rabbits. Dried human AM (Ambiodry2 was applied between the resected SR muscle plane and Tenon’s capsule of the left eyes of rabbits. As a control, the right eyes of rabbits underwent SR resection only. The surgeon randomly ordered which eye gets operated first during the experiment. Two weeks later, enucleation was performed. Six sagittal sections were made for each eye at the insertion of the SR muscle. The grade of postoperative inflammation and the presence of fibrosis were evaluated in histological examinations. Results. There was no statistically significant difference in the intensity of inflammation and fibrous proliferation between the eyes treated with dried human AM after SR resection and those treated with SR resection only. Conclusions. The use of dried human AM was not effective in controlling the postoperative inflammation and scarring in rabbit eyes after extraocular muscle surgery. However, this may be due to the devitalized dry preparation of human AM (Ambiodry2, which may have lost the expected anti-inflammatory and anti-scarring properties, and further studies on humans may be necessary.

  11. MMP-3 Deficiency Alleviates Endotoxin-Induced Acute Inflammation in the Posterior Eye Segment

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    Inge Van Hove

    2016-11-01

    Full Text Available Matrix metalloproteinase-3 (MMP-3 is known to mediate neuroinflammatory processes by activating microglia, disrupting blood–central nervous system barriers and supporting neutrophil influx into the brain. In addition, the posterior part of the eye, more specifically the retina, the retinal pigment epithelium (RPE and the blood–retinal barrier, is affected upon neuroinflammation, but a role for MMP-3 during ocular inflammation remains elusive. We investigated whether MMP-3 contributes to acute inflammation in the eye using the endotoxin-induced uveitis (EIU model. Systemic administration of lipopolysaccharide induced an increase in MMP-3 mRNA and protein expression level in the posterior part of the eye. MMP-3 deficiency or knockdown suppressed retinal leukocyte adhesion and leukocyte infiltration into the vitreous cavity in mice subjected to EIU. Moreover, retinal and RPE mRNA levels of intercellular adhesion molecule 1 (Icam1, interleukin 6 (Il6, cytokine-inducible nitrogen oxide synthase (Nos2 and tumor necrosis factor α (Tnfα, which are key molecules involved in EIU, were clearly reduced in MMP-3 deficient mice. In addition, loss of MMP-3 repressed the upregulation of the chemokines monocyte chemoattractant protein (MCP-1 and (C-X-C motif ligand 1 (CXCL1. These findings suggest a contribution of MMP-3 during EIU, and its potential use as a therapeutic drug target in reducing ocular inflammation.

  12. Essential oil from waste leaves of Curcuma longa L. alleviates skin inflammation.

    Science.gov (United States)

    Kumar, Anant; Agarwal, Karishma; Singh, Monika; Saxena, Archana; Yadav, Pankaj; Maurya, Anil Kumar; Yadav, Anju; Tandon, Sudeep; Chanda, Debabrata; Bawankule, Dnyaneshwar U

    2018-02-10

    Curcuma longa L. is an important industrial crop used by medicinal and cosmetic industries in the world. Its leaves are a waste material after harvesting rhizomes. The aim of the study was to evaluate the chemical and pharmacological profile of essential oil from waste leaves of Curcuma longa (EOCl) against skin inflammation. EOCl was subjected to gas chromatography (GC) analysis for identification of essential oil constituents and its anti-inflammatory evaluation through in vitro and in vivo models. Chemical fingerprinting using GC and GC-MS analysis of EOCl revealed the presence of 11 compounds, representing 90.29% of the oil, in which terpinolene (52.88%) and α-phellandrene (21.13%) are the major components. In the in vitro testing EOCl inhibited the production of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) in lipopolysaccharide (LPS) and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation in the human keratinocyte cell line (HaCaT). Topical application of EOCl produced anti-inflammatory effects by reducing ear thickness, ear weight and ameliorating the level of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) at protein and mRNA levels as well as regulating the overproduction of oxidative markers and restoring the histopathological damage in a TPA-induced mouse model of inflammation. These findings of topical anti-inflammatory properties of EOCl provide a scientific basis for medicinal use of this plant material against inflammatory disorders.

  13. Faecal calprotectin: a marker of inflammation throughout the intestinal tract.

    Science.gov (United States)

    Summerton, Christopher B; Longlands, Michael G; Wiener, Keith; Shreeve, David R

    2002-08-01

    To assess the potential of measuring the calcium-binding protein calprotectin in faeces as a method of screening for alimentary inflammation and neoplasia. Hospital day services unit for endoscopy and faecal analysis in the clinical biochemistry department. Consented patients attending for routine endoscopy were requested to provide faeces. Seventeen of the initial 30 patients provided faeces before and 1 week after endoscopy. After this, 116 patients for planned endoscopy provided faeces before endoscopy. The group comprised 43 patients with upper-gastrointestinal lesions, seven patients with inflammatory bowel disease, seven patients with irritable bowel syndrome, 31 patients with colonic disorders, and 28 normal people. A final 18 patients with known inflammatory bowel disease (seven patients), gastric carcinoma (one patient), colorectal cancer (eight patients) and colorectal adenoma (two patients) had faeces analysed. Faeces were analysed by the Nycotest PhiCal enzyme-linked immunosorbent assay (ELISA) (Nycomed, Oslo, Norway), and the final 18 patients were analysed by the newer version marketed as Calprest. No definite differences between pre- and post-endoscopy calprotectin were found, but it was considered preferable in the subsequent patients to analyse pre-endoscopy faeces. Upper-gastrointestinal disorders showed little difference in calprotectin levels, Barrett's oesophagus (median 6.8 mg/l), gastric ulcer (median 6.5 mg/l) or gastritis/duodenitis (median 5.2 mg/l), but these levels were all higher than the median calprotectin level of normal subjects (4.5 mg/l). The oesophageal and gastric carcinoma median was elevated significantly at 30 mg/l. Inflammatory bowel disease was also associated with marked elevation (Crohn's disease, 31.2 mg/l; ulcerative colitis, 116.2 mg/l). Colorectal polyps (median 3.7 mg/l) and adenoma (median 3.8 mg/l) showed no elevated levels in contrast to colorectal carcinoma (median 53.4 mg/l). The elevated calprotectin in

  14. Intestinal Disaccharidase Activity in Patients with Autism: Effect of Age, Gender, and Intestinal Inflammation

    Science.gov (United States)

    Kushak, Rafail I.; Lauwers, Gregory Y.; Winter, Harland S.; Buie, Timothy M.

    2011-01-01

    Intestinal disaccharidase activities were measured in 199 individuals with autism to determine the frequency of enzyme deficiency. All patients had duodenal biopsies that were evaluated morphologically and assayed for lactase, sucrase, and maltase activity. Frequency of lactase deficiency was 58% in autistic children less than or equal to 5 years…

  15. Gut-associated lymphoid tissue, T cell trafficking, and chronic intestinal inflammation.

    Science.gov (United States)

    Koboziev, Iurii; Karlsson, Fridrik; Grisham, Matthew B

    2010-10-01

    The etiologies of the inflammatory bowel diseases (IBD; Crohn's disease, ulcerative colitis) have not been fully elucidated. However, there is very good evidence implicating T cell and T cell trafficking to the gut and its associated lymphoid tissue as important components in disease pathogenesis. The objective of this review is to provide an overview of the mechanisms involved in naive and effector T cell trafficking to the gut-associated lymphoid tissue (GALT; Peyer's patches, isolated lymphoid follicles), mesenteric lymph nodes and intestine in response to commensal enteric antigens under physiological conditions as well as during the induction of chronic gut inflammation. In addition, recent data suggests that the GALT may not be required for enteric antigen-driven intestinal inflammation in certain mouse models of IBD. These new data suggest a possible paradigm shift in our understanding of how and where naive T cells become activated to yield disease-producing effector cells. © 2010 New York Academy of Sciences.

  16. Mast cell stabilization alleviates acute lung injury after orthotopic autologous liver transplantation in rats by downregulating inflammation.

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    Ailan Zhang

    Full Text Available BACKGROUND: Acute lung injury (ALI is one of the most severe complications after orthotopic liver transplantation. Amplified inflammatory response after transplantation contributes to the process of ALI, but the mechanism underlying inflammation activation is not completely understood. We have demonstrated that mast cell stabilization attenuated inflammation and ALI in a rodent intestine ischemia/reperfusion model. We hypothesized that upregulation of inflammation triggered by mast cell activation may be involve in ALI after liver transplantation. METHODS: Adult male Sprague-Dawley rats received orthotopic autologous liver transplantation (OALT and were executed 4, 8, 16, and 24 h after OALT. The rats were pretreated with the mast cell stabilizers cromolyn sodium or ketotifen 15 min before OALT and executed 8 h after OALT. Lung tissues and arterial blood were collected to evaluate lung injury. β-hexosaminidase and mast cell tryptase levels were assessed to determine the activation of mast cells. Tumor necrosis factor α (TNF-α, interleukin (IL-1β and IL-6 in serum and lung tissue were analyzed by enzyme-linked immunosorbent assay. Nuclear factor-kappa B (NF-κB p65 translocation was assessed by Western blot. RESULTS: The rats that underwent OALT exhibited severe pulmonary damage with a high wet-to-dry ratio, low partial pressure of oxygen, and low precursor surfactant protein C levels, which corresponded to the significant elevation of pro-inflammatory cytokines, β-hexosaminidase, and tryptase levels in serum and lung tissues. The severity of ALI progressed and maximized 8 h after OALT. Mast cell stabilization significantly inhibited the activation of mast cells, downregulated pro-inflammatory cytokine levels and translocation of NF-κB, and attenuated OALT-induced ALI. CONCLUSIONS: Mast cell activation amplified inflammation and played an important role in the process of post-OALT related ALI.

  17. Histamine H2 Receptor-Mediated Suppression of Intestinal Inflammation by Probiotic Lactobacillus reuteri.

    Science.gov (United States)

    Gao, Chunxu; Major, Angela; Rendon, David; Lugo, Monica; Jackson, Vanessa; Shi, Zhongcheng; Mori-Akiyama, Yuko; Versalovic, James

    2015-12-15

    Probiotics and commensal intestinal microbes suppress mammalian cytokine production and intestinal inflammation in various experimental model systems. Limited information exists regarding potential mechanisms of probiotic-mediated immunomodulation in vivo. In this report, we demonstrate that specific probiotic strains of Lactobacillus reuteri suppress intestinal inflammation in a trinitrobenzene sulfonic acid (TNBS)-induced mouse colitis model. Only strains that possess the hdc gene cluster, including the histidine decarboxylase and histidine-histamine antiporter genes, can suppress colitis and mucosal cytokine (interleukin-6 [IL-6] and IL-1β in the colon) gene expression. Suppression of acute colitis in mice was documented by diminished weight loss, colonic injury, serum amyloid A (SAA) protein concentrations, and reduced uptake of [(18)F]fluorodeoxyglucose ([(18)F]FDG) in the colon by positron emission tomography (PET). The ability of probiotic L. reuteri to suppress colitis depends on the presence of a bacterial histidine decarboxylase gene(s) in the intestinal microbiome, consumption of a histidine-containing diet, and signaling via the histamine H2 receptor (H2R). Collectively, luminal conversion of l-histidine to histamine by hdc(+) L. reuteri activates H2R, and H2R signaling results in suppression of acute inflammation within the mouse colon. Probiotics are microorganisms that when administered in adequate amounts confer beneficial effects on the host. Supplementation with probiotic strains was shown to suppress intestinal inflammation in patients with inflammatory bowel disease and in rodent colitis models. However, the mechanisms of probiosis are not clear. Our current studies suggest that supplementation with hdc(+) L. reuteri, which can convert l-histidine to histamine in the gut, resulted in suppression of colonic inflammation. These findings link luminal conversion of dietary components (amino acid metabolism) by gut microbes and probiotic

  18. Macrophages and dendritic cells emerge in the liver during intestinal inflammation and predispose the liver to inflammation.

    Directory of Open Access Journals (Sweden)

    Yohei Mikami

    Full Text Available The liver is a physiological site of immune tolerance, the breakdown of which induces immunity. Liver antigen-presenting cells may be involved in both immune tolerance and activation. Although inflammatory diseases of the liver are frequently associated with inflammatory bowel diseases, the underlying immunological mechanisms remain to be elucidated. Here we report two murine models of inflammatory bowel disease: RAG-2(-/- mice adoptively transferred with CD4(+CD45RB(high T cells; and IL-10(-/- mice, accompanied by the infiltration of mononuclear cells in the liver. Notably, CD11b(-CD11c(lowPDCA-1(+ plasmacytoid dendritic cells (DCs abundantly residing in the liver of normal wild-type mice disappeared in colitic CD4(+CD45RB(high T cell-transferred RAG-2(-/- mice and IL-10(-/- mice in parallel with the emergence of macrophages (Mφs and conventional DCs (cDCs. Furthermore, liver Mφ/cDCs emerging during intestinal inflammation not only promote the proliferation of naïve CD4(+ T cells, but also instruct them to differentiate into IFN-γ-producing Th1 cells in vitro. The emergence of pathological Mφ/cDCs in the liver also occurred in a model of acute dextran sulfate sodium (DSS-induced colitis under specific pathogen-free conditions, but was canceled in germ-free conditions. Last, the Mφ/cDCs that emerged in acute DSS colitis significantly exacerbated Fas-mediated hepatitis. Collectively, intestinal inflammation skews the composition of antigen-presenting cells in the liver through signaling from commensal bacteria and predisposes the liver to inflammation.

  19. Introducing enteral feeding induces intestinal subclinical inflammation and respective chromatin changes in preterm pigs

    DEFF Research Database (Denmark)

    Willems, Rhea; Krych, Lukasz; Rybicki, Verena

    2015-01-01

    AIM: To analyze how enteral food introduction affects intestinal gene regulation and chromatin structure in preterm pigs. MATERIALS & METHODS: Preterm pigs were fed parenteral nutrition plus/minus slowly increasing volumes of enteral nutrition. Intestinal gene-expression and chromatin structure...... were analyzed 5 days after birth. RESULTS: Enteral feeding led to differential upregulation of inflammatory and pattern recognition receptor genes, including IL8 (median: 5.8, 95% CI: 3.9-7.8 for formula; median: 2.2, 95% CI: 1.3-3.3 for colostrum) and TLR4 (median: 3.7, 95% CI: 2.6-4.8 for formula...... stimulation with lipopolysaccharide (median: 7.0; interquartile range: 5.63-8.85) compared with naive cells (median 4.2; interquartile range: 2.45-6.33; p = 0.03). CONCLUSION: Enteral feeding, particular with formula, induces subclinical inflammation in the premature intestine and more open chromatin...

  20. Mortality in children with complicated severe acute malnutrition is related to intestinal and systemic inflammation: an observational cohort study

    NARCIS (Netherlands)

    Attia, Suzanna; Versloot, Christian J.; Voskuijl, Wieger; van Vliet, Sara J.; Di Giovanni, Valeria; Zhang, Ling; Richardson, Susan; Bourdon, Céline; Netea, Mihai G.; Berkley, James A.; van Rheenen, Patrick F.; Bandsma, Robert Hj

    2016-01-01

    Diarrhea affects a large proportion of children with severe acute malnutrition (SAM). However, its etiology and clinical consequences remain unclear. We investigated diarrhea, enteropathogens, and systemic and intestinal inflammation for their interrelation and their associations with mortality in

  1. Mortality in children with complicated severe acute malnutrition is related to intestinal and systemic inflammation : an observational cohort study

    NARCIS (Netherlands)

    Attia, Suzanna; Versloot, Christian J.; Voskuijl, Wieger; van Vliet, Sara J.; Di Giovanni, Valeria; Zhang, Ling; Richardson, Susan; Bourdon, Celine; Netea, Mihai G.; Berkley, James A.; van Rheenen, Patrick F.; Bandsma, Robert H. J.

    2016-01-01

    Background: Diarrhea affects a large proportion of children with severe acute malnutrition (SAM). However, its etiology and clinical consequences remain unclear. Objective: We investigated diarrhea, enteropathogens, and systemic and intestinal inflammation for their interrelation and their

  2. Mortality in children with complicated severe acute malnutrition is related to intestinal and systemic inflammation: an observational cohort study

    NARCIS (Netherlands)

    Attia, S.; Versloot, C.J.; Voskuijl, W.; Vliet, S.J. van; Giovanni, V. Di; Zhang, L.; Richardson, S.; Bourdon, C.; Netea, M.G.; Berkley, J.A.; Rheenen, P.F. van; Bandsma, R.H.

    2016-01-01

    BACKGROUND: Diarrhea affects a large proportion of children with severe acute malnutrition (SAM). However, its etiology and clinical consequences remain unclear. OBJECTIVE: We investigated diarrhea, enteropathogens, and systemic and intestinal inflammation for their interrelation and their

  3. Salmonella enterica serovar Typhimurium exploits inflammation to modify swine intestinal microbiota.

    Directory of Open Access Journals (Sweden)

    Rosanna eDrumo

    2016-01-01

    Full Text Available Salmonella enterica serovar Typhimurium is an important zoonotic gastrointestinal pathogen responsible for foodborne disease worldwide. It is a successful enteric pathogen because it has developed virulence strategies allowing it to survive in a highly inflamed intestinal environment exploiting inflammation to overcome colonization resistance provided by intestinal microbiota. In this study, we used piglets featuring an intact microbiota, which naturally develop gastroenteritis, as model for salmonellosis. We compared the effects on the intestinal microbiota induced by a wild type and an attenuated S. Typhimurium in order to evaluate whether the modifications are correlated with the virulence of the strain. This study showed that Salmonella alters microbiota in a virulence-dependent manner. We found that the wild type S. Typhimurium induced inflammation and a reduction of specific protecting microbiota species (SCFA-producing bacteria normally involved in providing a barrier against pathogens. Both these effects could contribute to impair colonization resistance, increasing the host susceptibility to wild type S. Typhimurium colonization. In contrast, the attenuated S. Typhimurium, which is characterized by a reduced ability to colonize the intestine, and by a very mild inflammatory response, was unable to successfully sustain competition with the microbiota.

  4. A Novel Pregabalin Functionalized Salicylaldehyde Derivative Afforded Prospective Pain, Inflammation, and Pyrexia Alleviating Propensities.

    Science.gov (United States)

    Ahmad, Nisar; Subhan, Fazal; Islam, Nazar Ul; Shahid, Muhammad; Rahman, Faiz Ur; Fawad, Khwaja

    2017-06-01

    A novel pregabalin derivative named as pregsal ((S,E)-3-(((2-hydroxybenzylidene)amino)methyl)-5-methylhexanoic acid) was synthesized by a simple imination reaction between pregabalin and salicylaldehyde and was evaluated in the in vivo testing paradigms. The compound was characterized by UV, IR, 1 H, 13 C NMR, HR ESI-MS, and elemental analysis. It was screened (30, 50, 75, and 100 mg/kg) for antinociceptive, anti-inflammatory, and antipyretic activities in relation to pregabalin. The synthesized compound significantly attenuated the tonic acetic acid-induced nociceptive pain (30 mg/kg (P pain, inflammation, and pyrexia relieving propensities and therefore may serve as a potential drug candidate for the therapeutic management of chronic pain conditions. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Titanium dioxide induced inflammation in the small intestine.

    Science.gov (United States)

    Nogueira, Carolina Maciel; de Azevedo, Walter Mendes; Dagli, Maria Lucia Zaidan; Toma, Sérgio Hiroshi; Leite, André Zonetti de Arruda; Lordello, Maria Laura; Nishitokukado, Iêda; Ortiz-Agostinho, Carmen Lúcia; Duarte, Maria Irma Seixas; Ferreira, Marcelo Alves; Sipahi, Aytan Miranda

    2012-09-14

    To investigate the effects of titanium dioxide (TiO₂) nanoparticles (NPTiO₂) and microparticles (MPTiO₂) on the inflammatory response in the small intestine of mice. Bl 57/6 male mice received distilled water suspensions containing TiO₂ (100 mg/kg body weight) as NPTiO₂ (66 nm), or MPTiO₂ (260 nm) by gavage for 10 d, once a day; the control group received only distilled water. At the end of the treatment the duodenum, jejunum and ileum were extracted for assessment of cytokines, inflammatory cells and titanium content. The cytokines interleukin (IL)-1b, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, IL-17, IL-23, tumor necrosis factor-α (TNF-α), intracellular interferon-γ (IFN-γ) and transforming growth factor-β (TGF-β) were evaluated by enzyme-linked immunosorbent assay in segments of jejunum and ileum (mucosa and underlying muscular tissue). CD4+ and CD8+ T cells, natural killer cells, and dendritic cells were evaluated in duodenum, jejunum and ileum samples fixed in 10% formalin by immunohistochemistry. The titanium content was determined by inductively coupled plasma atomic emission spectrometry. We found increased levels of T CD4+ cells (cells/mm²) in duodenum: NP 1240 ± 139.4, MP 1070 ± 154.7 vs 458 ± 50.39 (P NP 908.4 ± 130.3, MP 813.8 ± 103.8 vs 526.6 ± 61.43 (P NP 818.60 ± 123.0, MP 640.1 ± 32.75 vs 466.9 ± 22.4 (P NP 33.98 ± 11.76, MP 74.11 ± 25.65 vs 19.06 ± 3.92 (P NP 17.36 ± 9.96, MP 22.94 ± 7.47 vs 2.19 ± 0.65 (P NP 157.20 ± 75.80, MP 134.50 ± 38.31 vs 22.34 ± 5.81 (P NP 3.71 ± 1.33, MP 5.44 ± 1.67 vs 0.99 ± 019 (P NP 15.85 ± 9.99, MP 34.08 ± 11.44 vs 2.81 ± 0.69 (P NP 780.70 ± 318.50, MP 1409.00 ± 502.20 vs 205.50 ± 63.93 (P < 0.05). Our findings indicate that TiO₂ particles induce a Th1-mediated inflammatory response in the small bowel in mice.

  6. Titanium dioxide induced inflammation in the small intestine

    Science.gov (United States)

    Nogueira, Carolina Maciel; de Azevedo, Walter Mendes; Dagli, Maria Lucia Zaidan; Toma, Sérgio Hiroshi; Leite, André Zonetti de Arruda; Lordello, Maria Laura; Nishitokukado, Iêda; Ortiz-Agostinho, Carmen Lúcia; Duarte, Maria Irma Seixas; Ferreira, Marcelo Alves; Sipahi, Aytan Miranda

    2012-01-01

    AIM: To investigate the effects of titanium dioxide (TiO2) nanoparticles (NPTiO2) and microparticles (MPTiO2) on the inflammatory response in the small intestine of mice. METHODS: Bl 57/6 male mice received distilled water suspensions containing TiO2 (100 mg/kg body weight) as NPTiO2 (66 nm), or MPTiO2 (260 nm) by gavage for 10 d, once a day; the control group received only distilled water. At the end of the treatment the duodenum, jejunum and ileum were extracted for assessment of cytokines, inflammatory cells and titanium content. The cytokines interleukin (IL)-1b, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, IL-17, IL-23, tumor necrosis factor-α (TNF-α), intracellular interferon-γ (IFN-γ) and transforming growth factor-β (TGF-β) were evaluated by enzyme-linked immunosorbent assay in segments of jejunum and ileum (mucosa and underlying muscular tissue). CD4+ and CD8+ T cells, natural killer cells, and dendritic cells were evaluated in duodenum, jejunum and ileum samples fixed in 10% formalin by immunohistochemistry. The titanium content was determined by inductively coupled plasma atomic emission spectrometry. RESULTS: We found increased levels of T CD4+ cells (cells/mm2) in duodenum: NP 1240 ± 139.4, MP 1070 ± 154.7 vs 458 ± 50.39 (P < 0.01); jejunum: NP 908.4 ± 130.3, MP 813.8 ± 103.8 vs 526.6 ± 61.43 (P < 0.05); and ileum: NP 818.60 ± 123.0, MP 640.1 ± 32.75 vs 466.9 ± 22.4 (P < 0.05). In comparison to the control group, the groups receiving TiO2 showed a statistically significant increase in the levels of the inflammatory cytokines IL-12, IL-4, IL-23, TNF-α, IFN-γ and TGF-β. The cytokine production was more pronounced in the ileum (mean ± SE): IL-12: NP 33.98 ± 11.76, MP 74.11 ± 25.65 vs 19.06 ± 3.92 (P < 0.05); IL-4: NP 17.36 ± 9.96, MP 22.94 ± 7.47 vs 2.19 ± 0.65 (P < 0.05); IL-23: NP 157.20 ± 75.80, MP 134.50 ± 38.31 vs 22.34 ± 5.81 (P < 0.05); TNFα: NP 3.71 ± 1.33, MP 5.44 ± 1.67 vs 0.99 ± 019 (P < 0.05); IFNγ: NP 15.85 ± 9

  7. Selective phosphodiesterase-2A inhibitor alleviates radicular inflammation and mechanical allodynia in non-compressive lumbar disc herniation rats.

    Science.gov (United States)

    Wang, Jun-Nan; Zhao, Xue-Jun; Liu, Zhi-Hua; Zhao, Xu-Li; Sun, Tao; Fu, Zhi-Jian

    2017-07-01

    Phosphodiesterase inhibitors possess anti-inflammatory properties. In addition, some studies report that phosphodiesterase 2A (PDE2A) are highly expressed in the dorsal horn of the spinal cord. The present study aimed to investigate whether intrathecal administration of Bay 60-7550, a specific PDE2A inhibitor, could alleviate mechanical allodynia in non-compressive lumbar disc herniation (NCLDH) rats. Rat NCLDH models by autologous nucleus pulposus implantation to dorsal root ganglion were established. Vehicle or Bay 60-7550 (0.1, 1.0 mg/kg) was injected by intrathecal catheter at day 1 post-operation. The ipsilateral mechanical withdrawal thresholds were analyzed from the day before surgery to day 7 after surgery. At day 7 post-operation, the ipsilateral lumbar (L4-L6) segments of the spinal dorsal horns were removed, and tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), cyclic adenosine monophosphate (cAMP), and cyclic guanosine monophosphate (cGMP) expressions were measured by ELISA. Furthermore, PDE2A mRNA and protein expressions in spinal cord were measured by Real-Time PCR and Western blot. Intrathecal administration of the PDE2A inhibitor Bay 60-7550, significantly attenuated mechanical allodynia, down-regulated spinal TNF-α, IL-1β and IL-6 over-expressions, increased the expression of spinal cAMP, as well as cGMP in a more remarkable manner, and decreased the spinal PDE2A expression in NCLDH rats in a dose-dependent manner. Bay 60-7550 alleviated mechanical allodynia and inflammation in NCLDH rats, which might be associated with increased cAMP and especially cGMP increase. Thus, spinal PDE2A inhibition might represent a potential analgesic strategy for radiculopathy treatment in non-compressive lumbar disc herniation.

  8. HemoHIM, a herbal preparation, alleviates airway inflammation caused by cigarette smoke and lipopolysaccharide.

    Science.gov (United States)

    Shin, Na-Rae; Kim, Sung-Ho; Ko, Je-Won; Park, Sung-Hyeuk; Lee, In-Chul; Ryu, Jung-Min; Kim, Jong-Choon; Shin, In-Sik

    2017-03-01

    HemoHIM, herbal preparation has designed for immune system recovery. We investigated the anti-inflammatory effect of HemoHIM on cigarette smoke (CS) and lipopolysaccharide (LPS) induced chronic obstructive pulmonary disease (COPD) mouse model. To induce COPD, C57BL/6 mice were exposed to CS for 1 h per day (eight cigarettes per day) for 4 weeks and intranasally received LPS on day 26. HemoHIM was administrated to mice at a dose of 50 or 100 mg/kg 1h before CS exposure. HemoHIM reduced the inflammatory cell count and levels of tumor necrosis factor receptor (TNF)-α, interleukin (IL)-6 and IL-1β in the broncho-alveolar lavage fluid (BALF) induced by CS+LPS exposure. HemoHIM decreased the inflammatory cell infiltration in the airway and inhibited the expression of iNOS and MMP-9 and phosphorylation of Erk in lung tissue exposed to CS+LPS. In summary, our results indicate that HemoHIM inhibited a reduction in the lung inflammatory response on CS and LPS induced lung inflammation via the Erk pathway. Therefore, we suggest that HemoHIM has the potential to treat pulmonary inflammatory disease such as COPD.

  9. Purinergic Ligands as Potential Therapeutic Tools for the Treatment of Inflammation-Related Intestinal Diseases

    Directory of Open Access Journals (Sweden)

    Diego Dal Ben

    2018-03-01

    Full Text Available Inflammation-related intestinal diseases are a set of various conditions presenting an overactive enteric immune system. A continuous overproduction of pro-inflammatory cytokines and a decreased production of anti-inflammatory modulators are generally observed, while morpho-functional alterations of the enteric nervous system lead to intestinal secretory and motor dysfunctions. The factors at the basis of these conditions are still to be totally identified and current therapeutic strategies are aimed only at achieving and maintaining remission states, by using therapeutic tools like aminosalicylates, corticosteroids, immunomodulators, biological drugs (i.e., monoclonal antibodies, and eventually surgery. Recent reports described a key role of purinergic mediators (i.e., adenosine and its nucleotides ATP and ADP in the regulation of the activity of immune cells and enteric nervous system, showing also that alterations of the purinergic signaling are linked to pathological conditions of the intestinal tract. These data prompted to a series of investigations to test the therapeutic potential for inflammation-related intestinal conditions of compounds able to restore or modulate an altered purinergic signaling within the gut. This review provides an overview on these investigations, describing the results of preclinical and/or clinical evaluation of compounds able to stimulate or inhibit specific P2 (i.e., P2X7 or P1 (i.e., A2A or A3 receptor signaling and to modify the adenosine levels through the modulation of enzymes activity (i.e., Adenosine Deaminase or nucleoside transporters. Recent developments in the field are also reported and the most promising purine-based therapeutic strategies for the treatment of inflammation-related gastrointestinal disorders are schematically summarized.

  10. Characterization and pharmacological modulation of intestinal inflammation induced by ionizing radiation

    International Nuclear Information System (INIS)

    Gremy, O.

    2006-12-01

    The use of radiation therapy to treat abdominal and pelvic malignancies inevitably involves exposure of healthy intestinal tissues which are very radiosensitive. As a result, most patients experience symptoms such as abdominal pain, nausea and diarrhea. Such symptoms are associated with acute damage to intestine mucosa including radio-induced inflammatory processes. With a rat model of colorectal fractionated radiation, we have shown a gradual development of a colonic inflammation during radiation planning, without evident tissue injury. This radio-induced inflammation is characterized not only by the sur expressions of pro-inflammatory cytokines and chemokines, a NF-kB activation, but also by a repression of anti-inflammatory cytokines and the nuclear receptors PPARa and RXRa, both involved in inflammation control. This early inflammation is associated with a discreet neutrophil recruitment and a macrophage accumulation. Macrophages are still abnormally numerous in tissue 27 weeks after the last day of irradiation. Inflammatory process is the most often related to a specific immune profile, either a type Th1 leading to a cellular immune response, or a type Th2 for humoral immunity. According to our studies, a unique abdominal radiation in the rat induces an ileum inflammation and an immune imbalance resulting in a Th2-type profile. Inhibiting this profile is important as its persistence promotes chronic inflammation, predisposition to bacterial infections and fibrosis which is the main delayed side-effect of radiotherapy. The treatment of rats with an immuno-modulator compound, the caffeic acid phenethyl ester (C.A.P.E.), have the potential to both reduce ileal mucosal inflammation and inhibit the radio-induced Th2 status. In order to search new therapeutic molecular target, we has been interested in the PPARg nuclear receptor involved in the maintenance of colon mucosal integrity. In our abdominal irradiation model, we have demonstrated that the prophylactic

  11. Ciprofloxacin blocked enterohepatic circulation of diclofenac and alleviated NSAID-induced enteropathy in rats partly by inhibiting intestinal β-glucuronidase activity.

    Science.gov (United States)

    Zhong, Ze-Yu; Sun, Bin-Bin; Shu, Nan; Xie, Qiu-Shi; Tang, Xian-Ge; Ling, Zhao-Li; Wang, Fan; Zhao, Kai-Jing; Xu, Ping; Zhang, Mian; Li, Ying; Chen, Yang; Liu, Li; Xia, Lun-Zhu; Liu, Xiao-Dong

    2016-07-01

    Diclofenac is a non-steroidal anti-inflammatory drug (NSAID), which may cause serious intestinal adverse reactions (enteropathy). In this study we investigated whether co-administration of ciprofloxacin affected the pharmacokinetics of diclofenac and diclofenac-induced enteropathy in rats. The pharmacokinetics of diclofenac was assessed in rats after receiving diclofenac (10 mg/kg, ig, or 5 mg/kg, iv), with or without ciprofloxacin (20 mg/kg, ig) co-administered. After receiving 6 oral doses or 15 intravenous doses of diclofenac, the rats were sacrificed, and small intestine was removed to examine diclofenac-induced enteropathy. β-Glucuronidase activity in intestinal content, bovine liver and E coli was evaluated. Following oral or intravenous administration, the pharmacokinetic profile of diclofenac displayed typical enterohepatic circulation, and co-administration of ciprofloxacin abolished the enterohepatic circulation, resulted in significant reduction in the plasma content of diclofenac. In control rats, β-glucuronidase activity in small intestinal content was region-dependent: proximal intestinediclofenac, typical enteropathy was developed with severe enteropathy occurred in distal small intestine. Co-administration of ciprofloxacin significantly alleviated diclofenac-induced enteropathy. Co-administration of ciprofloxacin attenuated enterohepatic circulation of diclofenac and alleviated diclofenac-induced enteropathy in rats, partly via the inhibition of intestinal β-glucuronidase activity.

  12. Ciprofloxacin blocked enterohepatic circulation of diclofenac and alleviated NSAID-induced enteropathy in rats partly by inhibiting intestinal β-glucuronidase activity

    Science.gov (United States)

    Zhong, Ze-yu; Sun, Bin-bin; Shu, Nan; Xie, Qiu-shi; Tang, Xian-ge; Ling, Zhao-li; Wang, Fan; Zhao, Kai-jing; Xu, Ping; Zhang, Mian; Li, Ying; Chen, Yang; Liu, Li; Xia, Lun-zhu; Liu, Xiao-dong

    2016-01-01

    Aim: Diclofenac is a non-steroidal anti-inflammatory drug (NSAID), which may cause serious intestinal adverse reactions (enteropathy). In this study we investigated whether co-administration of ciprofloxacin affected the pharmacokinetics of diclofenac and diclofenac-induced enteropathy in rats. Methods: The pharmacokinetics of diclofenac was assessed in rats after receiving diclofenac (10 mg/kg, ig, or 5 mg/kg, iv), with or without ciprofloxacin (20 mg/kg, ig) co-administered. After receiving 6 oral doses or 15 intravenous doses of diclofenac, the rats were sacrificed, and small intestine was removed to examine diclofenac-induced enteropathy. β-Glucuronidase activity in intestinal content, bovine liver and E coli was evaluated. Results: Following oral or intravenous administration, the pharmacokinetic profile of diclofenac displayed typical enterohepatic circulation, and co-administration of ciprofloxacin abolished the enterohepatic circulation, resulted in significant reduction in the plasma content of diclofenac. In control rats, β-glucuronidase activity in small intestinal content was region-dependent: proximal intestinediclofenac, typical enteropathy was developed with severe enteropathy occurred in distal small intestine. Co-administration of ciprofloxacin significantly alleviated diclofenac-induced enteropathy. Conclusion: Co-administration of ciprofloxacin attenuated enterohepatic circulation of diclofenac and alleviated diclofenac-induced enteropathy in rats, partly via the inhibition of intestinal β-glucuronidase activity. PMID:27180979

  13. Endothelial targeting of liposomes encapsulating SOD/catalase mimetic EUK-134 alleviates acute pulmonary inflammation.

    Science.gov (United States)

    Howard, Melissa D; Greineder, Colin F; Hood, Elizabeth D; Muzykantov, Vladimir R

    2014-03-10

    Production of excessive levels of reactive oxygen species (ROS) in the vascular endothelium is a common pathogenic pathway in many dangerous conditions, including acute lung injury, ischemia-reperfusion, and inflammation. Ineffective delivery of antioxidants to the endothelium limits their utility for management of these conditions. In this study, we devised a novel translational antioxidant intervention targeted to the vascular endothelium using PEG-liposomes loaded with EUK-134 (EUK), a potent superoxide dismutase/catalase mimetic. EUK loaded into antibody-coated liposomes (size 197.8±4.5 nm diameter, PDI 0.179±0.066) exerted partial activity in the intact carrier, while full activity was recovered upon liposome disruption. For targeting we used antibodies (Abs) to platelet-endothelial cell adhesion molecule (PECAM-1). Both streptavidin-biotin and SATA/SMCC conjugation chemistries provided binding of 125-150 Ab molecules per liposome. Ab/EUK/liposomes, but not IgG/EUK/liposomes: i) bound to endothelial cells and inhibited cytokine-induced inflammatory activation in vitro; and, ii) accumulated in lungs after intravascular injection, providing >60% protection against pulmonary edema in endotoxin-challenged mice (vs <6% protection afforded by IgG/liposome/EUK counterpart). Since the design elements of this drug delivery system are already in clinical use (PEG-liposomes, antibodies, SATA/SMCC conjugation), it is an attractive candidate for translational interventions using antioxidant molecules such as EUK and other clinically acceptable drugs. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Activation of Epac alleviates inflammation and vascular leakage in LPS-induced acute murine lung injury.

    Science.gov (United States)

    Wang, Xuefeng; Song, Shunde; Hu, Zhengqiang; Zhang, Zhewen; Li, Yajun; Yan, Chunguang; Li, Zigang; Tang, Huifang

    2017-12-01

    Exchange protein directly activated by cAMP (Epac) is an important molecule in cAMP signal transduction, but the effect of Epac on lipopolysaccharide (LPS)-induced acute lung injury (ALI) is unclear. In this study, we treated in vitro and in vivo models with the Epac activator 8CPT to determine the effect and related mechanisms of Epac. The in vitro results indicate that 8CPT inhibits lipopolysaccharide (LPS)-induced tumor necrosis factor-α (TNF-α) release from mouse macrophages (MH-S), whereas the protein kinase A (PKA) activator 6BnZ has no effect. Furthermore, Epac over-expression can significantly suppress TNF-α release from LPS induced MH-S cell, while Epac siRNA can slightly increase TNF-α release. Moreover, 8CPT reduces LPS-induced microvascular permeability in human pulmonary microvascular endothelial cells (HPMVECs), whereas the PKA activator 6BnZ has no effect. In mice with LPS-induced ALI, 8CPT significantly reduces LPS-induced inflammatory cytokine release, neutrophil recruitment, and albumin leakage. LPS simultaneously decreases the Epac but not the PKA levels. However, 8CPT reverses the decreased Epac levels. Furthermore, the mechanism involves the small GTPase Rac1/2 but not the mitogen-activated protein kinase (MAPK) pathway. Thus, Epac activation reduces inflammation and microvascular permeability in LPS-induced lung injury and an Epac activator represents a novel choice for the early therapy of ALI. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  15. Ganoderma Triterpenoids Exert Antiatherogenic Effects in Mice by Alleviating Disturbed Flow-Induced Oxidative Stress and Inflammation

    Directory of Open Access Journals (Sweden)

    Pei-Ling Hsu

    2018-01-01

    Full Text Available Ganoderma mushrooms, used in traditional Chinese medicine to promote health and longevity, have become widely accepted as herbal supplements. Ganoderma lucidum (GL, a commonly seen ganoderma species, is commercially cultivated under controlled conditions for more consistent chemical composition. The medicinal properties of GL are attributable to its antioxidant and anti-inflammatory activities. We intended to assess the effect of GL in atherosclerosis, an arterial condition associated with chronic oxidative stress and inflammation, using a carotid-artery-ligation mouse model. Flow turbulence created in the ligated artery induces oxidative stress and neointimal hyperplasia, a feature of early atherogenesis. Daily oral GL prevented neointimal thickening 2 weeks after ligation. Moreover, the ganoderma triterpenoid (GT crude extract isolated from GL abolished ligation-induced neointima formation. Mechanistically, endothelial dysfunction was observed 3 days after ligation before any structural changes could be detected. GTs alleviated the oxidative stress and restored the atheroresistent status of endothelium by inhibiting the induction of a series of atherogenic factors, including endothelin-1, von Willebrand factor, and monocyte chemoattractant protein-1 after 3-day ligation. The anti-inflammatory activity of GTs was tested in cultured human umbilical vein endothelial cells (HUVECs exposed to disturbed flow in an in vitro perfusion system. GTs abolished the induction of proinflammatory VCAM-1, TNF-α, and IL-6 by oscillatory shear stress. Moreover, the antioxidant activity of GTs was tested in HUVECs against the insult of H2O2. GTs dissipated the cellular superoxide accumulation imposed by H2O2, thereby mitigating H2O2-induced cell damage and proatherogenic response. Our results revealed the atheroprotective properties of ganoderma mushrooms and identified triterpenoids as the critical constituents for those effects. GTs prevent atherogenesis by

  16. Dietary Bacillus subtilis-based direct-fed microbials alleviate LPS-induced intestinal immunological stress and improve intestinal barrier gene expression in commercial broiler chickens.

    Science.gov (United States)

    Gadde, Ujvala Deepthi; Oh, Sungtaek; Lee, Youngsub; Davis, Ellen; Zimmerman, Noah; Rehberger, Tom; Lillehoj, Hyun Soon

    2017-10-01

    This study investigated the effects of Bacillus subtilis-based probiotics on the performance, modulation of host inflammatory responses and intestinal barrier gene expression of broilers subjected to LPS challenge. Chickens were randomly allocated to one of the 3 dietary treatment groups - control, antibiotic, or probiotic. At 14days, half of the chickens in each treatment were injected with LPS (1mg/kg body weight), and the other half injected with sterile PBS. Chickens fed probiotics weighed significantly more than controls at 15days of age, irrespective of immune challenge. LPS challenge significantly reduced weight gain at 24h post-injection, and the probiotics did not alleviate the LPS-induced reduction of weight gain. Serum α-1-AGP levels were significantly higher in LPS-injected chickens, and probiotic supplementation significantly reduced their levels. The percentages of CD4+ lymphocytes were significantly increased in probiotic groups in the absence of immunological challenge but were reduced during LPS challenge compared to controls. CD8+ lymphocytes were significantly reduced in probiotic-fed birds. The LPS-induced increase in the expression of cytokines IL8 and TNFSF15 was reduced by probiotic supplementation, and IL17F, iNOS expression was found to be significantly elevated in probiotic-fed birds subjected to LPS challenge. The reduced gene expression of tight junction proteins (JAM2, occludin and ZO1) and MUC2 induced by LPS challenge was reversed by probiotic supplementation. The results indicate that B. subtilis-based probiotics differentially regulate intestinal immune and tight junction protein mRNA expression during states of LPS-mediated immunological challenge. Published by Elsevier Ltd.

  17. Effect of microalgae on intestinal inflammation triggered by soybean meal and bacterial infection in zebrafish.

    Directory of Open Access Journals (Sweden)

    Karina Bravo-Tello

    Full Text Available Soybean meal has been used in many commercial diets for farm fish; despite this component inducing intestinal inflammation. On the other hand, microalgae have increasingly been used as dietary supplements in fish feed. Nevertheless, the vast quantity of microalgae species means that many remain under- or unstudied, thus limiting wide scale commercial application. In this work, we evaluated the effects to zebrafish (Danio rerio of including Tetraselmis sp (Ts; Phaeodactylum tricornutum (Pt; Chlorella sp (Ch; Nannochloropsis oculata (No; or Nannochloropsis gaditana (Ng as additives in a soybean meal-based diet on intestinal inflammation and survival after Edwardsiella tarda infection. In larvae fed a soybean meal diet supplemented with Ts, Pt, Ch, or Ng, the quantity of neutrophils present in the intestine drastically decreased as compared to larvae fed only the soybean meal diet. Likewise, Ts or Ch supplements in soybean meal or fishmeal increased zebrafish survival by more than 20% after being challenged. In the case of Ts, the observed effect correlated with an increased number of neutrophils present at the infection site. These results suggest that the inclusion of Ts or Ch in fish diets could allow the use of SBM and at the same time improve performance against pathogen.

  18. Effect of microalgae on intestinal inflammation triggered by soybean meal and bacterial infection in zebrafish

    Science.gov (United States)

    Solís, Camila J.; Ulloa, Pilar E.; Hedrera, Manuel; Pizarro-Guajardo, Marjorie; Paredes-Sabja, Daniel

    2017-01-01

    Soybean meal has been used in many commercial diets for farm fish; despite this component inducing intestinal inflammation. On the other hand, microalgae have increasingly been used as dietary supplements in fish feed. Nevertheless, the vast quantity of microalgae species means that many remain under- or unstudied, thus limiting wide scale commercial application. In this work, we evaluated the effects to zebrafish (Danio rerio) of including Tetraselmis sp (Ts); Phaeodactylum tricornutum (Pt); Chlorella sp (Ch); Nannochloropsis oculata (No); or Nannochloropsis gaditana (Ng) as additives in a soybean meal-based diet on intestinal inflammation and survival after Edwardsiella tarda infection. In larvae fed a soybean meal diet supplemented with Ts, Pt, Ch, or Ng, the quantity of neutrophils present in the intestine drastically decreased as compared to larvae fed only the soybean meal diet. Likewise, Ts or Ch supplements in soybean meal or fishmeal increased zebrafish survival by more than 20% after being challenged. In the case of Ts, the observed effect correlated with an increased number of neutrophils present at the infection site. These results suggest that the inclusion of Ts or Ch in fish diets could allow the use of SBM and at the same time improve performance against pathogen. PMID:29117213

  19. Liver Inflammation Relates to Decreased Canalicular Bile Transporter Expression in Pediatric Onset Intestinal Failure.

    Science.gov (United States)

    Mutanen, Annika; Lohi, Jouko; Heikkilä, Päivi; Jalanko, Hannu; Pakarinen, Mikko P

    2017-02-23

    Although liver disease is a major complication of parenteral nutrition (PN) for intestinal failure (IF), its pathogenesis remains unclear. We investigated potential molecular mechanisms of liver injury in pediatric onset IF. Liver expression of canalicular phospholipid (ABCB4), bile acid (ABCB11), and sterol (ABCG5/8) transporters, their upstream regulators LXR and FXR as well as pro-inflammatory cytokines interleukin-6 (IL6) and tumor necrosis factor (TNF) were investigated among patients with IF [age median 3.8 (IQR 1.2 to 11)] in relation to biochemical and histologic liver injury, PN, serum plant sterols, fibroblast growth factor 19, and α-tocopherol. Patients receiving PN currently (n = 18) showed more advanced liver injury than patients after weaning off PN (n = 30). Histologic portal inflammation strongly segregated PN-dependent (44%) from weaned off patients (3%, P = 0.001) and coupled with progression of cholestasis and liver fibrosis. Patients with portal inflammation demonstrated markedly induced liver RNA expression of IL6 and TNF, repression of FXR and its canalicular bile transporter target gene RNA expression, including ABCB4 and ABCB11 as well as decreased protein expression of ABCB11 and ABCB4. Furthermore, upregulation of LXR and ABCG5/8 RNA expression was suppressed in patients with portal inflammation. Current PN, increased serum levels of plant sterols stigmasterol, avenasterol, and sitosterol along with serum citrulline, a marker of enterocyte mass, predicted portal inflammation. In pediatric onset IF, current PN delivery synergistically with intestinal compromise promote liver inflammation, which associates with progression of biochemical and histologic liver injury, while reducing expression of canalicular bile transporters.

  20. 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. PMID:29416538

  1. miR-200bc/429 cluster alleviates inflammation in IgA nephropathy by targeting TWEAK/Fn14.

    Science.gov (United States)

    Guo, Yong; Liao, Yuanjiang

    2017-11-01

    Immunoglobulin A nephropathy (IgAN) is one of the most common glomerular diseases worldwide. Various studies have identified a host of microRNAs (miRNAs) abnormally expressed in IgAN and might affect the pathogenesis and progression of IgAN. However, miR-200bc/429 cluster in the pathopoiesis of IgAN remains poorly understood. For this study, we found that miR-200bc/429 cluster is downregulated in IgAN tissues and IgAN podocytes and HK2 cells compared with their matched controls respectively. In addition, overexpression of miR-200bc/429 cluster in IgAN podocytes and HK2 cells could attenuate the release of inflammatory cytokines MCP-1, IL-6 and RANTES. Moreover, the 3' untranslated region (UTR) of TNF-like weak inducer of apoptosis (TWEAK) was identified to be a direct target of miR-200bc/429 cluster. Furthermore, our results showed that miR-200bc/429 cluster can inhibit TWEAK mediated NF-κB pathway activation in IgAN. Overall, our findings revealed that miR-200bc/429 cluster alleviates inflammation in IgAN through TWEAK/Fn14 system and might serve as a biomarker as well as a promising therapeutic target for IgAN. Copyright © 2017. Published by Elsevier B.V.

  2. Mucosal innate immune cells regulate both gut homeostasis and intestinal inflammation.

    Science.gov (United States)

    Kurashima, Yosuke; Goto, Yoshiyuki; Kiyono, Hiroshi

    2013-12-01

    Continuous exposure of intestinal mucosal surfaces to diverse microorganisms and their metabolites reflects the biological necessity for a multifaceted, integrated epithelial and immune cell-mediated regulatory system. The development and function of the host cells responsible for the barrier function of the intestinal surface (e.g., M cells, Paneth cells, goblet cells, and columnar epithelial cells) are strictly regulated through both positive and negative stimulation by the luminal microbiota. Stimulation by damage-associated molecular patterns and commensal bacteria-derived microbe-associated molecular patterns provokes the assembly of inflammasomes, which are involved in maintaining the integrity of the intestinal epithelium. Mucosal immune cells located beneath the epithelium play critical roles in regulating both the mucosal barrier and the relative composition of the luminal microbiota. Innate lymphoid cells and mast cells, in particular, orchestrate the mucosal regulatory system to create a mutually beneficial environment for both the host and the microbiota. Disruption of mucosal homeostasis causes intestinal inflammation such as that seen in inflammatory bowel disease. Here, we review the recent research on the biological interplay among the luminal microbiota, epithelial cells, and mucosal innate immune cells in both healthy and pathological conditions. © 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Dietary emulsifiers directly alter human microbiota composition and gene expression ex vivo potentiating intestinal inflammation.

    Science.gov (United States)

    Chassaing, Benoit; Van de Wiele, Tom; De Bodt, Jana; Marzorati, Massimo; Gewirtz, Andrew T

    2017-08-01

    The intestinal microbiota plays a central role in the development of many chronic inflammatory diseases including IBD and metabolic syndrome. Administration of substances that alter microbiota composition, including the synthetic dietary emulsifiers polysorbate 80 (P80) and carboxymethylcellulose (CMC), can promote such inflammatory disorders. However, that inflammation itself impacts microbiota composition has obfuscated defining the extent to which these compounds or other substances act directly upon the microbiota versus acting on host parameters that promote inflammation, which subsequently reshapes the microbiota. We examined the direct impact of CMC and P80 on the microbiota using the mucosal simulator of the human intestinal microbial ecosystem (M-SHIME) model that maintains a complex stable human microbiota in the absence of a live host. This approach revealed that both P80 and CMC acted directly upon human microbiota to increase its proinflammatory potential, as revealed by increased levels of bioactive flagellin. The CMC-induced increase in flagellin was rapid (1 day) and driven by altered microbiota gene expression. In contrast, the P80-induced flagellin increase occurred more slowly and was closely associated with altered species composition. Transfer of both emulsifier-treated M-SHIME microbiotas to germ-free recipient mice recapitulated many of the host and microbial alterations observed in mice directly treated with emulsifiers. These results demonstrate a novel paradigm of deconstructing host-microbiota interactions and indicate that the microbiota can be directly impacted by these commonly used food additives, in a manner that subsequently drives intestinal inflammation. 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/.

  4. Associations of cocaine use and HIV infection with the intestinal microbiota, microbial translocation, and inflammation.

    Science.gov (United States)

    Volpe, Gretchen E; Ward, Honorine; Mwamburi, Mkaya; Dinh, Duy; Bhalchandra, Seema; Wanke, Christine; Kane, Anne V

    2014-03-01

    HIV and illicit drug use have been associated with altered nutrition, immune function, and metabolism. We hypothesized that altered composition and decreased diversity of the intestinal microbiota, along with microbial translocation, contribute to nutritional compromise in HIV-infected drug users. We enrolled 26 men and 6 women, 15 HIV infected and 17 HIV uninfected, in this exploratory, cross-sectional study; 7 HIV-infected and 7 HIV-uninfected participants had used cocaine within the previous month. We examined the independent effects of cocaine use and HIV infection on the composition and diversity of the intestinal microbiota, determined by 16S rRNA gene pyrosequencing. Using dietary records, anthropometrics, and dual x-ray absorptiometry, we examined the additional effects of nutritional indices on the intestinal microbiota. We compared markers of inflammation and microbial translocation between groups. Cocaine users had a higher relative abundance of Bacteroidetes (M ± SD = 57.0% ± 21 vs. 37.1% ± 23, p = .02) than nonusers. HIV-infected individuals had a higher relative abundance of Proteobacteria (Mdn [interquartile range] = 1.56% [0.5, 2.2] vs. 0.36% [0.2, 0.7], p = .03), higher levels of soluble CD14 and tumor necrosis factor-α, and lower levels of anti-endotoxin core antibodies than uninfected subjects. HIV-infected cocaine users had higher interferon-γ levels than all other groups. Food insecurity was higher in HIV-infected cocaine users. We identified differences in the relative abundance of major phyla of the intestinal microbiota, as well as markers of inflammation and microbial translocation, based on cocaine use and HIV infection. Nutritional factors, including alcohol use and lean body mass, may contribute to these differences.

  5. MARKERS OF THE ENTERIC INFLAMMATION IN THE EVENT OF INTESTINAL DISEASES: LITERATURE REVIEW

    Directory of Open Access Journals (Sweden)

    O.F. Tat'yanina

    2008-01-01

    Full Text Available The authors provided modern information on the basic noninvasive methods to assess the inflammatory process in the intestine in crohn's disease and colitis gravis. The researchers thoroughly described the opportunities and limitations for the use of faecal calprotectin as a marker of the inflammatory enteric diseases. Importance of this marker for the differential diagnostics of  the inflammatory and functional enteric diseases has been shown.Key words: markers of the enteric inflammation, faecal calprotectin, inflammatory bowel diseases, colitis gravis, сrohn's disease.

  6. Fermented milk containing Lactobacillus GG alleviated DSS-induced colitis in mice and activated epidermal growth factor receptor and Akt signaling in intestinal epithelial cells

    Directory of Open Access Journals (Sweden)

    Kazutoyo Yoda

    2012-06-01

    Full Text Available Lactobacillus rhamnosus GG was assessed for its ability to alleviate DSS-induced colitis in mice and activate epidermal growth factor receptor and Akt signaling in intestinal epithelial cells. In this study mice were treated with DSS to induce colitis and they were given Lactobacillus GG fermented milk to assess the effect of probiotic on colitis. Lactobacillus GG fermented milk significantly reduced the colitis associated changes suggesting a protective effect against DSS induced colitis.

  7. Orally delivered thioketal nanoparticles loaded with TNF-α-siRNA target inflammation and inhibit gene expression in the intestines

    Science.gov (United States)

    Wilson, D. Scott; Dalmasso, Guillaume; Wang, Lixin; Sitaraman, Shanthi V.; Merlin, Didier; Murthy, Niren

    2010-11-01

    Small interfering RNAs (siRNAs) directed against proinflammatory cytokines have the potential to treat numerous diseases associated with intestinal inflammation; however, the side-effects caused by the systemic depletion of cytokines demands that the delivery of cytokine-targeted siRNAs be localized to diseased intestinal tissues. Although various delivery vehicles have been developed to orally deliver therapeutics to intestinal tissue, none of these strategies has demonstrated the ability to protect siRNA from the harsh environment of the gastrointestinal tract and target its delivery to inflamed intestinal tissue. Here, we present a delivery vehicle for siRNA, termed thioketal nanoparticles (TKNs), that can localize orally delivered siRNA to sites of intestinal inflammation, and thus inhibit gene expression in inflamed intestinal tissue. TKNs are formulated from a polymer, poly-(1,4-phenyleneacetone dimethylene thioketal), that degrades selectively in response to reactive oxygen species (ROS). Therefore, when delivered orally, TKNs release siRNA in response to the abnormally high levels of ROS specific to sites of intestinal inflammation. Using a murine model of ulcerative colitis, we demonstrate that orally administered TKNs loaded with siRNA against the proinflammatory cytokine tumour necrosis factor-alpha (TNF-α) diminish TNF-α messenger RNA levels in the colon and protect mice from ulcerative colitis.

  8. Dexmedetomidine Ameliorate CLP-Induced Rat Intestinal Injury via Inhibition of Inflammation.

    Science.gov (United States)

    Chen, Yanqing; Miao, Liyan; Yao, Yusheng; Wu, Weilan; Wu, Xiaodan; Gong, Cansheng; Qiu, Liangcheng; Chen, Jianping

    2015-01-01

    The aim was to verify that dexmedetomidine (DEX) can attenuate CLP-induced intestinal injury via inhibition of inflammation. Male Sprague-Dawley (SD) rats were randomly allocated into Sham group and the other three CLP model groups, in terms of different treatments: placebo, DEX, and yohimbine plus DEX (DEX + YOH) groups. Pathology examination was conducted with HE stain. To identify differences among groups, the levels of DAO, and D-lactate in serum were measured by spectrophotometry, and the levels of TNF-α, IL-1β, and IL-6 in serum and organ were measured by ELISA. The expressions of occludin and TLR4 in tissue were detected by Western blot. The survival rate of an additional group of animals within 7 d was recorded. In DEX group, mortality was lower, histology change was minor, DAO, and D-lactate levels were reduced, and occludin expression was increased; the expressions of TNF-α, IL-1β, IL-6, and TLR4 were also decreased in DEX group. These results indicated that acute intestinal injury induced by CLP was mitigated by DEX treatment. However, these effects of DEX were significantly attenuated by yohimbine in DEX + YOH group. Our study indicated the protective effects of DEX on CLP-induced injury, which may be associated with the inhibition of inflammation via modulating TLR4 pathway and can be blocked by yohimbine.

  9. Methylation of polycomb target genes in intestinal cancer is mediated by inflammation.

    Science.gov (United States)

    Hahn, Maria A; Hahn, Torsten; Lee, Dong-Hyun; Esworthy, R Steven; Kim, Byung-Wook; Riggs, Arthur D; Chu, Fong-Fong; Pfeifer, Gerd P

    2008-12-15

    Epigenetic changes are strongly associated with cancer development. DNA hypermethylation is associated with gene silencing and is often observed in CpG islands. Recently, it was suggested that aberrant CpG island methylation in tumors is directed by Polycomb (PcG) proteins. However, specific mechanisms responsible for methylation of PcG target genes in cancer are not known. Chronic infection and inflammation contribute to up to 25% of all cancers worldwide. Using glutathione peroxidase, Gpx1 and Gpx2, double knockout (Gpx1/2-KO) mice as a model of inflammatory bowel disease predisposing to intestinal cancer, we analyzed genome-wide DNA methylation in the mouse ileum during chronic inflammation, aging, and cancer. We found that inflammation leads to aberrant DNA methylation in PcG target genes, with 70% of the approximately 250 genes methylated in the inflamed tissue being PcG targets in embryonic stem cells and 59% of the methylated genes being marked by H3K27 trimethylation in the ileum of adult wild-type mice. Acquisition of DNA methylation at CpG islands in the ileum of Gpx1/2-KO mice frequently correlates with loss of H3K27 trimethylation at the same loci. Inflammation-associated DNA methylation occurs preferentially in tissue-specific silent genes and, importantly, is much more frequently represented in tumors than is age-dependent DNA methylation. Sixty percent of aberrant methylation found in tumors is also present in the inflamed tissue. In summary, inflammation creates a signature of aberrant DNA methylation, which is observed later in the malignant tissue and is directed by the PcG complex.

  10. Intestinal microbiota sustains inflammation and autoimmunity induced by hypomorphic RAG defects

    Science.gov (United States)

    Rigoni, Rosita; Fontana, Elena; Guglielmetti, Simone; Fosso, Bruno; D’Erchia, Anna Maria; Maina, Virginia; Taverniti, Valentina; Castiello, Maria Carmina; Mantero, Stefano; Pacchiana, Giovanni; Musio, Silvia; Pedotti, Rosetta; Selmi, Carlo; Mora, J. Rodrigo; Pesole, Graziano; Vezzoni, Paolo; Poliani, Pietro Luigi; Grassi, Fabio

    2016-01-01

    Omenn syndrome (OS) is caused by hypomorphic Rag mutations and characterized by a profound immunodeficiency associated with autoimmune-like manifestations. Both in humans and mice, OS is mediated by oligoclonal activated T and B cells. The role of microbial signals in disease pathogenesis is debated. Here, we show that Rag2R229Q knock-in mice developed an inflammatory bowel disease affecting both the small bowel and colon. Lymphocytes were sufficient for disease induction, as intestinal CD4 T cells with a Th1/Th17 phenotype reproduced the pathological picture when transplanted into immunocompromised hosts. Moreover, oral tolerance was impaired in Rag2R229Q mice, and transfer of wild-type (WT) regulatory T cells ameliorated bowel inflammation. Mucosal immunoglobulin A (IgA) deficiency in the gut resulted in enhanced absorption of microbial products and altered composition of commensal communities. The Rag2R229Q microbiota further contributed to the immunopathology because its transplant into WT recipients promoted Th1/Th17 immune response. Consistently, long-term dosing of broad-spectrum antibiotics (ABXs) in Rag2R229Q mice ameliorated intestinal and systemic autoimmunity by diminishing the frequency of mucosal and circulating gut-tropic CCR9+ Th1 and Th17 T cells. Remarkably, serum hyper-IgE, a hallmark of the disease, was also normalized by ABX treatment. These results indicate that intestinal microbes may play a critical role in the distinctive immune dysregulation of OS. PMID:26926994

  11. Intestinal inflammation influences α-MSH reactive autoantibodies: relevance to food intake and body weight.

    Science.gov (United States)

    Coquerel, Quentin; Sinno, Maria Hamze; Boukhettala, Nabile; Coëffier, Moïse; Terashi, Mutsumi; Bole-Feysot, Christine; Breuillé, Denis; Déchelotte, Pierre; Fetissov, Sergueï O

    2012-01-01

    Autoantibodies reacting with alpha-melanocyte-stimulating hormone (α-MSH), an anorexigenic neuropeptide, are involved in regulation of feeding. In this work we studied if intestinal inflammation (mucositis) may influence α-MSH autoantibodies production relevant to food intake and body weight. Mucositis and anorexia were produced in Sprague-Dawley rats by methotrexate (MTX, 2.5mg/kg/day, for three days, subcutaneously). Plasma levels of total IgG and of α-MSH autoantibodies were measured during and after MTX-induced mucositis and were compared with pair-fed and ad libitum-fed controls. Effects of intraperitoneal injections of rabbit anti-α-MSH IgG (3 or 10 μg/day/rat) on MTX-induced anorexia and on plasma α-MSH peptide concentration were separately studied. Here we show that in MTX rats, intestinal mucositis and anorexia were accompanied by decreased plasma levels of both total IgG and of α-MSH autoantibodies while refeeding was characterized by their elevated levels. In spite of similar food intake in MTX and pair-fed rats, recovery of body weight was delayed by at least 1 week in the MTX group. During refeeding and body weight deficit in MTX rats, α-MSH IgG autoantibody levels correlated negatively with food to water intake ratios. Injections of anti-α-MSH IgG induced a dose-dependent attenuation of food intake and body weight regain in MTX-treated rats accompanied by increased concentrations of α-MSH peptide which correlated positively with plasma levels of α-MSH autoantibodies. These data show that intestinal inflammation, independently from food restriction, affects general humoral immune response which may influence food intake and body weight control via modulation of α-MSH plasma concentration by α-MSH reactive autoantibodies. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Transcriptional modulation of intestinal innate defense/inflammation genes by preterm infant microbiota in a humanized gnotobiotic mouse model.

    Science.gov (United States)

    Lu, Lei; Yu, Yueyue; Guo, Yuee; Wang, Yunwei; Chang, Eugene B; Claud, Erika C

    2015-01-01

    It is known that postnatal functional maturation of the small intestine is facilitated by microbial colonization of the gut. Preterm infants exhibit defects in gut maturation, weak innate immunity against intestinal infection and increased susceptibility to inflammatory disorders, all of which may be related to the inappropriate microbial colonization of their immature intestines. The earliest microbes to colonize the preterm infant gut encounter a naïve, immature intestine. Thus this earliest microbiota potentially has the greatest opportunity to fundamentally influence intestinal development and immune function. The aim of this study was to characterize the effect of early microbial colonization on global gene expression in the distal small intestine during postnatal gut development. Gnotobiotic mouse models with experimental colonization by early (prior to two weeks of life) intestinal microbiota from preterm human infants were utilized. Microarray analysis was used to assess global gene expression in the intestinal epithelium. Multiple intestinal genes involved in metabolism, cell cycle regulation, cell-cell or cell-extracellular matrix communication, and immune function are developmental- and intestinal microbiota- regulated. Using a humanized gnotobiotic mouse model, we demonstrate that certain early preterm infant microbiota from prior to 2 weeks of life specifically induce increased NF-κB activation and a phenotype of increased inflammation whereas other preterm microbiota specifically induce decreased NF-κB activation. These fundamental differences correlate with altered clinical outcomes and suggest the existence of optimal early microbial communities to improve health outcomes.

  13. Myeloid-derived miR-223 regulates intestinal inflammation via repression of the NLRP3 inflammasome

    Science.gov (United States)

    Khailova, Ludmila; Tye, Hazel; Jedlicka, Paul; Gerich, Mark E.; Mack, Matthias; Robertson, Avril A.B.; Dinarello, Charles A.; O’Neill, Luke A.; Eltzschig, Holger K.

    2017-01-01

    MicroRNA (miRNA)-mediated RNA interference regulates many immune processes, but how miRNA circuits orchestrate aberrant intestinal inflammation during inflammatory bowel disease (IBD) is poorly defined. Here, we report that miR-223 limits intestinal inflammation by constraining the nlrp3 inflammasome. miR-223 was increased in intestinal biopsies from patients with active IBD and in preclinical models of intestinal inflammation. miR-223-/y mice presented with exacerbated myeloid-driven experimental colitis with heightened clinical, histopathological, and cytokine readouts. Mechanistically, enhanced NLRP3 inflammasome expression with elevated IL-1β was a predominant feature during the initiation of colitis with miR-223 deficiency. Depletion of CCR2+ inflammatory monocytes and pharmacologic blockade of IL-1β or NLRP3 abrogated this phenotype. Generation of a novel mouse line, with deletion of the miR-223 binding site in the NLRP3 3′ untranslated region, phenocopied the characteristics of miR-223-/y mice. Finally, nanoparticle-mediated overexpression of miR-223 attenuated experimental colitis, NLRP3 levels, and IL-1β release. Collectively, our data reveal a previously unappreciated role for miR-223 in regulating the innate immune response during intestinal inflammation. PMID:28487310

  14. Plasma endocannabinoid levels in lean, overweight and obese humans: relationships with intestinal permeability markers, inflammation and incretin secretion.

    Science.gov (United States)

    Little, Tanya J; Cvijanovic, Nada; DiPatrizio, Nicholas V; Argueta, Donovan A; Rayner, Christopher K; Feinle-Bisset, Christine; Young, Richard L

    2018-02-13

    Intestinal production of endocannabinoid and oleoylethanolamide (OEA) is impaired in high-fat diet/obese rodents, leading to reduced satiety. Such diets also alter the intestinal microbiome in association with enhanced intestinal permeability and inflammation, however little is known of these effects in humans. This study aimed to: (i) evaluate effects of lipid on plasma anandamide (AEA), 2-arachidonyl-sn-glycerol (2-AG) and OEA in humans, and (ii) examine relationships with intestinal permeability, inflammation markers and incretin hormone secretion. 20 lean, 18 overweight and 19 obese participants underwent intraduodenal Intralipid® infusion (2 kcal/min) with collection of endoscopic duodenal biopsies and blood. Plasma AEA, 2-AG, and OEA (HPLC/tandem mass spectrometry), tumour necrosis factor-α (TNF-α), glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) (multiplex), and duodenal expression of occludin, zona-occludin-1 (ZO-1), intestinal-alkaline-phosphatase (IAP), and toll-like receptor-4 (TLR4) (RT-PCR), were assessed. Fasting plasma AEA was increased in obese, compared with lean and overweight (Plean (Plean and overweight. The relationships between plasma AEA with duodenal ZO-1 and IAP, and GIP, suggest that altered endocannabinoid signalling may contribute to changes in intestinal permeability, inflammation and incretin release in human obesity.

  15. Specific microbiome changes in a mouse model of parenteral nutrition associated liver injury and intestinal inflammation.

    Science.gov (United States)

    Harris, J Kirk; El Kasmi, Karim C; Anderson, Aimee L; Devereaux, Michael W; Fillon, Sophie A; Robertson, Charles E; Wagner, Brandie D; Stevens, Mark J; Pace, Norman R; Sokol, Ronald J

    2014-01-01

    Parenteral nutrition (PN) has been a life-saving treatment in infants intolerant of enteral feedings. However, PN is associated with liver injury (PN Associated Liver Injury: PNALI) in a significant number of PN-dependent infants. We have previously reported a novel PNALI mouse model in which PN infusion combined with intestinal injury results in liver injury. In this model, lipopolysaccharide activation of toll-like receptor 4 signaling, soy oil-derived plant sterols, and pro-inflammatory activation of Kupffer cells (KCs) played key roles. The objective of this study was to explore changes in the intestinal microbiome associated with PNALI. Microbiome analysis in the PNALI mouse identified specific alterations within colonic microbiota associated with PNALI and further association of these communities with the lipid composition of the PN solution. Intestinal inflammation or soy oil-based PN infusion alone (in the absence of enteral feeds) caused shifts within the gut microbiota. However, the combination resulted in accumulation of a specific taxon, Erysipelotrichaceae (23.8% vs. 1.7% in saline infused controls), in PNALI mice. Moreover, PNALI was markedly attenuated by enteral antibiotic treatment, which also was associated with significant reduction of Erysipelotrichaceae (0.6%) and a Gram-negative constituent, the S24-7 lineage of Bacteroidetes (53.5% in PNALI vs. 0.8%). Importantly, removal of soy oil based-lipid emulsion from the PN solution resulted in significant reduction of Erysipelotrichaceae as well as attenuation of PNALI. Finally, addition of soy-derived plant sterol (stigmasterol) to fish oil-based PN restored Erysipelotrichaceae abundance and PNALI. Soy oil-derived plant sterols and the associated specific bacterial groups in the colonic microbiota are associated with PNALI. Products from these bacteria may directly trigger activation of KCs and promote PNALI. Furthermore, the results indicate that lipid modification of PN solutions may alter

  16. Maternal Obesity Induces Sustained Inflammation in Both Fetal and Offspring Large Intestine of Sheep

    Science.gov (United States)

    Yan, Xu; Huang, Yan; Wang, Hui; Du, Min; Hess, Bret W.; Ford, Stephen P.; Nathanielsz, Peter W.; Zhu, Mei-Jun

    2010-01-01

    Background Both maternal obesity and inflammatory bowel diseases (IBDs) are increasing. It was hypothesized that maternal obesity induces an inflammatory response in the fetal large intestine, predisposing offspring to IBDs. Methods Nonpregnant ewes were assigned to a control (Con, 100% of National Research Council [NRC] recommendations) or obesogenic (OB, 150% of NRC) diet from 60 days before conception. The large intestine was sampled from fetuses at 135 days (term 150 days) after conception and from offspring lambs at 22.5 ± 0.5 months of age. Results Maternal obesity enhanced mRNA expression tumor necrosis factor (TNF)α, interleukin (IL)1α, IL1β, IL6, IL8, and monocyte/macrophage chemotactic protein-1 (MCP1), as well as macrophage markers, CD11b, CD14, and CD68 in fetal gut. mRNA expression of Toll-like receptor (TLR) 2 and TLR4 was increased in OB versus Con fetuses; correspondingly, inflammatory NF-κB and JNK signaling pathways were also upregulated. Both mRNA expression and protein content of transforming growth factor (TGF) β was increased. The IL-17A mRNA expression and protein content was higher in OB compared to Con samples, which was associated with fibrosis in the large intestine of OB fetuses. Similar inflammatory responses and enhanced fibrosis were detected in OB compared to Con offspring. Conclusions Maternal obesity induced inflammation and enhanced expression of proinflammatory cytokines in fetal and offspring large intestine, which correlated with increased TGFβ and IL17 expression. These data show that maternal obesity may predispose offspring gut to IBDs. PMID:21674707

  17. Oral administration of Bifidobacterium bifidum G9-1 alleviates rotavirus gastroenteritis through regulation of intestinal homeostasis by inducing mucosal protective factors.

    Directory of Open Access Journals (Sweden)

    Tomohiro Kawahara

    Full Text Available Human rotavirus (RV infection is a leading cause of dehydrating diarrhea in infants and young children worldwide. Since therapeutic approaches to RV gastroenteritis are limited to alleviation of dehydration with oral rehydration solutions, more direct approaches to palliate symptoms of RV gastroenteritis are required. Treatments with probiotics have been increasingly recognized as alternative safe and low cost treatments for moderate infectious diarrhea. In this study, Bifidobacterium bifidum G9-1 (BBG9-1, which has been used as an intestinal drug for several decades, was shown to have a remarkable protective effect against RV gastroenteritis in a suckling mice model. As well as prophylactic oral administration of BBG9-1 from 2 days before RV infection, therapeutic oral administration of BBG9-1 from 1 day after RV infection significantly alleviated RV-induced diarrhea. Therapeutic administration of BBG9-1 reduced various types of damage in the small intestine, such as epithelial vacuolization and villous shortening, and significantly diminished the infectious RV titer in mixtures of cecal contents and feces. It was also shown that therapeutic administration of BBG9-1 significantly increased the number of acidic mucin-positive goblet cells and the gene expression of mucosal protective factors including MUC2, MUC3, MUC4, TGFβ1 and TFF3 in the small intestine. This led to alleviation of low gut permeability shown as decreased gene expression levels of occludin, claudin-1 and villin-1 after RV infection. Furthermore, in the small intestine, therapeutic administration of BBG9-1 significantly palliated the decreased gene expression of SGLT-1, which plays an important role in water absorption. In the large intestine, administered BBG9-1 was shown to replicate to assimilate undigested nutrients, resulting in normalization of the abnormally high osmotic pressure. These results suggested that water malabsorption caused by RV infection was alleviated in

  18. Oral administration of Bifidobacterium bifidum G9-1 alleviates rotavirus gastroenteritis through regulation of intestinal homeostasis by inducing mucosal protective factors.

    Science.gov (United States)

    Kawahara, Tomohiro; Makizaki, Yutaka; Oikawa, Yosuke; Tanaka, Yoshiki; Maeda, Ayako; Shimakawa, Masaki; Komoto, Satoshi; Moriguchi, Kyoko; Ohno, Hiroshi; Taniguchi, Koki

    2017-01-01

    Human rotavirus (RV) infection is a leading cause of dehydrating diarrhea in infants and young children worldwide. Since therapeutic approaches to RV gastroenteritis are limited to alleviation of dehydration with oral rehydration solutions, more direct approaches to palliate symptoms of RV gastroenteritis are required. Treatments with probiotics have been increasingly recognized as alternative safe and low cost treatments for moderate infectious diarrhea. In this study, Bifidobacterium bifidum G9-1 (BBG9-1), which has been used as an intestinal drug for several decades, was shown to have a remarkable protective effect against RV gastroenteritis in a suckling mice model. As well as prophylactic oral administration of BBG9-1 from 2 days before RV infection, therapeutic oral administration of BBG9-1 from 1 day after RV infection significantly alleviated RV-induced diarrhea. Therapeutic administration of BBG9-1 reduced various types of damage in the small intestine, such as epithelial vacuolization and villous shortening, and significantly diminished the infectious RV titer in mixtures of cecal contents and feces. It was also shown that therapeutic administration of BBG9-1 significantly increased the number of acidic mucin-positive goblet cells and the gene expression of mucosal protective factors including MUC2, MUC3, MUC4, TGFβ1 and TFF3 in the small intestine. This led to alleviation of low gut permeability shown as decreased gene expression levels of occludin, claudin-1 and villin-1 after RV infection. Furthermore, in the small intestine, therapeutic administration of BBG9-1 significantly palliated the decreased gene expression of SGLT-1, which plays an important role in water absorption. In the large intestine, administered BBG9-1 was shown to replicate to assimilate undigested nutrients, resulting in normalization of the abnormally high osmotic pressure. These results suggested that water malabsorption caused by RV infection was alleviated in mice administered

  19. A role for interleukin-33 in T(H)2-polarized intestinal inflammation?

    DEFF Research Database (Denmark)

    Seidelin, J B; Rogler, G; Nielsen, O H

    2011-01-01

    Interleukin 33 (IL-33) is a recently discovered cytokine member of the IL-1 superfamily that is widely expressed in fixed tissue cells, including endothelial and epithelial cells. IL-33 induces helper T cells, mast cells, eosinophils, and basophils to produce type-2 cytokines through binding...... to the ST2/IL-1 receptor accessory protein complex. Recent studies have shown IL-33 to be upregulated in intestinal parasite infection and in epithelial cells and myofibroblasts in ulcerative colitis (UC). The findings point to a role for IL-33 in directing the T(H)2-type immune responses in these types...... of mucosal inflammation. As the IL-33/ST2 receptor axis can be manipulated by various blocking antibodies, this could be a potential therapeutic target in the future treatment of UC....

  20. Electroacupuncture Inhibits Inflammation Reaction by Upregulating Vasoactive Intestinal Peptide in Rats with Adjuvant-Induced Arthritis

    Directory of Open Access Journals (Sweden)

    Tian-Feng He

    2011-01-01

    Full Text Available Acupuncture is emerging as an alternative therapy for rheumatoid arthritis (RA. However, the molecular mechanism underlying this beneficial effect of acupuncture has not been fully understood. Here, we demonstrated that electroacupuncture at acupoints Zusanli (ST36, Xuanzhong (GB39; and Shenshu (BL23 markedly decreased the paw swelling and the histologic scores of inflammation in the synovial tissue, and reduced the body weight loss in an adjuvant-induced arthritis rat model. However, the electrical stimulation at nonacupoint did not produce any beneficial effects against the experimental arthritis. Most interestingly, the electroacupuncture treatment resulted in an enhanced immunostaining for vasoactive intestinal peptide (VIP, a potent anti-inflammatory neuropeptide, in the synovial tissue. Moreover, the VIP-immunostaining intensity was significantly negatively correlated with the scores of inflammation in the synovial tissue (r=−0.483, P=.0026. In conclusion, these findings suggest that electroacupuncture may offer therapeutic benefits for the treatment of RA, at least partially through the induction of VIP expression.

  1. CD4+CD25+ regulatory T cells have divergent effects on intestinal inflammation in IL-10 gene-deficient mice.

    Science.gov (United States)

    Sydora, Beate C; MacFarlane, Sarah M; Tavernini, Michele M; Doyle, Jason S G; Fedorak, Richard N

    2008-06-01

    The regulatory effect of murine CD4+CD25+ T-cells in vivo appears to be dependent on the secretion of IL-10. The lack of IL-10 in the IL-10 gene-deficient mouse has a profoundly negative effect on the mouse's regulation of the response to intestinal bacteria, resulting in severe enterocolitis. We investigated the effect of neonatal injection with wild-type CD4+CD25+ T-cells on the intestinal immune response in IL-10 gene-deficient mice. At the time of analysis, 8-15 weeks later, all mice demonstrated an increased, antigen-stimulated systemic response. However, the intestinal response was divergent with about half of the mice developing an intestinal inflammation with a high injury score, the other half demonstrating a remarkable reduction in injury score with a marked decrease in intestinal IFNgamma release. Our data demonstrate that CD4+CD25+ T-cells can be activated in IL-10 gene-deficient mice and that this stimulation under stringent conditions has the potential to reduce intestinal inflammation.

  2. Effects of flavonoids on intestinal inflammation, barrier integrity and changes in gut microbiota during diet-induced obesity.

    Science.gov (United States)

    Gil-Cardoso, Katherine; Ginés, Iris; Pinent, Montserrat; Ardévol, Anna; Blay, Mayte; Terra, Ximena

    2016-12-01

    Diet-induced obesity is associated with low-grade inflammation, which, in most cases, leads to the development of metabolic disorders, primarily insulin resistance and type 2 diabetes. Although prior studies have implicated the adipose tissue as being primarily responsible for obesity-associated inflammation, the latest discoveries have correlated impairments in intestinal immune homeostasis and the mucosal barrier with increased activation of the inflammatory pathways and the development of insulin resistance. Therefore, it is essential to define the mechanisms underlying the obesity-associated gut alterations to develop therapies to prevent and treat obesity and its associated diseases. Flavonoids appear to be promising candidates among the natural preventive treatments that have been identified to date. They have been shown to protect against several diseases, including CVD and various cancers. Furthermore, they have clear anti-inflammatory properties, which have primarily been evaluated in non-intestinal models. At present, a growing body of evidence suggests that flavonoids could exert a protective role against obesity-associated pathologies by modulating inflammatory-related cellular events in the intestine and/or the composition of the microbiota populations. The present paper will review the literature to date that has described the protective effects of flavonoids on intestinal inflammation, barrier integrity and gut microbiota in studies conducted using in vivo and in vitro models.

  3. Pioglitazone alleviates inflammation in diabetic mice fed a high-fat diet via inhibiting advanced glycation end-product-induced classical macrophage activation.

    Science.gov (United States)

    Jin, Xian; Liu, Liang; Zhou, Zhong'e; Ge, Junhua; Yao, Tongqing; Shen, Chengxing

    2016-06-01

    Classically activated macrophages (M1) are associated with inflammation in diabetic patients. Inflammation is a known risk factor in diabetes. The present study tested the hypothesis that pioglitazone (PIO) alleviates inflammation in diabetic mice fed a high-fat diet by inhibiting advanced glycation end-product (AGE)-induced classical macrophage activation. It was found that AGE treatment promoted the transcription of pro-inflammatory molecules and M1 surface markers, whereas PIO increased the expression of anti-inflammatory genes and decreased the expression of pro-inflammatory mediators in bone marrow-derived macrophages (BMDMs) in a dose-dependent manner. Furthermore, pretreatment with PIO abrogated the effects of AGE on pro-inflammatory markers and partly inhibited AGE-induced nuclear factor-κB (NF-κB) activation. PIO treatment partly reduced the inflammatory phenotype in diabetic ApoE(-/-) mice, and significantly reduced NF-κB activation in plaques. Therefore, we conclude that PIO blocks classical activation of macrophages and attenuates inflammation in mouse models of diabetes. © 2016 Federation of European Biochemical Societies.

  4. The tumor necrosis factor family member TNFSF14 (LIGHT) is required for resolution of intestinal inflammation in mice.

    Science.gov (United States)

    Krause, Petra; Zahner, Sonja P; Kim, Gisen; Shaikh, Raziyah B; Steinberg, Marcos W; Kronenberg, Mitchell

    2014-06-01

    The pathogenesis of inflammatory bowel disease (IBD) is associated with a dysregulated mucosal immune response. Expression of the tumor necrosis factor (TNF) superfamily member 14 (TNFSF14, also known as LIGHT [homologous to lymphotoxins, exhibits inducible expression, and competes with HSV glycoprotein D for HVEM, a receptor expressed by T lymphocytes]) on T cells is involved in their activation; transgenic expression of LIGHT on T cells in mice promotes inflammation in multiple organs, including intestine. We investigated the roles for LIGHT in recovery from intestinal inflammation in mice. We studied the role of LIGHT in intestinal inflammation using Tnfsf14(-/-) and wild-type mice. Colitis was induced by transfer of CD4(+)CD45RB(high) T cells into Rag1(-/-) or Tnfsf14(-/-)Rag1(-/-) mice, or by administration of dextran sulfate sodium to Tnfsf14(-/-) or wild-type C57BL/6J mice. Mice were weighed, colon tissues were collected and measured, and histology analyses were performed. We measured infiltrating cell populations and expression of cytokines, chemokines, and LIGHT. After administration of dextran sulfate sodium, Tnfsf14(-/-) mice developed more severe colitis than controls, based on their reduced survival, accelerated loss of body weight, and histologic scores. LIGHT protected mice from colitis via the lymphotoxin β receptor and was expressed mainly by myeloid cells in the colon. Colons of Tnfsf14(-/-) mice also had increased accumulation of innate immune cells and higher levels of cytokines than colons from control mice. LIGHT, therefore, appears to regulate inflammation in the colon. Tnfsf14(-/-) mice develop more severe colitis than control mice. LIGHT signals through the lymphotoxin β receptor in the colon to regulate the innate immune response and mediate recovery from intestinal inflammation. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

  5. Transient inhibition of ROR-γt therapeutically limits intestinal inflammation by reducing TH17 cells and preserving ILC3

    Science.gov (United States)

    Withers, David R.; Hepworth, Matthew R.; Wang, Xinxin; Mackley, Emma C.; Halford, Emily E.; Dutton, Emma E.; Marriott, Clare L.; Brucklacher-Waldert, Verena; Veldhoen, Marc; Kelsen, Judith; Baldassano, Robert N.; Sonnenberg, Gregory F.

    2016-01-01

    RAR-related orphan receptor γt (ROR-γt) directs differentiation of pro-inflammatory T helper 17 (TH17) cells and is a potential therapeutic target in chronic autoimmune and inflammatory diseases1–3. However, ROR-γt-dependent group 3 innate lymphoid cells (ILC3s) provide essential immunity and tissue protection in the intestine4–11, suggesting that targeting ROR-γt could also result in impaired host defense to infection or enhanced tissue damage. Here, we demonstrate that transient chemical inhibition of ROR-γt in mice selectively reduces cytokine production from TH17 cells but not ILC3s in the context of intestinal infection with Citrobacter rodentium, resulting in preserved innate immunity. Transient genetic deletion of ROR-γt in mature ILC3s also did not impair cytokine responses in the steady state or during infection. Finally, pharmacologic inhibition of ROR-γt provided therapeutic benefit in mouse models of intestinal inflammation, and reduced the frequencies of TH17 cells but not ILC3s isolated from primary intestinal samples of individuals with inflammatory bowel disease (IBD). Collectively, these results reveal differential requirements for ROR-γt in the maintenance of TH17 cell versus ILC3 responses, and suggest that transient inhibition of ROR-γt is a safe and effective therapeutic approach during intestinal inflammation. PMID:26878233

  6. The macrophage system in the intestinal muscularis externa during inflammation: an immunohistochemical and quantitative study of osteopetrotic mice

    DEFF Research Database (Denmark)

    Mikkelsen, Hanne Birte; Larsen, Jytte Overgaard; Hadberg, Hanne

    2008-01-01

    Intestinal inflammation results in disturbed intestinal motility in humans as well as in animal models. This altered function of smooth muscle cells and/or the enteric nervous system may be caused by activation of macrophages in muscularis externa and a thereby following release of cytokines...... and chemokines that causes influx of mononuclear cells and neutrophilic granulocytes. We subjected osteopetrotic (op/op) mice that lack certain macrophage subtypes, e.g. macrophages in the muscularis externa and +/+ mice to LPS to induce inflammatory cell influx. The densities of F4/80(+), MHCII...

  7. Characterization and pharmacological modulation of intestinal inflammation induced by ionizing radiation; Caracterisation et modulation pharmacologique de l'inflammation intestinale induite par les rayonnements ionisants

    Energy Technology Data Exchange (ETDEWEB)

    Gremy, O

    2006-12-15

    The use of radiation therapy to treat abdominal and pelvic malignancies inevitably involves exposure of healthy intestinal tissues which are very radiosensitive. As a result, most patients experience symptoms such as abdominal pain, nausea and diarrhea. Such symptoms are associated with acute damage to intestine mucosa including radio-induced inflammatory processes. With a rat model of colorectal fractionated radiation, we have shown a gradual development of a colonic inflammation during radiation planning, without evident tissue injury. This radio-induced inflammation is characterized not only by the sur expressions of pro-inflammatory cytokines and chemokines, a NF-kB activation, but also by a repression of anti-inflammatory cytokines and the nuclear receptors PPARa and RXRa, both involved in inflammation control. This early inflammation is associated with a discreet neutrophil recruitment and a macrophage accumulation. Macrophages are still abnormally numerous in tissue 27 weeks after the last day of irradiation. Inflammatory process is the most often related to a specific immune profile, either a type Th1 leading to a cellular immune response, or a type Th2 for humoral immunity. According to our studies, a unique abdominal radiation in the rat induces an ileum inflammation and an immune imbalance resulting in a Th2-type profile. Inhibiting this profile is important as its persistence promotes chronic inflammation, predisposition to bacterial infections and fibrosis which is the main delayed side-effect of radiotherapy. The treatment of rats with an immuno-modulator compound, the caffeic acid phenethyl ester (C.A.P.E.), have the potential to both reduce ileal mucosal inflammation and inhibit the radio-induced Th2 status. In order to search new therapeutic molecular target, we has been interested in the PPARg nuclear receptor involved in the maintenance of colon mucosal integrity. In our abdominal irradiation model, we have demonstrated that the prophylactic

  8. Secretoglobin Superfamily Protein SCGB3A2 Alleviates House Dust Mite-Induced Allergic Airway Inflammation in Mice.

    Science.gov (United States)

    Yoneda, Mitsuhiro; Xu, Lei; Kajiyama, Hiroaki; Kawabe, Shuko; Paiz, Jorge; Ward, Jerrold M; Kimura, Shioko

    2016-01-01

    Secretoglobin (SCGB) 3A2, a novel, lung-enriched, cytokine-like, secreted protein of small molecular weight, was demonstrated to exhibit various biological functions including anti-inflammatory, antifibrotic and growth-factor activities. Anti-inflammatory activity was uncovered using the ovalbumin-induced allergic airway inflammation model. However, further validation of this activity using knockout mice in a different allergic inflammation model is necessary in order to establish the antiallergic inflammatory role for this protein. Scgb3a2-null (Scgb3a2-/-) mice were subjected to nasal inhalation of Dermatophagoides pteronyssinus extract for 5 days/week for 5 consecutive weeks; control mice received nasal inhalation of saline as a comparator. Airway inflammation was assessed by histological analysis, the number of inflammatory cells and various Th2-type cytokine levels in the lungs and bronchoalveolar lavage fluids by qRT-PCR and ELISA, respectively. Exacerbated inflammation was found in the airway of Scgb3a2-/- mice subjected to house dust mite (HDM)-induced allergic airway inflammation compared with saline-treated control groups. All the inflammation end points were increased in the Scgb3a2-/- mice. The Ccr4 and Ccl17 mRNA levels were higher in HDM-treated lungs of Scgb3a2-/- mice than wild-type mice or saline-treated Scgb3a2-/- mice, whereas no changes were observed for Ccr3 and Ccl11 mRNA levels. These results demonstrate that SCGB3A2 has an anti-inflammatory activity in the HDM-induced allergic airway inflammation model, in which SCGB3A2 may modulate the CCR4-CCL17 pathway. SCGB3A2 may provide a useful tool to treat allergic airway inflammation, and further studies on the levels and function of SCGB3A2 in asthmatic patients are warranted. © 2016 S. Karger AG, Basel.

  9. Impact of matrine on inflammation related factors in rat intestinal microvascular endothelial cells.

    Science.gov (United States)

    Suo, Zhanwei; Liu, Ye; Ferreri, Miro; Zhang, Tao; Liu, Zhongjie; Mu, Xiang; Han, Bo

    2009-09-25

    Matrine (MT) is a main active ingredient of Sophora flavescens roots, which is used in Traditional Chinese Medicine (TCM) for the treatment of inflammations like enteritis, hepatitis and atopic dermatitis. Aim of the study is to gain insight into the effects of MT on nitric oxide (NO) release, intracellular NO production, and endothelial nitric oxide synthase (eNOS) level in second generation rat intestinal microvascular endothelial cells (RIMECs). Moreover, the effects of MT on soluble intercellular adhesion molecule-1 (sICAM-1), interleukin-6 (IL-6) and interleukin-8 (IL-8) production induced by lipopolysaccharide (LPS) in these cells were evaluated. Isolated and identified RIMECs cultures were exposed to different concentrations of matrine, and changes in extra- and intracellular NO concentrations were measured in dependance of time by Griess reaction or DAF-FM diacetate. Obtained cell cultures were solitude treated with lypopolysaccharide (LPS) or combined with MT to observe impacts on sICAM-1, IL-6 and IL-8 concentration in culture supernatants by ELISA. Matrine dose-dependently increased the concentration of NO in culture supernatant of RIMECs. Exposure of MT resulted in a steady intracellular NO increase pattern under different concentrations with different values and has an increasing effect on eNOS concentration at a long time exposure. Additionally, matrine reduced the increasing effect of LPS on the production of IL-6, IL-8, and sICAM-1 in RIMECs. These results show that matrine may serve as a protective agent against tissue damage in inflammation by improving NO-dependent vasomotion and inhibiting inflammatory cytokines induced by LPS.

  10. Enhanced platelet adhesion induces angiogenesis in intestinal inflammation and inflammatory bowel disease microvasculature

    Science.gov (United States)

    Rutella, Sergio; Vetrano, Stefania; Correale, Carmen; Graziani, Cristina; Sturm, Andreas; Spinelli, Antonino; De Cristofaro, Raimondo; Repici, Alessandro; Malesci, Alberto; Danese, Silvio

    2011-01-01

    Abstract Although angiogenesis is viewed as a fundamental component of inflammatory bowel disease (IBD) pathogenesis, we presently lack a thorough knowledge of the cell type(s) involved in its induction and maintenance in the inflamed intestinal mucosa. This study aimed to determine whether platelet (PLT) adhesion to inflamed intestinal endothelial cells of human origin may favour angiogenesis. Unstimulated or thrombin-activated human PLT were overlaid on resting or tumour necrosis factor (TNF)-α-treated human intestinal microvascular endothelial cells (HIMEC), in the presence or absence of blocking antibodies to either vascular cell adhesion molecule (VCAM)-1, intercellular adhesion molecule (ICAM)-1, integrin αvβ3, tissue factor (TF) or fractalkine (FKN). PLT adhesion to HIMEC was evaluated by fluorescence microscopy, and release of angiogenic factors (VEGF and soluble CD40L) was measured by ELISA. A matrigel tubule formation assay was used to estimate PLT capacity to induce angiogenesis after co-culturing with HIMEC. TNF-α up-regulated ICAM-1, αvβ3 and FKN expression on HIMEC. When thrombin-activated PLT were co-cultured with unstimulated HIMEC, PLT adhesion increased significantly, and this response was further enhanced by HIMEC activation with TNF-α. PLT adhesion to HIMEC was VCAM-1 and TF independent but ICAM-1, FKN and integrin αvβ3 dependent. VEGF and sCD40L were undetectable in HIMEC cultures either before or after TNF-α stimulation. By contrast, VEGF and sCD40L release significantly increased when resting or activated PLT were co-cultured with TNF-α-pre-treated HIMEC. These effects were much more pronounced when PLT were derived from IBD patients. Importantly, thrombin-activated PLT promoted tubule formation in HIMEC, a functional estimate of their angiogenic potential. In conclusion, PLT adhesion to TNF-α-pre-treated HIMEC is mediated by ICAM-1, FKN and αvβ3, and is associated with VEGF and sCD40L release. These findings suggest that

  11. Anti-inflammatory, anticholinesterase and antioxidant activity of leaf extracts of twelve plants used traditionally to alleviate pain and inflammation in South Africa.

    Science.gov (United States)

    Dzoyem, J P; Eloff, J N

    2015-02-03

    Oxidative stress and inflammatory conditions are among the pathological features associated with the central nervous system in Alzheimer׳s disease. Traditionally, medicinal plants have been used to alleviate inflammation, pains and also other symptoms possibly associated with Alzheimer׳s disease. Therefore, the present study was designed to determine the in vitro anti-inflammatory, antioxidant and anticholinesterase activity of twelve South African medicinal plants traditionally used to alleviate pain and inflammation. Nitric oxide (NO) production in LPS-activated RAW 264.7 macrophages and 15-lipoxygenase (LOX) inhibitory assay were used to evaluate the anti-inflammatory activity. Acetylcholinesterase inhibition was assessed by using a modification of the Ellman׳s method. Antioxidant activity, total phenolic and total flavonoids contents were determined using standard in vitro methods. The extract of Burkea africana had the highest anti-15-lipoxygenase activity with 85.92% inhibition at 100µg/mL. All the extracts tested inhibited nitric oxide (NO) production in a dose dependant manner in LPS-stimulated RAW 264.7 macrophages. However, extracts from Leucaena leucocephala, Lippia javanica inhibited the production of NO by 97% at a concentration of 25µg/mL. In addition, both Leucaena leucocephala and Englerophytum magaliesmontanum had strong activity against acetylcholinesterase with IC50 values of 118µg/mL and 160µg/mL respectively. Hight levels of phenolics and flavonoids were found in Leucaena leucocephala, Lippia javanica and Burkea africana. The correlation with antioxidant activities was not strong indicating that other metabolites may also be involved in antioxidant activity. The results obtained in this study validate the use of leaf extracts of these plants in South African traditional medicine against inflammation. Extracts of these plants species might be of value in the management of various diseases emerging from oxidative stress and related

  12. An orally active Cannabis extract with high content in cannabidiol attenuates chemical induced intestinal inflammation and hypermotility in the mouse

    Directory of Open Access Journals (Sweden)

    Ester Pagano

    2016-10-01

    Full Text Available Anecdotal and scientific evidence suggests that Cannabis use may be beneficial in inflammatory bowel disease (IBD patients. Here, we have investigated the effect of a standardized Cannabis sativa extract with high content of cannabidiol (CBD, here named CBD BDS for CBD botanical drug substance, on mucosal inflammation and hypermotility in mouse models of intestinal inflammation. Colitis was induced in mice by intracolonic administration of dinitrobenzenesulfonic acid (DNBS. Motility was evaluated in the experimental model of intestinal hypermotility induced by irritant croton oil. CBD BDS or pure CBD were given - either intraperitoneally or by oral gavage - after the inflammatory insult (curative protocol. The amounts of CBD in the colon, brain and liver after the oral treatments were measured by HPLC coupled to ion trap-time of flight mass spectrometry. CBD BDS, both when given intraperitoneally and by oral gavage, decreased the extent of the damage (as revealed by the decrease in the colon weight/length ratio and myeloperoxidase activity in the DNBS model of colitis. It also reduced intestinal hypermotility (at doses lower than those required to affect transit in healthy mice in the croton oil model of intestinal hypermotility. Under the same experimental conditions, pure CBD did not ameliorate colitis while it normalized croton oil-induced hypermotility when given intraperitoneally (in a dose-related fashion or orally (only at one dose. In conclusion, CBD BDS, given after the inflammatory insult, attenuates injury and motility in intestinal models of inflammation. These findings sustain the rationale of combining CBD with other minor Cannabis constituents and support the clinical development of CBD BDS for IBD treatment.

  13. Hydrogen-rich saline inhibits tobacco smoke-induced chronic obstructive pulmonary disease by alleviating airway inflammation and mucus hypersecretion in rats.

    Science.gov (United States)

    Liu, Zibing; Geng, Wenye; Jiang, Chuanwei; Zhao, Shujun; Liu, Yong; Zhang, Ying; Qin, Shucun; Li, Chenxu; Zhang, Xinfang; Si, Yanhong

    2017-09-01

    Chronic obstructive pulmonary disease induced by tobacco smoke has been regarded as a great health problem worldwide. The purpose of this study is to evaluate the protective effect of hydrogen-rich saline, a novel antioxidant, on chronic obstructive pulmonary disease and explore the underlying mechanism. Sprague-Dawley rats were made chronic obstructive pulmonary disease models via tobacco smoke exposure for 12 weeks and the rats were treated with 10 ml/kg hydrogen-rich saline intraperitoneally during the last 4 weeks. Lung function testing indicated hydrogen-rich saline decreased lung airway resistance and increased lung compliance and the ratio of forced expiratory volume in 0.1 s/forced vital capacity in chronic obstructive pulmonary disease rats. Histological analysis revealed that hydrogen-rich saline alleviated morphological impairments of lung in tobacco smoke-induced chronic obstructive pulmonary disease rats. ELISA assay showed hydrogen-rich saline lowered the levels of pro-inflammatory cytokines (IL-8 and IL-6) and anti-inflammatory cytokine IL-10 in bronchoalveolar lavage fluid and serum of chronic obstructive pulmonary disease rats. The content of malondialdehyde in lung tissue and serum was also determined and the data indicated hydrogen-rich saline suppressed oxidative stress reaction. The protein expressions of mucin MUC5C and aquaporin 5 involved in mucus hypersecretion were analyzed by Western blot and ELISA and the data revealed that hydrogen-rich saline down-regulated MUC5AC level in bronchoalveolar lavage fluid and lung tissue and up-regulated aquaporin 5 level in lung tissue of chronic obstructive pulmonary disease rats. In conclusion, these results suggest that administration of hydrogen-rich saline exhibits significant protective effect on chronic obstructive pulmonary disease through alleviating inflammation, reducing oxidative stress and lessening mucus hypersecretion in tobacco smoke-induced chronic obstructive pulmonary disease rats

  14. Evaluation value of intestinal flora detection for intestinal mucosal inflammation and immune response in patients with ulcerative colitis

    Directory of Open Access Journals (Sweden)

    Yan Zou

    2017-09-01

    Full Text Available Objective: To study the evaluation value of intestinal flora detection for intestinal mucosal inflammatory response and immune response in patients with ulcerative colitis. Methods: The patients who were diagnosed with ulcerative colitis in Zigong Fifth People’s Hospital between March 2015 and February 2017 were selected as the UC group, and those who were diagnosed with colonic polyps were selected as the control group. Fresh excreta were collected to detect the number of intestinal flora, and the diseased intestinal mucosa tissue was collected to detect the expression of inflammatory response molecules and immune cell transcription factors. Results: enterococcus contents in intestinal tract and TLR4, NF-kB, TNF-α, HMGB-1, T-bet and RORC mRNA expression levels in intestinal mucosa of UC group were significantly higher than those of control group while bifidobacteria contents in intestinal tract and SOCS2, SOCS3, Foxp3 and GATA-3 mRNA expression levels were significantly lower than those of control group; TLR4, NF-kB, TNF-α, HMGB-1, T-bet and RORC mRNA expression levels in intestinal mucosa of UC patients with grade II and grade III flora disturbance were significantly higher than those of UC patients with normal flora and grade I flora disturbance while SOCS2, SOCS3, Foxp3 and GATA-3 mRNA expression levels were significantly lower than those of UC patients with normal flora and grade I flora disturbance; TLR4, NF-kB, TNF-α, HMGB-1, T-bet and RORC mRNA expression levels in intestinal mucosa of UC patients with grade III flora disturbance were significantly higher than those of UC patients with grade II flora disturbance while SOCS2, SOCS3, Foxp3 and GATA-3 mRNA expression levels were significantly lower than those of UC patients with grade II flora disturbance. Conclusion: The intestinal flora disturbance in patients with ulcerative colitis can result in inflammatory response activation and immune response disorder.

  15. The bile acid sensor FXR is required for immune-regulatory activities of TLR-9 in intestinal inflammation.

    Directory of Open Access Journals (Sweden)

    Barbara Renga

    Full Text Available BACKGROUND: Toll like receptors (TLRs sense the intestinal microbiota and regulate the innate immune response. A dysregulation of TLRs function participates into intestinal inflammation. Farnesoid X Receptor (FXR is a nuclear receptor and bile acid sensor highly expressed in entero-hepatic tissues. FXR regulates lipid metabolism and innate immunity. METHODOLOGY/PRINCIPAL FINDINGS: In this study we have investigated whether FXR gene expression/function in the intestine is modulated by TLRs. We found that in human monocytes activation of membrane TLRs (i.e. TLR2, 4, 5 and 6 downregulates, while activation of intracellular TLRs (i.e. TLR3, 7, 8 and 9 upregulates the expression of FXR and its target gene SHP, small heterodimer partner. This effect was TLR9-dependent and TNFα independent. Intestinal inflammation induced in mice by TNBS downregulates the intestinal expression of FXR in a TLR9-dependent manner. Protection against TNBS colitis by CpG, a TLR-9 ligand, was lost in FXR(-/- mice. In contrast, activation of FXR rescued TLR9(-/- and MyD88(-/- mice from colitis. A putative IRF7 response element was detected in the FXR promoter and its functional characterization revealed that IRF7 is recruited on the FXR promoter under TLR9 stimulation. CONCLUSIONS/SIGNIFICANCE: Intestinal expression of FXR is selectively modulated by TLR9. In addition to its role in regulating type-I interferons and innate antiviral immunity, IRF-7 a TLR9-dependent factor, regulates the expression of FXR, linking microbiota-sensing receptors to host's immune and metabolic signaling.

  16. Dietary Bacillus subtilis-based direct-fed microbials alleviate LPS-induced intestinal immunological stress and improve intestinal barrier gene expression in commercial broiler chickens

    Science.gov (United States)

    The present study investigated the effects of B. subtilis-based probiotics on performance, modulation of host inflammatory responses and intestinal barrier integrity of broilers subjected to LPS challenge. Birds at day 0 of age were randomly allocated to one of the 3 dietary treatments - controls, ...

  17. Lactobacillus rhamnosus GG Intake Modifies Preschool Children's Intestinal Microbiota, Alleviates Penicillin-Associated Changes, and Reduces Antibiotic Use

    NARCIS (Netherlands)

    Korpela, Katri; Salonen, Anne; Virta, Lauri J.; Kumpu, Minna; Kekkonen, Riina A.; Vos, De Willem M.

    2016-01-01

    Antibiotic use is considered among the most severe causes of disturbance to children's developing intestinal microbiota, and frequently causes adverse gastrointestinal effects ranging from mild and transient diarrhoea to life- Threatening infections. Probiotics are commonly advocated to help in

  18. Dietary intervention with green dwarf banana flour (Musa sp AAA) prevents intestinal inflammation in a trinitrobenzenesulfonic acid model of rat colitis

    OpenAIRE

    Scarminio, Viviane [UNESP; Fruet, Andrea C. [UNESP; Witaicenis, Aline [UNESP; Rall, Vera L. M. [UNESP; Di Stasi, Luiz C. [UNESP

    2012-01-01

    Dietary products are among the therapeutic approaches used to modify intestinal microflora and to promote protective effects during the intestinal inflammatory process. Because the banana plant is rich in resistant starch, which is used by colonic microbiota for the anaerobic production of the short-chain fatty acids that serve as a major fuel source for colonocytes: first, green dwarf banana flour produces protective effects on the intestinal inflammation acting as a prebiotic and, second, c...

  19. [Relationship between intestinal mucosal inflammation and mental disorders in patients with irritable bowel syndrome].

    Science.gov (United States)

    Hao, Jing-xin; Han, Mai; Duan, Li-ping; Han, Ya-jing; Ge, Ying; Huang, Yue-qin

    2012-08-28

    To examine the relationship between inflammation and the comorbidity of mental disorders with irritable bowel syndrome (IBS) by comparing intestinal mucosa inflammatory biomarkers in patients with and without mental disorders. A total of 43 consecutive IBS patients fulfilling the Rome III criteria and 15 volunteers serving as controls without digestive symptoms were recruited and interviewed with Composite International Diagnostic Interview (CIDI) by the well-trained staff and thus classified as with or without mental disorders. All subjects underwent colonoscopy and biopsies were acquired from the mucosa of distal ileum and colon. CD3(+) lymphocytes, mast cells, 5-HT positive cells and (indoleamine 2,3-dioxygenase) IDO positive cells were identified immunohistologically in mucosa biopsies in volunteers (n = 13), IBS patients without mental disorder (n = 24) and IBS patients with mental disorder (n = 19). The incidence of mental disorders in IBS patients was significantly higher than that in the volunteers (19/43 vs 2/15, P = 0.012), including 9 patients with anxiety disorders and 8 with mood disorders. (1) The number of mast cells in IBS patients with mental disorder and that in IBS patients without mental disorder has no statistical significance ((16.7 ± 3.6)/HP vs (15.4 ± 3.1)/HP in distal ileum, (12.8 ± 2.2)/HP vs (12.3 ± 2.5)/HP in sigmoid, both P > 0.05). Similar results were seen in 5-HT positive cells ((3.7 ± 0.9)/HP vs (3.4 ± 0.8)/HP in distal ileum, (6.1 ± 1.8)/HP vs (5.2 ± 1.8)/HP in sigmoid, both P > 0.05). In distal ileum, the number of CD3(+) cells in IBS patients with mental disorder has no statistical significance with that in the IBS patients without mental disorder ((62 ± 16)/HP vs (55 ± 22)/HP, P > 0.05). Similar results were seen in IDO positive cells (6(2, 8)/HP vs 2(1, 5)/HP, P > 0.05). (2) The number of IDO positive cells from distal ileum in IBS patients with anxiety disorder was significantly higher than that in the IBS patients

  20. Simvastatin alleviates airway inflammation and remodelling through up-regulation of autophagy in mouse models of asthma.

    Science.gov (United States)

    Gu, Wen; Cui, Rong; Ding, Tao; Li, Xiaoming; Peng, Juan; Xu, Weiguo; Han, Fengfeng; Guo, Xuejun

    2017-04-01

    Statins have been widely used in inflammatory diseases including asthma, because of their anti-inflammatory and immunomodulatory properties. It has been shown that simvastatin induces autophagy and cell death in some circumstances. However, the possible cross-talk between simvastatin and autophagic processes in lung disease is largely unknown. Thus, we investigated the impact of simvastatin on airway inflammation and airway remodelling and the possible relationship of these processes to a simvastatin-induced autophagic pathway in mouse models of asthma. Ovalbumin (OVA)-sensitized and challenged mice were treated with simvastatin and sacrificed. The autophagy-related proteins Atg5, LC3B and Beclin1 were quantified, as well as the autophagy flux in bronchial smooth muscle cells (BSMCs). The relationship between airway inflammation and the autophagic process was investigated. We show that simvastatin treatment mediates activation of autophagy in BSMCs, which is correlated with airway inflammation and airway remodelling in mouse models of asthma. Simvastatin increases autophagy-related protein Atg5, LC3B and Beclin1 expression and autophagosome formation in lung tissue. Simvastatin-induced autophagy is associated with increased interferon-gamma (IFN-γ) and decreased IL-4, IL-5 and IL-13 cytokines production in BSMCs, as well as reversed extracellular matrix (ECM) deposition. In contrast, autophagy inhibitor 3-methyladenine (3-MA) eliminates the therapeutic effect of simvastatin. These findings demonstrate that simvastatin inhibits airway inflammation and airway remodelling through an activated autophagic process in BSMCs. We propose a crucial function of autophagy in statin-based therapeutic approaches in asthma. © 2016 Asian Pacific Society of Respirology.

  1. Hymenaea stigonocarpa Mart. ex Hayne: A tropical medicinal plant with intestinal anti-inflammatory activity in TNBS model of intestinal inflammation in rats.

    Science.gov (United States)

    Orsi, Patrícia Rodrigues; Seito, Leonardo Noboru; Di Stasi, Luiz Claudio

    2014-01-01

    Stem bark and fruit pulp of Hymenaea stigonocarpa Mart ex. Hayne (Fabaceae) has been popularly used to treat inflammation and gastrointestinal diseases including ulcers, diarrhea and gastric pain. The aim of this study was to investigate the intestinal anti-inflammatory activity of a methanol extract derived from the stem bark and diet with fruit pulp of Hymenaea stigonocarpa in the TNBS model of intestinal inflammation in rats. The intestinal anti-inflammatory activity of stem bark extract (100, 200 and 400mg/kg) and fruit pulp (10% and 5% in diet) was measured against the intestinal inflammatory process induced by TNBS (trinitrobenzesulphonic acid) in rats. The protective effects were evaluated as follows: evaluation of intestinal damage (damage score, extension of lesion, colon weight/length ratio), incidence of diarrhea and adherence to adjacent organs, colon glutathione (GSH) and malondialdehyde (MDA) contents, myeloperoxidase (MPO) and alkaline phosphatase (AP) activities. In addition, in vitro studies on lipid peroxidation in rat brain membranes and phytochemical profile were performed with both stem bark and fruit pulp. Treatment with 100, 200 and 400mg/kg of stem bark extract and 10% fruit pulp flour showed protective effects in the TNBS-induced colon damage, which was related to inhibition of MPO and AP activities, reduction in colon MDA content, and counteraction of GSH depletion induced by inflammatory process. A concentration-dependent inhibitory effect on the lipid peroxidation in rat brain membranes for stem bark and fruit pulp was determined, with an IC50 value of 5.25 ± 0.23 μg/mL and 27.33 ± 0.09 μg/mL, respectively. Similar phytochemical composition was observed in fruit and stem bark, including mainly flavonoids, condensed tannins and terpenes. Stem bark extract and fruit pulp flour of Hymenaea stigonocarpa prevented TNBS-induced colonic damage in rats and this protective effect were associated to an improvement of intestinal oxidative

  2. Administration of Protein kinase D1 induce an immunomodulatory effect on lipopolysaccharide-induced intestinal inflammation in a co-culture model of intestinal epithelial Caco-2 cells and RAW 264.7 macrophage cells

    DEFF Research Database (Denmark)

    Nielsen, Ditte Søvsø Gundelund; Fredborg, Marlene; Andersen, Vibeke

    2017-01-01

    the effects of human PKD1 in relation to intestinal inflammation, using a co-culture model of intestinal epithelial Caco-2 cells and RAW264.7 macrophages. An inflammatory response was induced in the macrophages by lipopolysaccharide (LPS), upregulating the expression of tumour necrosis factor alpha (TNF......-α), interleukin- (IL-) 1β, and IL-6 besides increasing the secretion of TNF-α protein. The effect of administering PKD1 to Caco-2 was evaluated in relation to both amelioration of inflammation and the ability to suppress inflammation initiation. Administration of PKD1 (10–100 ng/ml) following induction...

  3. Evidence for a dual function of monocyte-derived mononuclear phagocytes during chronic intestinal inflammation

    DEFF Research Database (Denmark)

    Rivollier, Aymeric Marie Christian; Pool, Lieneke; Frising, Ulrika

    Mononuclear phagocytes derived from tissue-infiltrating monocytes play diverse roles in immunity, ranging from pathogen killing to immune regulation. We and others showed that, upon recruitment to the intestinal mucosa, the differentiation of Ly6Chi monocytes into phagocytes with anti- versus pro...... cells pool in the inflamed intestinal mucosa. However, surprisingly, mice deficient for the chemokine receptor CCR2, which exhibit highly decreased amounts of intestinal MDP, develop an intestinal pathology similar to their wild type littermates. Preliminary experiments using the anti-CD40 colitis model...

  4. Benzo(a)pyrene-induced pulmonary inflammation, edema, surfactant dysfunction, and injuries in rats: alleviation by farnesol.

    Science.gov (United States)

    Qamar, Wajhul; Khan, Abdul Quaiyoom; Khan, Rehan; Lateef, Abdul; Tahir, Mir; Rehman, Muneeb U; Ali, Farrah; Sultana, Sarwat

    2012-02-01

    Benzo(a)pyrene (B(a)P) is a well-known environmental contaminant and carcinogen. Its sources include tobacco smoke, automobile exhaust, forest fire, and other combustion processes. Farnesol, an active principle of Vachellia farnesiana and other aromatic plants, possesses preventive properties against various toxicities. Present study was designed to estimate chemopreventive effects of farnesol against B(a)P-induced pulmonary injuries. To determine the protective effects of farnesol, it was administered orally at 2 doses (100 and 200 mg/kg body weight [b.w.]) once daily for 14 days. Rats were exposed intratracheally to B(a)P, 5 mg/kg b.w. on days 12 and 14, thereafter assessed for pulmonary toxicities 24 hours post last dose of B(a)P. B(a)P-induced edema, inflammation, oxidative stress, and consequent damages in lungs were assessed in terms of total protein, total cell count, nitric oxide (NO), lactate dehydrogenase (LDH), alkaline phosphatase, and in bronchoalveolar lavage fluid (BALF). B(a)P also reduced the levels of phospholipids (lung surfactants) in BALF. However, pretreatment with farnesol at both the doses significantly reduced the lung injuries and inflammatory responses. Farnesol also protected the levels of phospholipids to normal when compared with control. It also modified the activities of B(a)P metabolizing enzymes NADPH-cytochrome P450 reductase, microsomal epoxide hydrolase (mEH), and glutathione S-transferase (GST) in lung tissue of rats. Present findings suggest a prominent role of farnesol against B(a)P-induced lung inflammation, edema, surfactant dysfunction, and epithelial damages in Wistar rats. In conclusion, farnesol shows lung protection against B(a)P toxicities in Wistar rats.

  5. Butyrate Attenuates Lipopolysaccharide-Induced Inflammation in Intestinal Cells and Crohn's Mucosa through Modulation of Antioxidant Defense Machinery

    Science.gov (United States)

    Russo, Ilaria; Luciani, Alessandro; De Cicco, Paola; Troncone, Edoardo; Ciacci, Carolina

    2012-01-01

    Oxidative stress plays an important role in the pathogenesis of inflammatory bowel disease (IBD), including Crohn's disease (CrD). High levels of Reactive Oxygen Species (ROS) induce the activation of the redox-sensitive nuclear transcription factor kappa-B (NF-κB), which in turn triggers the inflammatory mediators. Butyrate decreases pro-inflammatory cytokine expression by the lamina propria mononuclear cells in CrD patients via inhibition of NF-κB activation, but how it reduces inflammation is still unclear. We suggest that butyrate controls ROS mediated NF-κB activation and thus mucosal inflammation in intestinal epithelial cells and in CrD colonic mucosa by triggering intracellular antioxidant defense systems. Intestinal epithelial Caco-2 cells and colonic mucosa from 14 patients with CrD and 12 controls were challenged with or without lipopolysaccaride from Escherichia Coli (EC-LPS) in presence or absence of butyrate for 4 and 24 h. The effects of butyrate on oxidative stress, p42/44 MAP kinase phosphorylation, p65-NF-κB activation and mucosal inflammation were investigated by real time PCR, western blot and confocal microscopy. Our results suggest that EC-LPS challenge induces a decrease in Gluthation-S-Transferase-alpha (GSTA1/A2) mRNA levels, protein expression and catalytic activity; enhanced levels of ROS induced by EC-LPS challenge mediates p65-NF-κB activation and inflammatory response in Caco-2 cells and in CrD colonic mucosa. Furthermore butyrate treatment was seen to restore GSTA1/A2 mRNA levels, protein expression and catalytic activity and to control NF-κB activation, COX-2, ICAM-1 and the release of pro-inflammatory cytokine. In conclusion, butyrate rescues the redox machinery and controls the intracellular ROS balance thus switching off EC-LPS induced inflammatory response in intestinal epithelial cells and in CrD colonic mucosa. PMID:22412931

  6. Rho-A prenylation and signaling link epithelial homeostasis to intestinal inflammation

    DEFF Research Database (Denmark)

    López-Posadas, Rocío; Becker, Christoph; Günther, Claudia

    2016-01-01

    Although defects in intestinal barrier function are a key pathogenic factor in patients with inflammatory bowel diseases (IBDs), the molecular pathways driving disease-specific alterations of intestinal epithelial cells (IECs) are largely unknown. Here, we addressed this issue by characterizing t...

  7. VSL#3 Probiotic Upregulates Intestinal Mucosal Alkaline Sphingomyelinase and Reduces Inflammation

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    Isaac Soo

    2008-01-01

    Full Text Available BACKGROUND: Alkaline sphingomyelinase, an enzyme found exclusively in bile and the intestinal brush border, hydrolyzes sphingomyelin into ceramide, sphingosine and sphingosine-1-phosphate, thereby inducing epithelial apoptosis. Reduced levels of alkaline sphingomyelinase have been found in premalignant and malignant intestinal epithelia and in ulcerative colitis tissue. Probiotic bacteria can be a source of sphingomyelinase.

  8. Umbilical cord-derived mesenchymal stem cells alleviated inflammation and inhibited apoptosis in interstitial cystitis via AKT/mTOR signaling pathway.

    Science.gov (United States)

    Xie, Juncong; Liu, Bolong; Chen, Jialiang; Xu, Yuancheng; Zhan, Hailun; Yang, Fei; Li, Wenbiao; Zhou, Xiangfu

    2018-01-01

    Interstitial cystitis (IC) is a bladder syndrome characterized by pelvic pain and urinary frequency without infection or other identifiable pathology. There are no effective treatments to cure IC. This study investigated the effects of human umbilical cord-derived mesenchymal stem cells (UC-MSCs) injection on IC rat model. Furthermore, we used a coculture system to find the possible molecular mechanism on the human uroepithelial cells (SV-HUC-1), which was the cell model of IC. A rat model of IC was established via systemic injection with cyclophosphamide (CYP) and a cell model of IC was induced by being exposed to tumor necrosis factor (TNF)-α (10 ng/ml). After one week, UC-MSCs injection significantly ameliorated the bladder voiding function in IC rat model. And the Histo- and immunohistochemical analyses showed that UC-MSCs can repair impaired bladder, reduce mast cell infiltration and inhibit apoptosis of urothelium. ELISA results showed that UC-MSCs can decrease IL-1β, IL-6 and TNF-α in bladder. In the coculture system, UC-MSCs can promote proliferation of impaired SV-HUC-1 cells, and inhibit apoptosis. However, while knocked down EGF secreted by UC-MSCs with siRNA, the effects would be weaken. Western blot showed that UC-MSCs increase protein expression levels of p-AKT and p-mTOR in SV-HUC-1 cells, and decrease the levels of cleaved caspase-3. Taken together, we provide evidence that UC-MSCs therapy can successfully alleviate IC in a preclinical animal Model and cell model by alleviating inflammation, promoting proliferation and inhibiting apoptosis. In addition, we demonstrate that the AKT/mTOR signaling pathway was activated. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Orally administered Taenia solium Calreticulin prevents experimental intestinal inflammation and is associated with a type 2 immune response.

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    Fela Mendlovic

    Full Text Available Intestinal helminth antigens are inducers of type 2 responses and can elicit regulatory immune responses, resulting in dampened inflammation. Several platyhelminth proteins with anti-inflammatory activity have been reported. We have identified, cloned and expressed the Taenia solium calreticulin (rTsCRT and shown that it predominantly induces a type 2 response characterized by IgG1, IL-4 and IL-5 production in mice. Here, we report the rTsCRT anti-inflammatory activity in a well-known experimental colitis murine model. Mice were orally immunized with purified rTsCRT and colitis was induced with trinitrobenzene sulfonic acid (TNBS. Clinical signs of disease, macroscopic and microscopic tissue inflammation, cytokine production and micronuclei formation, as a marker of genotoxicity, were measured in order to assess the effect of rTsCRT immunization on experimentally induced colitis. rTsCRT administration prior to TNBS instillation significantly reduced the inflammatory parameters, including the acute phase cytokines TNF-α, IL-1β and IL-6. Dampened inflammation was associated with increased local expression of IL-13 and systemic IL-10 and TGF-β production. Genotoxic damage produced by the inflammatory response was also precluded. Our results show that oral treatment with rTsCRT prevents excessive TNBS-induced inflammation in mice and suggest that rTsCRT has immunomodulatory properties associated with the expression of type 2 and regulatory cytokines commonly observed in other helminths.

  10. Anthocyanin-Rich Extract from Red Chinese Cabbage Alleviates Vascular Inflammation in Endothelial Cells and Apo E−/− Mice

    Directory of Open Access Journals (Sweden)

    Hee Kyoung Joo

    2018-03-01

    Full Text Available Anthocyanins, the most prevalent flavonoids in red/purple fruits and vegetables, are known to improve immune responses and reduce chronic disease risks. In this study, the anti-inflammatory activities of an anthocyanin-rich extract from red Chinese cabbage (ArCC were shown based on its inhibitory effects in cultured endothelial cells and hyperlipidemic apolipoprotein E-deficient mice. ArCC treatment suppressed monocyte adhesion to tumor necrosis factor-α-stimulated endothelial cells. This was validated by ArCC’s ability to downregulate the expression and transcription of endothelial adhesion molecules, determined by immunoblot and luciferase promoter assays, respectively. The regulation of adhesion molecules was accompanied by transcriptional inhibition of nuclear factor-κB, which restricted cytoplasmic localization as shown by immunocytochemistry. Administration of ArCC (150 or 300 mg/kg/day inhibited aortic inflammation in hyperlipidemic apolipoprotein E-deficient mice, as shown by in vivo imaging. Immunohistochemistry and plasma analysis showed that the aortas from these mice exhibited markedly lower leukocyte infiltration, reduced plaque formation, and lower concentrations of blood inflammatory cytokines than those observed in the control mice. The results suggest that the consumption of anthocyanin-rich red Chinese cabbage is closely correlated with lowering the risk of vascular inflammatory diseases.

  11. Soybean β-conglycinin induces inflammation and oxidation and causes dysfunction of intestinal digestion and absorption in fish.

    Science.gov (United States)

    Zhang, Jin-Xiu; Guo, Lin-Ying; Feng, Lin; Jiang, Wei-Dan; Kuang, Sheng-Yao; Liu, Yang; Hu, Kai; Jiang, Jun; Li, Shu-Hong; Tang, Ling; Zhou, Xiao-Qiu

    2013-01-01

    β-Conglycinin has been identified as one of the major feed allergens. However, studies of β-conglycinin on fish are scarce. This study investigated the effects of β-conglycinin on the growth, digestive and absorptive ability, inflammatory response, oxidative status and gene expression of juvenile Jian carp (Cyprinus carpio var. Jian) in vivo and their enterocytes in vitro. The results indicated that the specific growth rate (SGR), feed intake, and feed efficiency were reduced by β-conglycinin. In addition, activities of trypsin, chymotrypsin, lipase, creatine kinase, Na(+),K(+)-ATPase and alkaline phosphatase in the intestine showed similar tendencies. The protein content of the hepatopancreas and intestines, and the weight and length of the intestines were all reduced by β-conglycinin. β-Conglycinin increased lipid and protein oxidation in the detected tissues and cells. However, β-conglycinin decreased superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), glutathione peroxidase (GPx) and glutathione reductase (GR) activities and glutathione (GSH) content in the intestine and enterocytes. Similar antioxidant activity in the hepatopancreas was observed, except for GST. The expression of target of rapamycin (TOR) gene was reduced by β-conglycinin. Furthermore, mRNA levels of interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), and transforming growth factor-β (TGF-β) genes were increased by β-conglycinin. However, β-conglycinin increased CuZnSOD, MnSOD, CAT, and GPx1b gene expression. In conclusion, this study indicates that β-conglycinin induces inflammation and oxidation, and causes dysfunction of intestinal digestion and absorption in fish, and finally reduces fish growth. The results of this study provide some information to the mechanism of β-conglycinin-induced negative effects.

  12. Soybean β-conglycinin induces inflammation and oxidation and causes dysfunction of intestinal digestion and absorption in fish.

    Directory of Open Access Journals (Sweden)

    Jin-Xiu Zhang

    Full Text Available β-Conglycinin has been identified as one of the major feed allergens. However, studies of β-conglycinin on fish are scarce. This study investigated the effects of β-conglycinin on the growth, digestive and absorptive ability, inflammatory response, oxidative status and gene expression of juvenile Jian carp (Cyprinus carpio var. Jian in vivo and their enterocytes in vitro. The results indicated that the specific growth rate (SGR, feed intake, and feed efficiency were reduced by β-conglycinin. In addition, activities of trypsin, chymotrypsin, lipase, creatine kinase, Na(+,K(+-ATPase and alkaline phosphatase in the intestine showed similar tendencies. The protein content of the hepatopancreas and intestines, and the weight and length of the intestines were all reduced by β-conglycinin. β-Conglycinin increased lipid and protein oxidation in the detected tissues and cells. However, β-conglycinin decreased superoxide dismutase (SOD, catalase (CAT, glutathione-S-transferase (GST, glutathione peroxidase (GPx and glutathione reductase (GR activities and glutathione (GSH content in the intestine and enterocytes. Similar antioxidant activity in the hepatopancreas was observed, except for GST. The expression of target of rapamycin (TOR gene was reduced by β-conglycinin. Furthermore, mRNA levels of interleukin-8 (IL-8, tumor necrosis factor-α (TNF-α, and transforming growth factor-β (TGF-β genes were increased by β-conglycinin. However, β-conglycinin increased CuZnSOD, MnSOD, CAT, and GPx1b gene expression. In conclusion, this study indicates that β-conglycinin induces inflammation and oxidation, and causes dysfunction of intestinal digestion and absorption in fish, and finally reduces fish growth. The results of this study provide some information to the mechanism of β-conglycinin-induced negative effects.

  13. Progesterone Alleviates Endometriosis via Inhibition of Uterine Cell Proliferation, Inflammation and Angiogenesis in an Immunocompetent Mouse Model

    Science.gov (United States)

    Kannan, Athilakshmi; Davila, Juanmahel; Zhao, Yuechao; Nowak, Romana A.; Bagchi, Milan K.; Bagchi, Indrani C.; Li, Quanxi

    2016-01-01

    Endometriosis, defined as growth of the endometrial cells outside the uterus, is an inflammatory disorder that is associated with chronic pelvic pain and infertility in women of childbearing age. Although the estrogen-dependence of endometriosis is well known, the role of progesterone in development of this disease remains poorly understood. In this study, we developed a disease model in which endometriosis was induced in the peritoneal cavities of immunocompetent female mice, and maintained with exogenous estrogen. The endometriosis-like lesions that were identified at a variety of ectopic locations exhibited abundant blood supply and extensive adhesions. Histological examination revealed that these lesions had a well-organized endometrial architecture and fibrotic response, resembling those recovered from clinical patients. In addition, an extensive proliferation, inflammatory response, and loss of estrogen receptor alpha (ERα) and progesterone receptor (PR) expression were also observed in these lesions. Interestingly, administration of progesterone before, but not after, lesion induction suppressed lesion expansion and maintained ERα and PR expressions. These progesterone-pretreated lesions exhibited attenuation in KI67, CD31, and pro-inflammatory cytokine expression as well as macrophage infiltration, indicating that progesterone ameliorates endometriosis progression by inhibiting cell proliferation, inflammation and neovascularization. Our studies further showed that suppression of global DNA methylation by application of DNA methyltransferase inhibitor to female mice bearing ectopic lesions restrained lesion expansion and restored ERα and PR expression in eutopic endometrium and ectopic lesions. These results indicate that epigenetic regulation of target gene expression via DNA methylation contributes, at least in part, to progesterone resistance in endometriosis. PMID:27776183

  14. Progesterone Alleviates Endometriosis via Inhibition of Uterine Cell Proliferation, Inflammation and Angiogenesis in an Immunocompetent Mouse Model.

    Directory of Open Access Journals (Sweden)

    Yanfen Li

    Full Text Available Endometriosis, defined as growth of the endometrial cells outside the uterus, is an inflammatory disorder that is associated with chronic pelvic pain and infertility in women of childbearing age. Although the estrogen-dependence of endometriosis is well known, the role of progesterone in development of this disease remains poorly understood. In this study, we developed a disease model in which endometriosis was induced in the peritoneal cavities of immunocompetent female mice, and maintained with exogenous estrogen. The endometriosis-like lesions that were identified at a variety of ectopic locations exhibited abundant blood supply and extensive adhesions. Histological examination revealed that these lesions had a well-organized endometrial architecture and fibrotic response, resembling those recovered from clinical patients. In addition, an extensive proliferation, inflammatory response, and loss of estrogen receptor alpha (ERα and progesterone receptor (PR expression were also observed in these lesions. Interestingly, administration of progesterone before, but not after, lesion induction suppressed lesion expansion and maintained ERα and PR expressions. These progesterone-pretreated lesions exhibited attenuation in KI67, CD31, and pro-inflammatory cytokine expression as well as macrophage infiltration, indicating that progesterone ameliorates endometriosis progression by inhibiting cell proliferation, inflammation and neovascularization. Our studies further showed that suppression of global DNA methylation by application of DNA methyltransferase inhibitor to female mice bearing ectopic lesions restrained lesion expansion and restored ERα and PR expression in eutopic endometrium and ectopic lesions. These results indicate that epigenetic regulation of target gene expression via DNA methylation contributes, at least in part, to progesterone resistance in endometriosis.

  15. Human milk oligosaccharide effects on intestinal function and inflammation after preterm birth in pigs

    DEFF Research Database (Denmark)

    Rasmussen, Stine O.; Martin, Lena; Østergaard, Mette V.

    2017-01-01

    Human milk oligosaccharides (HMOs) may mediate prebiotic and anti-inflammatory effects in newborns. This is particularly important for preterm infants who are highly susceptible to intestinal dysfunction and necrotizing enterocolitis (NEC). We hypothesized that HMO supplementation of infant formu...

  16. Effects of zeolite supplementation on parameters of intestinal barrier integrity, inflammation, redoxbiology and performance in aerobically trained subjects.

    Science.gov (United States)

    Lamprecht, Manfred; Bogner, Simon; Steinbauer, Kurt; Schuetz, Burkhard; Greilberger, Joachim F; Leber, Bettina; Wagner, Bernhard; Zinser, Erwin; Petek, Thomas; Wallner-Liebmann, Sandra; Oberwinkler, Tanja; Bachl, Norbert; Schippinger, Gert

    2015-01-01

    Zeolites are crystalline compounds with microporous structures of Si-tetrahedrons. In the gut, these silicates could act as adsorbents, ion-exchangers, catalysts, detergents or anti-diarrheic agents. This study evaluated whether zeolite supplementation affects biomarkers of intestinal wall permeability and parameters of oxidation and inflammation in aerobically trained individuals, and whether it could improve their performance. In a randomized, double-blinded, placebo controlled trial, 52 endurance trained men and women, similar in body fat, non-smokers, 20-50 years, received 1.85 g of zeolite per day for 12 weeks. Stool samples for determination of intestinal wall integrity biomarkers were collected. From blood, markers of redox biology, inflammation, and DNA damage were determined at the beginning and the end of the study. In addition, VO2max and maximum performance were evaluated at baseline and after 12 weeks of treatment. For statistical analyses a 2-factor ANOVA was used. At baseline both groups showed slightly increased stool zonulin concentrations above normal. After 12 weeks with zeolite zonulin was significantly (p zonulin. This was accompanied by mild anti-inflammatory effects in this cohort of aerobically trained subjects. Further research is needed to explore mechanistic explanations for the observations in this study.

  17. Western diet induces a shift in microbiota composition enhancing susceptibility to Adherent-Invasive E. coli infection and intestinal inflammation.

    Science.gov (United States)

    Agus, Allison; Denizot, Jérémy; Thévenot, Jonathan; Martinez-Medina, Margarita; Massier, Sébastien; Sauvanet, Pierre; Bernalier-Donadille, Annick; Denis, Sylvain; Hofman, Paul; Bonnet, Richard; Billard, Elisabeth; Barnich, Nicolas

    2016-01-08

    Recent advances have shown that the abnormal inflammatory response observed in CD involves an interplay among intestinal microbiota, host genetics and environmental factors. The escalating consumption of fat and sugar in Western countries parallels an increased incidence of CD during the latter 20(th) century. The impact of a HF/HS diet in mice was evaluated for the gut micro-inflammation, intestinal microbiota composition, function and selection of an E. coli population. The HF/HS diet created a specific inflammatory environment in the gut, correlated with intestinal mucosa dysbiosis characterized by an overgrowth of pro-inflammatory Proteobacteria such as E. coli, a decrease in protective bacteria, and a significantly decreased of SCFA concentrations. The expression of GPR43, a SCFA receptor was reduced in mice treated with a HF/HS diet and reduced in CD patients compared with controls. Interestingly, mice treated with an agonist of GPR43 were protected against DSS-induced colitis. Finally, the transplantation of feces from HF/HS treated mice to GF mice increased susceptibility to AIEC infection. Together, our results demonstrate that a Western diet could aggravate the inflammatory process and that the activation of the GPR43 receptor pathway could be used as a new strategy to treat CD patients.

  18. Environmental factors regulate Paneth cell phenotype and host susceptibility to intestinal inflammation in Irgm1-deficient mice

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    Allison R. Rogala

    2018-02-01

    Full Text Available Crohn's disease (CD represents a chronic inflammatory disorder of the intestinal tract. Several susceptibility genes have been linked to CD, though their precise role in the pathogenesis of this disorder remains unclear. Immunity-related GTPase M (IRGM is an established risk allele in CD. We have shown previously that conventionally raised (CV mice lacking the IRGM ortholog, Irgm1 exhibit abnormal Paneth cells (PCs and increased susceptibility to intestinal injury. In the present study, we sought to utilize this model system to determine if environmental conditions impact these phenotypes, as is thought to be the case in human CD. To accomplish this, wild-type and Irgm1−/− mice were rederived into specific pathogen-free (SPF and germ-free (GF conditions. We next assessed how these differential housing environments influenced intestinal injury patterns, and epithelial cell morphology and function in wild-type and Irgm1−/− mice. Remarkably, in contrast to CV mice, SPF Irgm1−/− mice showed only a slight increase in susceptibility to dextran sodium sulfate-induced inflammation. SPF Irgm1−/− mice also displayed minimal abnormalities in PC number and morphology, and in antimicrobial peptide expression. Goblet cell numbers and epithelial proliferation were also unaffected by Irgm1 in SPF conditions. No microbial differences were observed between wild-type and Irgm1−/− mice, but gut bacterial communities differed profoundly between CV and SPF mice. Specifically, Helicobacter sequences were significantly increased in CV mice; however, inoculating SPF Irgm1−/− mice with Helicobacter hepaticus was not sufficient to transmit a pro-inflammatory phenotype. In summary, our findings suggest the impact of Irgm1-deficiency on susceptibility to intestinal inflammation and epithelial function is critically dependent on environmental influences. This work establishes the importance of Irgm1−/− mice as a model to elucidate host

  19. Cirrhosis induced by bile duct ligation alleviates acetic acid intestinal damages in rats: Involvements of nitrergic and opioidergic systems.

    Science.gov (United States)

    Rahimi, Nastaran; Hassanipour, Mahsa; Allahabadi, Narges Sistany; Sabbaghziarani, Fatemeh; Yazdanparast, Maryam; Dehpour, Ahmadreza

    2017-11-22

    Colitis, a colonic inflammatory condition, showed a linkage with hepatobiliary disorders such as cirrhosis. It has been reported that both endogenous opioids and nitric oxide (NO) play critical roles in colitis pathogenesis. Moreover, opioid and NO levels showed elevation in patients with cirrhosis. The aim of this study was to evaluate the effect of cirrhosis on the experimental model of colitis and the possible involvement of opioidergic/nitrergic systems in rats. Colitis was induced by acetic acid 28 days after bile duct ligation (BDL). L-NAME, as an inhibitor of NO synthase and naltrexone, as an antagonist of opioid receptors were administered intraperitoneally to animals during 3 days after induction of colitis. Macroscopic colitis lesion area, inflammatory mediators change, NO metabolite levels, and colon microscopic injuries were assessed 3 days after induction. Cirrhosis significantly reduced the severity of damages to the colon. Administration of L-NAME (10 mg/kg), naltrexone (10 mg/kg) and co-administration of L-NAME (1 mg/kg) and naltrexone (5 mg/kg) significantly decreased the protective effect of BDL on colitis. Nitrite elevated levels in BDL rats were significantly diminished in L-NAME- and naltrexone-treated animals. Histopathology parameters and cytokines level alterations in the colon of acetic acid-treated animals after BDL was reversed after injection of L-NAME, naltrexone, and co-administration of L-NAME (1 mg/kg) + naltrexone (5 mg/kg). Cirrhosis improved the intestinal damages induced by acetic acid in rats which may be mediated through interaction of nitrergic and opioidergic systems. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.

  20. Bacterial Signaling at the Intestinal Epithelial Interface in Inflammation and Cancer

    Directory of Open Access Journals (Sweden)

    Olivia I. Coleman

    2018-01-01

    Full Text Available The gastrointestinal (GI tract provides a compartmentalized interface with an enormous repertoire of immune and metabolic activities, where the multicellular structure of the mucosa has acquired mechanisms to sense luminal factors, such as nutrients, microbes, and a variety of host-derived and microbial metabolites. The GI tract is colonized by a complex ecosystem of microorganisms, which have developed a highly coevolved relationship with the host’s cellular and immune system. Intestinal epithelial pattern recognition receptors (PRRs substantially contribute to tissue homeostasis and immune surveillance. The role of bacteria-derived signals in intestinal epithelial homeostasis and repair has been addressed in mouse models deficient in PRRs and signaling adaptors. While critical for host physiology and the fortification of barrier function, the intestinal microbiota poses a considerable health challenge. Accumulating evidence indicates that dysbiosis is associated with the pathogenesis of numerous GI tract diseases, including inflammatory bowel diseases (IBD and colorectal cancer (CRC. Aberrant signal integration at the epithelial cell level contributes to such diseases. An increased understanding of bacterial-specific structure recognition and signaling mechanisms at the intestinal epithelial interface is of great importance in the translation to future treatment strategies. In this review, we summarize the growing understanding of the regulation and function of the intestinal epithelial barrier, and discuss microbial signaling in the dynamic host–microbe mutualism in both health and disease.

  1. ILC3 GM-CSF production and mobilisation orchestrate acute intestinal inflammation.

    Science.gov (United States)

    Pearson, Claire; Thornton, Emily E; McKenzie, Brent; Schaupp, Anna-Lena; Huskens, Nicky; Griseri, Thibault; West, Nathaniel; Tung, Sim; Seddon, Benedict P; Uhlig, Holm H; Powrie, Fiona

    2016-01-18

    Innate lymphoid cells (ILCs) contribute to host defence and tissue repair but can induce immunopathology. Recent work has revealed tissue-specific roles for ILCs; however, the question of how a small population has large effects on immune homeostasis remains unclear. We identify two mechanisms that ILC3s utilise to exert their effects within intestinal tissue. ILC-driven colitis depends on production of granulocyte macrophage-colony stimulating factor (GM-CSF), which recruits and maintains intestinal inflammatory monocytes. ILCs present in the intestine also enter and exit cryptopatches in a highly dynamic process. During colitis, ILC3s mobilize from cryptopatches, a process that can be inhibited by blocking GM-CSF, and mobilization precedes inflammatory foci elsewhere in the tissue. Together these data identify the IL-23R/GM-CSF axis within ILC3 as a key control point in the accumulation of innate effector cells in the intestine and in the spatio-temporal dynamics of ILCs in the intestinal inflammatory response.

  2. Nopal feeding reduces adiposity, intestinal inflammation and shifts the cecal microbiota and metabolism in high-fat fed rats.

    Science.gov (United States)

    Moran-Ramos, Sofia; He, Xuan; Chin, Elizabeth L; Tovar, Armando R; Torres, Nimbe; Slupsky, Carolyn M; Raybould, Helen E

    2017-01-01

    Nopal is a cactus plant widely consumed in Mexico that has been used in traditional medicine to aid in the treatment of type-2 diabetes. We previously showed that chronic consumption of dehydrated nopal ameliorated hepatic steatosis in obese (fa/fa) rats; however, description of the effects on other tissues is sparse. The aim of the present study was to investigate the effects of nopal cladode consumption on intestinal physiology, microbial community structure, adipose tissue, and serum biochemistry in diet-induced obese rats. Rats were fed either a normal fat (NF) diet or a HF diet containing 4% of dietary fiber from either nopal or cellulose for 6 weeks. Consumption of nopal counteracted HF-induced adiposity and adipocyte hypertrophy, and induced profound changes in intestinal physiology. Nopal consumption reduced biomarkers of intestinal inflammation (mRNA expression of IL-6) and oxidative stress (ROS), modfied gut microbiota composition, increasing microbial diversity and cecal fermentation (SCFA), and altered the serum metabolome. Interestingly, metabolomic analysis of dehydrated nopal revealed a high choline content, which appeared to generate high levels of serum betaine, that correlated negatively with hepatic triglyceride (TAG) levels. A parallel decrease in some of the taxa associated with the production of trimethylamine, suggest an increase in choline absorption and bioavailability with transformation to betaine. The latter may partially explain the previously observed effect of nopal on the development of hepatic steatosis. In conclusion, this study provides new evidence on the effects of nopal consumption on normal and HF-diet induced changes in the intestine, the liver and systemic metabolism.

  3. Nopal feeding reduces adiposity, intestinal inflammation and shifts the cecal microbiota and metabolism in high-fat fed rats.

    Directory of Open Access Journals (Sweden)

    Sofia Moran-Ramos

    Full Text Available Nopal is a cactus plant widely consumed in Mexico that has been used in traditional medicine to aid in the treatment of type-2 diabetes. We previously showed that chronic consumption of dehydrated nopal ameliorated hepatic steatosis in obese (fa/fa rats; however, description of the effects on other tissues is sparse. The aim of the present study was to investigate the effects of nopal cladode consumption on intestinal physiology, microbial community structure, adipose tissue, and serum biochemistry in diet-induced obese rats. Rats were fed either a normal fat (NF diet or a HF diet containing 4% of dietary fiber from either nopal or cellulose for 6 weeks. Consumption of nopal counteracted HF-induced adiposity and adipocyte hypertrophy, and induced profound changes in intestinal physiology. Nopal consumption reduced biomarkers of intestinal inflammation (mRNA expression of IL-6 and oxidative stress (ROS, modfied gut microbiota composition, increasing microbial diversity and cecal fermentation (SCFA, and altered the serum metabolome. Interestingly, metabolomic analysis of dehydrated nopal revealed a high choline content, which appeared to generate high levels of serum betaine, that correlated negatively with hepatic triglyceride (TAG levels. A parallel decrease in some of the taxa associated with the production of trimethylamine, suggest an increase in choline absorption and bioavailability with transformation to betaine. The latter may partially explain the previously observed effect of nopal on the development of hepatic steatosis. In conclusion, this study provides new evidence on the effects of nopal consumption on normal and HF-diet induced changes in the intestine, the liver and systemic metabolism.

  4. Extracellular vesicles regulate immune responses and cellular function in intestinal inflammation and repair.

    Science.gov (United States)

    Bui, Triet M; Mascarenhas, Lorraine A; Sumagin, Ronen

    2018-02-02

    Tightly controlled communication among the various resident and recruited cells in the intestinal tissue is critical for maintaining tissue homeostasis, re-establishment of the barrier function and healing responses following injury. Emerging evidence convincingly implicates extracellular vesicles (EVs) in facilitating this important cell-to-cell crosstalk by transporting bioactive effectors and genetic information in healthy tissue and disease. While many aspects of EV biology, including release mechanisms, cargo packaging, and uptake by target cells are still not completely understood, EVs contribution to cellular signaling and function is apparent. Moreover, EV research has already sparked a clinical interest, as a potential diagnostic, prognostic and therapeutic tool. The current review will discuss the function of EVs originating from innate immune cells, namely, neutrophils, monocytes and macrophages, as well as intestinal epithelial cells in healthy tissue and inflammatory disorders of the intestinal tract. Our discussion will specifically emphasize the contribution of EVs to the regulation of vascular and epithelial barrier function in inflamed intestines, wound healing, as well as trafficking and activity of resident and recruited immune cells.

  5. Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer.

    Science.gov (United States)

    Fasano, Alessio

    2011-01-01

    The primary functions of the gastrointestinal tract have traditionally been perceived to be limited to the digestion and absorption of nutrients and to electrolytes and water homeostasis. A more attentive analysis of the anatomic and functional arrangement of the gastrointestinal tract, however, suggests that another extremely important function of this organ is its ability to regulate the trafficking of macromolecules between the environment and the host through a barrier mechanism. Together with the gut-associated lymphoid tissue and the neuroendocrine network, the intestinal epithelial barrier, with its intercellular tight junctions, controls the equilibrium between tolerance and immunity to non-self antigens. Zonulin is the only physiological modulator of intercellular tight junctions described so far that is involved in trafficking of macromolecules and, therefore, in tolerance/immune response balance. When the finely tuned zonulin pathway is deregulated in genetically susceptible individuals, both intestinal and extraintestinal autoimmune, inflammatory, and neoplastic disorders can occur. This new paradigm subverts traditional theories underlying the development of these diseases and suggests that these processes can be arrested if the interplay between genes and environmental triggers is prevented by reestablishing the zonulin-dependent intestinal barrier function. This review is timely given the increased interest in the role of a "leaky gut" in the pathogenesis of several pathological conditions targeting both the intestine and extraintestinal organs.

  6. Fecal Markers of Intestinal Inflammation and Permeability Associated with the Subsequent Acquisition of Linear Growth Deficits in Infants

    Science.gov (United States)

    Kosek, Margaret; Haque, Rashidul; Lima, Aldo; Babji, Sudhir; Shrestha, Sanjaya; Qureshi, Shahida; Amidou, Samie; Mduma, Estomih; Lee, Gwenyth; Yori, Pablo Peñataro; Guerrant, Richard L.; Bhutta, Zulfiqar; Mason, Carl; Kang, Gagandeep; Kabir, Mamun; Amour, Caroline; Bessong, Pascal; Turab, Ali; Seidman, Jessica; Olortegui, Maribel Paredes; Quetz, Josiane; Lang, Dennis; Gratz, Jean; Miller, Mark; Gottlieb, Michael

    2013-01-01

    Enteric infections are associated with linear growth failure in children. To quantify the association between intestinal inflammation and linear growth failure three commercially available enzyme-linked immunosorbent assays (neopterin [NEO], alpha-anti-trypsin [AAT], and myeloperoxidase [MPO]) were performed in a structured sampling of asymptomatic stool from children under longitudinal surveillance for diarrheal illness in eight countries. Samples from 537 children contributed 1,169 AAT, 916 MPO, and 954 NEO test results that were significantly associated with linear growth. When combined to form a disease activity score, children with the highest score grew 1.08 cm less than children with the lowest score over the 6-month period following the tests after controlling for the incidence of diarrheal disease. This set of affordable non-invasive tests delineates those at risk of linear growth failure and may be used for the improved assessments of interventions to optimize growth during a critical period of early childhood. PMID:23185075

  7. Treatment with bone marrow mesenchymal stem cells combined with plumbagin alleviates spinal cord injury by affecting oxidative stress, inflammation, apoptotis and the activation of the Nrf2 pathway.

    Science.gov (United States)

    Yang, Wencheng; Yang, Yan; Yang, Jian-Yi; Liang, Ming; Song, Jiangtao

    2016-04-01

    The aim of the present study was to investigate the protective effect exerted by bone marrow mesenchymal stem cells (BMSCs) in combination with plumbagin on spinal cord injury (SCI) and explore the mechanism behind this protective effect. Firstly, BMSCs were extracted from male Sprague-Dawley rats, cultured in vitro, and identified by hematoxylin. Sprague-Dawley rats were then randomly divided into a control group, SCI model group, BMSC-treated group, a plumbagin-treated group, and a BMSC and plumbagin-treated group. After treatment with BMSCs combined with plumbagin, a Basso, Beattie and Bresnahan (BBB) test was carried out and the spinal cord water content was examined in order to analyze the effect of BMSCs combined with plumbagin on SCI. The myeloperoxidase (MPO), superoxide dismutase (SOD), malondialdehyde (MDA), nuclear factor-κB (NF-κB) p65 unit, tumor necrosis factor-α (TNF-α) levels were also detected. Moreover, nuclear factor erythroid 2‑related factor 2 (Nrf2), phosphoinositide 3-kinase (PI3K), phosphorylated (p-)Akt, p-p38 mitogen-activated protein kinase (MAPK), and p-extracellular-signal-regulated kinase (ERK) protein expression levels were measured using western blot analysis. Treatment with BMSCs combined with plumbagin significantly improved locomotor recovery and reduced the spinal cord water content after SCI. The increased MPO, MDA, NF-κB p65 and TNF-α levels were significantly suppressed and the decreased SOD was significantly increased in SCI rats. The suppression of Nrf2, p-Akt and p-ERK, as well as the promotion of p-p38 MAPK, were reversed by treatment with BMSCs combined with plumbagin. These effects suggest that treatment with BMSCs combined with plumbagin alleviates SCI through its effects on oxidative stress, inflammation, apoptotis and activation of the Nrf2 pathway.

  8. Decreased leukocyte recruitment by inorganic nitrate and nitrite in microvascular inflammation and NSAID-induced intestinal injury.

    Science.gov (United States)

    Jädert, Cecilia; Petersson, Joel; Massena, Sara; Ahl, David; Grapensparr, Liza; Holm, Lena; Lundberg, Jon O; Phillipson, Mia

    2012-02-01

    Nitric oxide (NO) generated by vascular NO synthases can exert anti-inflammatory effects, partly through its ability to decrease leukocyte recruitment. Inorganic nitrate and nitrite, from endogenous or dietary sources, have emerged as alternative substrates for NO formation in mammals. Bioactivation of nitrate is believed to require initial reduction to nitrite by oral commensal bacteria. Here we investigated the effects of inorganic nitrate and nitrite on leukocyte recruitment in microvascular inflammation and in NSAID-induced small-intestinal injury. We show that leukocyte emigration in response to the proinflammatory chemokine MIP-2 is reduced by 70% after 7 days of dietary nitrate supplementation as well as by acute intravenous nitrite administration. Nitrite also reduced leukocyte adhesion to a similar extent and this effect was inhibited by the soluble guanylyl cyclase inhibitor ODQ, whereas the effect on emigrated leukocytes was not altered by this treatment. Further studies in TNF-α-stimulated endothelial cells revealed that nitrite dose-dependently reduced the expression of ICAM-1. In rats and mice subjected to a challenge with diclofenac, dietary nitrate prevented the increase in myeloperoxidase and P-selectin levels in small-intestinal tissue. Antiseptic mouthwash, which eliminates oral nitrate reduction, markedly blunted the protective effect of dietary nitrate on P-selectin levels. Despite attenuation of the acute immune response, the overall ability to clear an infection with Staphylococcus aureus was not suppressed by dietary nitrate as revealed by noninvasive IVIS imaging. We conclude that dietary nitrate markedly reduces leukocyte recruitment to inflammation in a process involving attenuation of P-selectin and ICAM-1 upregulation. Bioactivation of dietary nitrate requires intermediate formation of nitrite by oral nitrate-reducing bacteria and then probably further reduction to NO and other bioactive nitrogen oxides in the tissues. Copyright

  9. Extraintestinal pathogenic Escherichia coli are associated with intestinal inflammation in patients with ulcerative colitis

    DEFF Research Database (Denmark)

    Mirsepasi-Lauridsen, Hengameh C.; Halkjaer, Sofie Ingdam; Mortensen, Esben Munk

    2016-01-01

    E. coli of the phylogenetic group B2 harbouring Extra intestinal Pathogenic Escherichia coli (ExPEC) genes are frequently seen as colonizers of the intestine in patients with active ulcerative colitis (UC). In this study, we describe the influence of E. coli Nissle (EcN) B2 as add-on treatment....... We showed that in the active UC patient group receiving Placebo/EcN, fewer patients reached remission, in comparison to the patient group receiving Placebo/placebo (p UC patients initially colonized with E. coli B2 had increased fecal calprotectin values and Colitis Activity Index...... to conventional therapies in patients with active UC. For this study one hundred active UC patients were randomized to ciprofloxacin or placebo for 1 week followed by EcN or placebo for 7 weeks. Stool samples were collected at weeks 0, 1, 8, 12, where E. coli were characterized and fecal calprotectin was measured...

  10. Anti-inflammatory mechanism of metformin and its effects in intestinal inflammation and colitis-associated colon cancer.

    Science.gov (United States)

    Koh, Seong-Joon; Kim, Jung Mogg; Kim, In-Kyoung; Ko, Su Hyuk; Kim, Joo Sung

    2014-03-01

    The aim of this study is to evaluate the effect of metformin on intestinal inflammation. COLO205 cells were pretreated with metformin and stimulated with tumor necrosis factor (TNF)-α. Expression of interleukin (IL)-8 was determined by luciferase assay and real-time PCR. Inhibitor of kappaB (IκB) phosphorylation/degradation and adenosine monohosphate-activated protein kinase (AMPK) activity were evaluated by Western blotting. DNA-binding activity of transcription factor nuclear factor-kappaB (NF-κB) was assessed by electrophoretic mobility shift assay. In an acute colitis model, mice were given 4% dextran sulfate sodium (DSS) for 5 days. IL-10−/− mice were used to evaluate the effect of metformin on chronic colitis. In an inflamation-associated tumor model, mice were given a single intraperitoneal injection of azoxymethane followed by three cycles of 2% DSS for 5 days and 2 weeks of free water consumption. Metformin significantly inhibited IL-8 induction in COLO 205 cells stimulated with TNF-α. Metformin attenuated IκBα phosphorylation and NF-κB DNA-binding activity. Administration of metformin significantly reduced the severity of DSS-induced colitis. In addition, DSS-induced IκB kinase (IKK) activation was significantly reduced in mice treated with metformin. Metformin significantly attenuated the severity of colitis in IL-10−/− mice, induced AMPK activity in intestinal epithelial cells, and inhibited the development of colitic cancer in mice. These results indicate that metformin suppresses NF-κB activation in intestinal epithelial cells and ameliorates murine colitis and colitis-associated tumorigenesis in mice, suggesting that metformin could be a potential therapeutic agent for the treatment of inflammatory bowel disease.

  11. Zeyheria montana Mart. (Bignoniaceae) as source of antioxidant and immunomodulatory compounds with beneficial effects on intestinal inflammation.

    Science.gov (United States)

    Seito, Leonardo Noboru; Sforcin, José Maurício; Bastos, Jairo Kenupp; Di Stasi, Luiz Claudio

    2015-04-01

    Zeyheria montana is a medicinal plant used in Brazilian folk medicine for treating skin affections, ulcers, inflammation and diarrhoea, and as an antisyphilitic and antiblenorrhagic agent, but little is known about its mechanisms of action. Herein, a bio-guided assay was carried out to further evaluate its antioxidant and immunomodulatory effects, and the possible benefits on experimental intestinal inflammation. Extracts, partitions, fractions and isolated compounds were tested for inhibition of lipid peroxidation. Isolated compounds were tested in vitro for its antioxidant and immunomodulatory action prior to in-vivo evaluation in trinitrobenzenesulfonic acid-induced rat colitis. Two major compounds were identified in the leaf dichloromethane extract: 3'-hydroxy-5,7,4'-trimethoxyflavone and 6-hydroxy-5,7-dimethoxyflavone, which exhibited an antioxidant activity. The compounds protected the colonic glutathione levels in more than 90% despite the absence of protection against the gross macroscopic colonic damage. In addition, the compounds inhibited IL-1ß secretion by macrophages in 91.5% and 72.7% respectively, whereas both reduced IL-6 secretion in about 44.5%. The major active compounds from Z. montana leaves exerted antioxidant and immunomodulatory effects, endorsing the use of Z. montana in folk medicine as an anti-inflammatory agent. However, further investigation is still needed regarding medicinal plants and the identification of candidate compounds for the treatment of the inflammatory bowel diseases. © 2014 Royal Pharmaceutical Society.

  12. Intestinal inflammation modulates expression of 11beta-hydroxysteroid dehydrogenase in murine gut

    Czech Academy of Sciences Publication Activity Database

    Vagnerová, Karla; Kverka, Miloslav; Klusoňová, Petra; Ergang, Peter; Mikšík, Ivan; Tlaskalová, Helena; Pácha, Jiří

    2006-01-01

    Roč. 191, č. 2 (2006), s. 497-503 ISSN 0022-0795 R&D Projects: GA MZd(CZ) NR8576; GA AV ČR(CZ) KJB5011402; GA AV ČR(CZ) IAA5020205; GA AV ČR(CZ) 1QS500200572 Institutional research plan: CEZ:AV0Z50110509; CEZ:AV0Z50200510 Keywords : inflammation * glucocorticoid metabolism Subject RIV: ED - Physiology Impact factor: 3.072, year: 2006

  13. Intestinal Microbiota Promotes Psoriasis-Like Skin Inflammation by Enhancing Th17 Response.

    Directory of Open Access Journals (Sweden)

    Zuzana Zákostelská

    Full Text Available Psoriasis is a chronic inflammatory skin disease in which Th17 cells play a crucial role. Since indigenous gut microbiota influences the development and reactivity of immune cells, we analyzed the link among microbiota, T cells and the formation of psoriatic lesions in the imiquimod-induced murine model of psoriasis. To explore the role of microbiota, we induced skin inflammation in germ-free (GF, broad-spectrum antibiotic (ATB-treated or conventional (CV BALB/c and C57BL/6 mice. We found that both mice reared in GF conditions for several generations and CV mice treated with ATB were more resistant to imiquimod-induced skin inflammation than CV mice. The ATB treatment dramatically changed the diversity of gut bacteria, which remained stable after subsequent imiquimod application; ATB treatment resulted in a substantial increase in the order Lactobacillales and a significant decrease in Coriobacteriales and Clostridiales. Moreover, as compared to CV mice, imiquimod induced a lower degree of local and systemic Th17 activation in both GF and ATB-treated mice. These findings suggest that gut microbiota control imiquimod-induced skin inflammation by altering the T cell response.

  14. VSL#3 probiotic upregulates intestinal mucosal alkaline sphingomyelinase and reduces inflammation

    Science.gov (United States)

    Soo, Isaac; Madsen, Karen L; Tejpar, Qassim; Sydora, Beate C; Sherbaniuk, Richard; Cinque, Benedetta; Di Marzio, Luisa; Cifone, Maria Grazia; Desimone, Claudio; Fedorak, Richard N

    2008-01-01

    BACKGROUND: Alkaline sphingomyelinase, an enzyme found exclusively in bile and the intestinal brush border, hydrolyzes sphingomyelin into ceramide, sphingosine and sphingosine-1-phosphate, thereby inducing epithelial apoptosis. Reduced levels of alkaline sphingomyelinase have been found in premalignant and malignant intestinal epithelia and in ulcerative colitis tissue. Probiotic bacteria can be a source of sphingomyelinase. OBJECTIVE: To determine the effect of VSL#3 probiotic therapy on mucosal levels of alkaline sphingomyelinase, both in a mouse model of colitis and in patients with ulcerative colitis. METHODS: Interleukin-10 gene-deficient (IL10KO) and wild type control mice were treated with VSL#3 (109 colony-forming units per day) for three weeks, after which alkaline sphingomyelinase activity was measured in ileal and colonic tissue. As well, 15 patients with ulcerative colitis were treated with VSL#3 (900 billion bacteria two times per day for five weeks). Alkaline sphingomyelinase activity was measured through biopsies and comparison of ulcerative colitis disease activity index scores obtained before and after treatment. RESULTS: Lowered alkaline sphingomyelinase levels were seen in the colon (P=0.02) and ileum (P=0.04) of IL10KO mice, as compared with controls. Treatment of these mice with VSL#3 resulted in upregulation of mucosal alkaline sphingomyelinase activity in both the colon (P=0.04) and the ileum (P=0.01). VSL#3 treatment of human patients who had ulcerative colitis decreased mean (± SEM) ulcerative colitis disease activity index scores from 5.3±1.8946 to 0.70±0.34 (P=0.02) and increased mucosal alkaline sphingomyelinase activity. CONCLUSION: Mucosal alkaline sphingomyelinase activity is reduced in the intestine of IL10KO mice with colitis and in humans with ulcerative colitis. VSL#3 probiotic therapy upregulates mucosal alkaline sphingomyelinase activity. PMID:18354751

  15. 4-methylesculetin, a coumarin derivative, ameliorates dextran sulfate sodium-induced intestinal inflammation.

    Science.gov (United States)

    Witaicenis, Aline; de Oliveira, Ellen Cristina Souza; Tanimoto, Alexandre; Zorzella-Pezavento, Sofia Fernanda Gonçalves; de Oliveira, Silvio Luis; Sartori, Alexandrina; Di Stasi, Luiz Claudio

    2018-01-25

    4-methylesculetin is one of the coumarin derivatives with great anti-oxidant and anti-inflammatory activities. Recent studies have shown that 4-methylesculetin has a promising potentiality to treat inflammatory diseases, especially those related to reactive oxygen species, as inflammatory bowel disease. Based on this, the present study aims to investigate the intestinal anti-inflammatory activity of 4-methylesculetin in dextran sulfate sodium (DSS) model. For this purpose, mice received DSS 5% for 5 days followed by 2 days of filtered tap water. Treated groups received orally 5 or 25 mg/kg of 4-methylesculetin daily since the first day. Macroscopic, microscopic and biochemical parameters were evaluated. 4-methylesculetin (25 mg/kg) improved microscopic parameters, decreased MPO activity, reduced the colonic levels of IL-6 and counteracted GSH depletion when compared with DSS-control group. Our results show the intestinal anti-inflammatory activity of 4-methylesculetin in DSS model, which is related to its antioxidant and anti-inflammatory properties. This way, 4-methylesculetin, is a new potential compound for treatment of both types of IBD. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. The role of rose hip (Rosa canina L powder in alleviating arthritis pain and inflammation – part II animal and human studies

    Directory of Open Access Journals (Sweden)

    Marstr

    2016-05-01

    Full Text Available Kristian Marstrand,1 Joan Campbell-Tofte2 1Department of Orthopaedic Surgery, Elverum Hospital, Elverum, Norway; 2Coordinating Research Unit, Frederiksberg University Hospital, Frederiksberg, Copenhagen, Denmark Abstract: Rosa canina fruits (often known as rose hip have been used in herbal remedies since ancient times. On the basis of anecdotal reports about the effects of rose hip preparations on human health and citations to the same in ancient texts, in vitro and in vivo studies have been conducted that have made it possible to learn about some active ingredients in rose hip, as well as how the component compounds might exert their effects. From such studies, it has been documented that there is a great variation in active ingredients when comparing different rose hip products. Factors which affect the quality and quantity of active ingredients in the rose hip products include the subspecies of the particular R. canina from which the fruits are harvested, the environment during plant growth, time of harvesting, and the amount of seeds and shells/husks incorporated into the preparation. Studies in animals and in humans are of great importance for determining the true bio-effects of rose hip. Such in vivo studies that have only been performed during the last 2 decades indicate that the treatment of patients with different types of joint disease with rose hip powder based on a subspecies of R. canina (Lito containing a certain galactolipid (GOPO can alleviate pain, improve daily activity, and even reduce the consumption of regular pain relievers. As several rose hip components have been shown to be anti-inflammatory, it is suggested that anti-inflammatory mechanisms might explain some reductions in symptoms associated with administering rose hip to arthritic conditions. Although the number of publications of randomized and placebo-controlled clinic studies with rose hip is small, the overriding evidence is that the anti-inflammatory effects from

  17. Can Monitoring Fetal Intestinal Inflammation Using Heart Rate Variability Analysis Signal Incipient Necrotizing Enterocolitis of the Neonate?

    Science.gov (United States)

    Liu, Hai Lun; Garzoni, Luca; Herry, Christophe; Durosier, Lucien Daniel; Cao, Mingju; Burns, Patrick; Fecteau, Gilles; Desrochers, André; Patey, Natalie; Seely, Andrew J E; Faure, Christophe; Frasch, Martin G

    2016-04-01

    Necrotizing enterocolitis of the neonate is an acute inflammatory intestinal disease that can cause necrosis and sepsis. Chorioamnionitis is a risk factor of necrotizing enterocolitis. The gut represents the biggest vagus-innervated organ. Vagal activity can be measured via fetal heart rate variability. We hypothesized that fetal heart rate variability can detect fetuses with incipient gut inflammation. Prospective animal study. University research laboratory. Chronically instrumented near-term fetal sheep (n = 21). Animals were surgically instrumented with vascular catheters and electrocardiogram to allow manipulation and recording from nonanesthetized animals. In 14 fetal sheep, inflammation was induced with lipopolysaccharide (IV) to mimic chorioamnionitis. Fetal arterial blood samples were drawn at selected time points over 54 hours post lipopolysaccharide for blood gas and cytokines (interleukin-6 and tumor necrosis factor-α enzymelinked immunosorbent assay). Fetal heart rateV was quantified throughout the experiment. The time-matched fetal heart rate variability measures were correlated to the levels of interleukin-6 and tumor necrosis factor-α. Upon necropsy, ionized calcium binding adaptor molecule 1+ (Iba1+), CD11c+ (M1), CD206+ (M2 macrophages), and occludin (leakiness marker) immunofluorescence in the terminal ileum was quantified along with regional Iba1+ signal in the brain (microglia). Interleukin-6 peaked at 3 hours post lipopolysaccharide accompanied by mild cardiovascular signs of sepsis. At 54 hours, we identified an increase in Iba1+ and, specifically, M1 macrophages in the ileum accompanied by increased leakiness, with no change in Iba1 signal in the brain. Preceding this change on tissue level, at 24 hours, a subset of nine fetal heart rate variability measures correlated exclusively to the Iba+ markers of ileal, but not brain, inflammation. An additional fetal heart rate variability measure, mean of the differences of R-R intervals

  18. Infliximab's influence on anastomotic strength and degree of inflammation in intestinal surgery in a rabbit model

    DEFF Research Database (Denmark)

    Frostberg, Erik; Ström, Petter; Gerke, Oke

    2014-01-01

    BACKGROUND: Infliximab, a TNF-alpha inhibitor, is a potent anti-inflammatory drug in the treatment of inflammatory bowel diseases. Recent studies have investigated the effect of infliximab treatment on postoperative complications such as anastomotic leakage, however, with conflicting results...... and conclusions. The purpose of this study was to investigate whether a single dose infliximab has an adverse effect on the anastomotic healing process, observed as reduced anastomotic breaking strength and histopathologically verified lower grade of inflammatory response, in the small intestine of a rabbit....... METHODS: Thirty New Zealand rabbits (median weight 2.5 kg) were allocated to treatment with an intravenous bolus of either 10 mg/kg infliximab (n = 15) or placebo (n = 15). One week later all rabbits underwent two separate end-to-end anastomoses in the jejunum under general anesthesia. At postoperative...

  19. Investigation of Microbiota Alterations and Intestinal Inflammation Post-Spinal Cord Injury in Rat Model.

    Science.gov (United States)

    O'Connor, Gregory; Jeffrey, Elisabeth; Madorma, Derik; Marcillo, Alexander; Abreu, Maria T; Deo, Sapna K; Dietrich, W Dalton; Daunert, Sylvia

    2018-03-23

    Although there has been a significant amount of research focused on the pathophysiology of Spinal Cord Injury (SCI), there is limited information on the consequences of SCI on remote organs. SCI can produce significant effects on a variety of organ systems, including the gastrointestinal tract. Patients with SCI often suffer from severe, debilitating bowel dysfunction in addition to their physical disabilities, which is of major concern for these individuals due to the adverse impact on their quality of life. Herein, we report on our investigation into the effects of SCI and subsequent antibiotic treatment on the intestinal tissue and microbiota. For that, we employed a thoracic SCI rat model and investigated changes to the microbiota, pro-inflammatory cytokine levels, and bacterial communication molecule levels post injury and gentamicin treatment for seven days. We discovered significant changes, the most interesting being the differences in the gut microbiota beta diversity of 8-week SCI animals compared to control animals at the family, genus, and species level. Specifically, 35 Operational Taxonomic Units (OTUs) were enriched in the SCI animal group and 3 were identified at species level; Lactobacillus intestinalis, Clostridium disporicum, and Bifidobacterium choerinum. In contrast, Clostridium saccharogumia was identified as depleted in the SCI animal group. Pro-inflammatory cytokines IL-12, MIP-2, and TNF-α, were found to be significantly elevated in intestinal tissue homogenate 4-weeks post-SCI compared to 8-weeks post-injury. Further, levels of IL-1β, IL-12, and MIP-2 significantly correlated with changes in beta diversity 8-weeks post-SCI. Our data provide a greater understanding of the early effects of SCI on the microbiota and gastrointestinal tract, highlighting the need for further investigation to elucidate the mechanism underlying these effects.

  20. Transient inhibition of ROR-γt therapeutically limits intestinal inflammation by reducing TH17 cells and preserving group 3 innate lymphoid cells.

    Science.gov (United States)

    Withers, David R; Hepworth, Matthew R; Wang, Xinxin; Mackley, Emma C; Halford, Emily E; Dutton, Emma E; Marriott, Clare L; Brucklacher-Waldert, Verena; Veldhoen, Marc; Kelsen, Judith; Baldassano, Robert N; Sonnenberg, Gregory F

    2016-03-01

    RAR-related orphan receptor-γt (ROR-γt) directs differentiation of proinflammatory T helper 17 (TH17) cells and is a potential therapeutic target in chronic autoimmune and inflammatory diseases. However, ROR-γt-dependent group 3 innate lymphoid cells ILC3s provide essential immunity and tissue protection in the intestine, suggesting that targeting ROR-γt could also result in impaired host defense after infection or enhanced tissue damage. Here, we demonstrate that transient chemical inhibition of ROR-γt in mice selectively reduces cytokine production from TH17 but not ILCs in the context of intestinal infection with Citrobacter rodentium, resulting in preserved innate immunity. Temporal deletion of Rorc (encoding ROR-γt) in mature ILCs also did not impair cytokine response in the steady state or during infection. Finally, pharmacologic inhibition of ROR-γt provided therapeutic benefit in mouse models of intestinal inflammation and reduced the frequency of TH17 cells but not ILCs isolated from primary intestinal samples of individuals with inflammatory bowel disease (IBD). Collectively, these results reveal differential requirements for ROR-γt in the maintenance of TH17 cell and ILC3 responses and suggest that transient inhibition of ROR-γt is a safe and effective therapeutic approach during intestinal inflammation.

  1. Toxoplasma gondii Oral Infection Induces Intestinal Inflammation and Retinochoroiditis in Mice Genetically Selected for Immune Oral Tolerance Resistance

    Science.gov (United States)

    Dias, Raul Ramos Furtado; de Carvalho, Eulógio Carlos Queiroz; Leite, Carla Cristina da Silva; Tedesco, Roberto Carlos; Calabrese, Katia da Silva; Silva, Antonio Carlos; DaMatta, Renato Augusto; de Fatima Sarro-Silva, Maria

    2014-01-01

    Toxoplasmosis is a worldwide disease with most of the infections originating through the oral route and generates various pathological manifestations, ranging from meningoencephalitis to retinochoroiditis and inflammatory bowel disease. Animal models for these pathologies are scarce and have limitations. We evaluated the outcome of Toxoplasma gondii oral infection with 50 or 100 cysts of the ME-49 strain in two lines of mice with extreme phenotypes of susceptibility (TS) or resistance (TR) to immune oral tolerance. Therefore, the aim of this study was to evaluate the behaviour of TS and TR mice, orally infected by T. gondii, and determine its value as a model for inflammatory diseases study. Mortality during the acute stage of the infection for TR was 50% for both dosages, while 10 and 40% of the TS died after infection with these respective dosages. In the chronic stage, the remaining TS succumbed while TR survived for 90 days. The TS displayed higher parasite load with lower intestinal inflammation and cellular proliferation, notwithstanding myocarditis, pneumonitis and meningoencephalitis. TR presented massive necrosis of villi and crypt, comparable to inflammatory bowel disease, with infiltration of lymphoid cells in the lamina propria of the intestines. Also, TR mice infected with 100 cysts presented intense cellular infiltrate within the photoreceptor layer of the eyes, changes in disposition and morphology of the retina cell layers and retinochoroiditis. During the infection, high levels of IL-6 were detected in the serum of TS mice and TR mice presented high amounts of IFN-γ and TNF-α. Both mice lineages developed different disease outcomes, but it is emphasized that TR and TS mice presented acute and chronic stages of the infection, demonstrating that the two lineages offer an attractive model for studying toxoplasmosis. PMID:25437299

  2. Toxoplasma gondii oral infection induces intestinal inflammation and retinochoroiditis in mice genetically selected for immune oral tolerance resistance.

    Directory of Open Access Journals (Sweden)

    Raul Ramos Furtado Dias

    Full Text Available Toxoplasmosis is a worldwide disease with most of the infections originating through the oral route and generates various pathological manifestations, ranging from meningoencephalitis to retinochoroiditis and inflammatory bowel disease. Animal models for these pathologies are scarce and have limitations. We evaluated the outcome of Toxoplasma gondii oral infection with 50 or 100 cysts of the ME-49 strain in two lines of mice with extreme phenotypes of susceptibility (TS or resistance (TR to immune oral tolerance. Therefore, the aim of this study was to evaluate the behaviour of TS and TR mice, orally infected by T. gondii, and determine its value as a model for inflammatory diseases study. Mortality during the acute stage of the infection for TR was 50% for both dosages, while 10 and 40% of the TS died after infection with these respective dosages. In the chronic stage, the remaining TS succumbed while TR survived for 90 days. The TS displayed higher parasite load with lower intestinal inflammation and cellular proliferation, notwithstanding myocarditis, pneumonitis and meningoencephalitis. TR presented massive necrosis of villi and crypt, comparable to inflammatory bowel disease, with infiltration of lymphoid cells in the lamina propria of the intestines. Also, TR mice infected with 100 cysts presented intense cellular infiltrate within the photoreceptor layer of the eyes, changes in disposition and morphology of the retina cell layers and retinochoroiditis. During the infection, high levels of IL-6 were detected in the serum of TS mice and TR mice presented high amounts of IFN-γ and TNF-α. Both mice lineages developed different disease outcomes, but it is emphasized that TR and TS mice presented acute and chronic stages of the infection, demonstrating that the two lineages offer an attractive model for studying toxoplasmosis.

  3. TLR2/TLR4 activation induces Tregs and suppresses intestinal inflammation caused by Fusobacterium nucleatum in vivo.

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    Yin-Ping Jia

    Full Text Available Toll-like receptors (TLRs 2 and 4 play critical roles in intestinal inflammation caused by Fusobacterium nucleatum (F. nucleatum infection, but the role of TLR2/TLR4 in regulation of proinflammatory cytokines remains unknown. In this study, through microarray analysis and qRT-PCR, we showed that TLR2/TLR4 are involved in the F. nucleatum-induced inflammatory signaling pathway in Caco-2 cells, C57BL/6 mice and human clinical specimens. In TLR2-/- and TLR4-/- mice, F. nucleatum infection resulted in increased colonization of the bacteria and production of the proinflammatory cytokines IL-8, IL-1β and TNF-α. In addition, the ratio of Foxp3+ CD4+ T cells in the total CD4+ T cells in TLR2-/- and TLR4-/- mice was less than that in wild-type mice, and the ratio in hybrid mice was more than that in knockout mice, which suggested that TLR2/TLR4 mediated the number of Tregs. Furthermore, it was observed that inflammatory cytokine levels were reduced in TLR2-/- mice after Treg transfer. Thus, these data indicate that TLR2/TLR4 regulate F. nucleatum-induced inflammatory cytokines through Tregs in vivo.

  4. L-carnitine, a diet component and organic cation transporter OCTN ligand, displays immunosuppressive properties and abrogates intestinal inflammation.

    Science.gov (United States)

    Fortin, G; Yurchenko, K; Collette, C; Rubio, M; Villani, A-C; Bitton, A; Sarfati, M; Franchimont, D

    2009-04-01

    Allele variants in the L-carnitine (LCAR) transporters OCTN1 (SLC22A4, 1672 C --> T) and OCTN2 (SLC22A5, -207 G --> C) have been implicated in susceptibility to Crohn's disease (CD). LCAR is consumed in the diet and transported actively from the intestinal lumen via the organic cation transporter OCTN2. While recognized mainly for its role in fatty acid metabolism, several lines of evidence suggest that LCAR may also display immunosuppressive properties. This study sought to investigate the immunomodulatory capacity of LCAR on antigen-presenting cell (APC) and CD4+ T cell function by examining cytokine production and the expression of activation markers in LCAR-supplemented and deficient cell culture systems. The therapeutic efficacy of its systemic administration was then evaluated during the establishment of colonic inflammation in vivo. LCAR treatment significantly inhibited both APC and CD4+ T cell function, as assessed by the expression of classical activation markers, proliferation and cytokine production. Carnitine deficiency resulted in the hyperactivation of CD4+ T cells and enhanced cytokine production. In vivo, protection from trinitrobenzene sulphonic acid colitis was observed in LCAR-treated mice and was attributed to the abrogation of both innate [interleukin (IL)-1beta and IL-6 production] and adaptive (T cell proliferation in draining lymph nodes) immune responses. LCAR therapy may therefore represent a novel alternative therapeutic strategy and highlights the role of diet in CD.

  5. TLR2/TLR4 activation induces Tregs and suppresses intestinal inflammation caused by Fusobacterium nucleatum in vivo.

    Science.gov (United States)

    Jia, Yin-Ping; Wang, Kun; Zhang, Zhu-Jun; Tong, Ya-Nan; Han, Dan; Hu, Chun-Yu; Li, Qian; Xiang, Yang; Mao, Xu-Hu; Tang, Bin

    2017-01-01

    Toll-like receptors (TLRs) 2 and 4 play critical roles in intestinal inflammation caused by Fusobacterium nucleatum (F. nucleatum) infection, but the role of TLR2/TLR4 in regulation of proinflammatory cytokines remains unknown. In this study, through microarray analysis and qRT-PCR, we showed that TLR2/TLR4 are involved in the F. nucleatum-induced inflammatory signaling pathway in Caco-2 cells, C57BL/6 mice and human clinical specimens. In TLR2-/- and TLR4-/- mice, F. nucleatum infection resulted in increased colonization of the bacteria and production of the proinflammatory cytokines IL-8, IL-1β and TNF-α. In addition, the ratio of Foxp3+ CD4+ T cells in the total CD4+ T cells in TLR2-/- and TLR4-/- mice was less than that in wild-type mice, and the ratio in hybrid mice was more than that in knockout mice, which suggested that TLR2/TLR4 mediated the number of Tregs. Furthermore, it was observed that inflammatory cytokine levels were reduced in TLR2-/- mice after Treg transfer. Thus, these data indicate that TLR2/TLR4 regulate F. nucleatum-induced inflammatory cytokines through Tregs in vivo.

  6. Inflammation neither increases hepatic hepcidin nor affects intestinal (59)Fe-absorption in two murine models of bowel inflammation, hemizygous TNF(ΔARE/+) and homozygous IL-10(-/-) mice.

    Science.gov (United States)

    Buffler, M; Becker, C; Windisch, W; Schümann, K

    2015-10-01

    Hepcidin-synthesis was reported to be stimulated by inflammation. In contrast, hepcidin synthesis was inhibited by TNFα and serum hepcidin was low. To elucidate these contradictions, we compare data on hepcidin expression, on iron absorption and homoeostasis and markers of inflammation between two murine models of intestinal inflammation and corresponding wild-types as determined by standard methods. In TNF(ΔARE/+) and IL-10(-/-)-mice hepatic hepcidin expression and protein content was significantly lower than in corresponding wild-types. However, (59)Fe whole-body retention showed no difference between knock-outs and corresponding wild-types 7d after gavage, in neither strain. Compared to wild-types, body weight, hepatic non-haem iron content, hemoglobin and hematocrit were significantly decreased in TNF(ΔARE/+) mice, while erythropoiesis increased. These differences were not seen in IL-10(-/-) mice. Duodenal IL-6 and TNFα content increased significantly in TNF(ΔARE/+) mice, while ferritin-H decreased along with hepatic hepcidin expression, ferritin L, and non-haem iron. In IL-10(-/-) mice, these changes were less marked or missing for non-haem iron. Duodenal ferritin-L and ferroportin increased significantly, while HFE decreased. Our results corroborate the conflicting combination of low hepcidin with inflammation and without increased intestinal iron absorption. Speculating on underlying mechanism, decreased hepcidin may result from stimulated erythropoiesis. Unaltered intestinal iron-absorption may compromise between the stimulation by increased erythropoiesis and inhibition by local and systemic inflammation. The findings suggest intense interaction between counterproductive mechanisms and ask for further research. Copyright © 2015 Elsevier GmbH. All rights reserved.

  7. T-lymphocyte responses to intestinally absorbed antigens can contribute to adipose tissue inflammation and glucose intolerance during high fat feeding.

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    Yuehui Wang

    Full Text Available BACKGROUND: Obesity is associated with inflammation of visceral adipose tissues, which increases the risk for insulin resistance. Animal models suggest that T-lymphocyte infiltration is an important early step, although it is unclear why these cells are attracted. We have recently demonstrated that dietary triglycerides, major components of high fat diets, promote intestinal absorption of a protein antigen (ovalbumin, "OVA". The antigen was partly transported on chylomicrons, which are prominently cleared in adipose tissues. We hypothesized that intestinally absorbed gut antigens may cause T-lymphocyte associated inflammation in adipose tissue. METHODOLOGY/PRINCIPAL FINDINGS: Triglyceride absorption promoted intestinal absorption of OVA into adipose tissue, in a chylomicron-dependent manner. Absorption tended to be higher in mesenteric than subcutaneous adipose tissue, and was lowest in gonadal tissue. OVA immunoreactivity was detected in stromal vascular cells, including endothelial cells. In OVA-sensitized mice, OVA feeding caused marked accumulation of CD3+ and osteopontin+ cells in mesenteric adipose tissue. The accumulating T-lymphocytes were mainly CD4+. As expected, high-fat (60% kCal diets promoted mesenteric adipose tissue inflammation compared to low-fat diets (10% Kcal, as reflected by increased expression of osteopontin and interferon-gamma. Immune responses to dietary OVA further increased diet-induced osteopontin and interferon-gamma expression in mesenteric adipose. Inflammatory gene expression in subcutaneous tissue did not respond significantly to OVA or dietary fat content. Lastly, whereas OVA responses did not significantly affect bodyweight or adiposity, they significantly impaired glucose tolerance. CONCLUSIONS/SIGNIFICANCE: Our results suggest that loss or lack of immunological tolerance to intestinally absorbed T-lymphocyte antigens can contribute to mesenteric adipose tissue inflammation and defective glucose metabolism

  8. Giardia duodenalis Infection Reduces Granulocyte Infiltration in an In Vivo Model of Bacterial Toxin-Induced Colitis and Attenuates Inflammation in Human Intestinal Tissue

    OpenAIRE

    Cotton, James A.; Motta, Jean-Paul; Schenck, L. Patrick; Hirota, Simon A.; Beck, Paul L.; Buret, Andre G.

    2014-01-01

    Giardia duodenalis (syn. G. intestinalis, G. lamblia) is a predominant cause of waterborne diarrheal disease that may lead to post-infectious functional gastrointestinal disorders. Although Giardia-infected individuals could carry as much as 106 trophozoites per centimetre of gut, their intestinal mucosa is devoid of overt signs of inflammation. Recent studies have shown that in endemic countries where bacterial infectious diseases are common, Giardia infections can protect against the develo...

  9. Green tea, cocoa, and red wine polyphenols moderately modulate intestinal inflammation and do not increase high-density lipoprotein (HDL) production.

    Science.gov (United States)

    Nicod, Nathalie; Chiva-Blanch, Gemma; Giordano, Elena; Dávalos, Alberto; Parker, Robert S; Visioli, Francesco

    2014-03-12

    Although polyphenols are often merely perceived as antioxidants, their biological activities are manifold and include anti-inflammatory actions. A new area of research on polyphenols and health concerns their putative role in cholesterol metabolism, in particular, their high-density lipoprotein-cholesterol (HDL-c)-raising potential. Indeed, some human studies showed that administration of polyphenol-rich foods such as cocoa, green tea, and extra virgin olive oil modulate and increase HDL-c concentrations. This study assessed the effects of polyphenols on intestinal inflammation, using the physiologically relevant Caco-2 Transwell model and using lipopolysaccharide (LPS) to trigger inflammation. This study also investigated the mechanisms of actions behind the proposed HDL-c-increasing effects of polyphenols. The data suggest that polyphenols (at least those from red wine, cocoa, and green tea) administered at a dietary dose moderately modulate intestinal inflammation but do not increase cholesterol secretion by intestinal cells or enhance HDL functionality. Nutraceuticals and supplements provide pharmanutritional doses that might, conversely, produce beneficial effects.

  10. Dietary Fiber Intake Regulates Intestinal Microflora and Inhibits Ovalbumin-Induced Allergic Airway Inflammation in a Mouse Model.

    Science.gov (United States)

    Zhang, Zhiyu; Shi, Lei; Pang, Wenhui; Liu, Wenwen; Li, Jianfeng; Wang, Haibo; Shi, Guanggang

    2016-01-01

    Recently, academic studies suggest that global growth of airway allergic disease has a close association with dietary changes including reduced consumption of fiber. Therefore, appropriate dietary fiber supplementation might be potential to prevent airway allergic disease (AAD). We investigated whether dietary fiber intake suppressed the induction of AAD and tried to elucidate the possible underlying mechanisms. The control mice and AAD model mice fed with 4% standard-fiber chow, while low-fiber group of mice fed with a 1.75% low-fiber chow. The two fiber-intervened groups including mice, apart from a standard-fiber diet, were also intragastric (i.g.) administrated daily with poorly fermentable cellulose or readily fermentable pectin (0.4% of daily body weight), respectively. All animals except normal mice were sensitized and challenged with ovalbumin (OVA) to induce airway allergic inflammation. Hallmarks of AAD were examined by histological analysis and ELISA. The variation in intestinal bacterial composition was assessed by qualitative analysis of 16S ribosomal DNA (rDNA) content in fecal samples using real-time PCR. Low-fiber diet aggravated inflammatory response in ovalbumin-induced allergic mice, whereas dietary fiber intake significantly suppressed the allergic responses, attenuated allergic symptoms of nasal rubbing and sneezing, decreased the pathology of eosinophil infiltration and goblet cell metaplasia in the nasal mucosa and lung, inhibited serum OVA-specific IgE levels, and lowered the levels of Th2 cytokines in NALF and BALF, but, increased Th1 (IFN-γ) cytokines. Additionally, dietary fiber intake also increased the proportion of Bacteroidetes and Actinobacteria, and decreased Firmicutes and Proteobacteria. Levels of probiotic bacteria, such as Lactobacillus and Bifidobacterium, were upgraded significantly. Long-term deficiency of dietary fiber intake increases the susceptibility to AAD, whereas proper fiber supplementation promotes effectively the

  11. Respiratory influenza virus infection induces intestinal immune injury via microbiota-mediated Th17 cell–dependent inflammation

    Science.gov (United States)

    Wang, Jian; Li, Fengqi; Wei, Haiming; Lian, Zhe-Xiong; Sun, Rui

    2014-01-01

    Influenza in humans is often accompanied by gastroenteritis-like symptoms such as diarrhea, but the underlying mechanism is not yet understood. We explored the occurrence of gastroenteritis-like symptoms using a mouse model of respiratory influenza infection. We found that respiratory influenza infection caused intestinal injury when lung injury occurred, which was not due to direct intestinal viral infection. Influenza infection altered the intestinal microbiota composition, which was mediated by IFN-γ produced by lung-derived CCR9+CD4+ T cells recruited into the small intestine. Th17 cells markedly increased in the small intestine after PR8 infection, and neutralizing IL-17A reduced intestinal injury. Moreover, antibiotic depletion of intestinal microbiota reduced IL-17A production and attenuated influenza-caused intestinal injury. Further study showed that the alteration of intestinal microbiota significantly stimulated IL-15 production from intestinal epithelial cells, which subsequently promoted Th17 cell polarization in the small intestine in situ. Thus, our findings provide new insights into an undescribed mechanism by which respiratory influenza infection causes intestinal disease. PMID:25366965

  12. Melatonin prevents inflammation and oxidative stress caused by abdominopelvic and total body irradiation of rat small intestine.

    Science.gov (United States)

    Guney, Y; Hicsonmez, A; Uluoglu, C; Guney, H Z; Ozel Turkcu, U; Take, G; Yucel, B; Caglar, G; Bilgihan, A; Erdogan, D; Nalca Andrieu, M; Kurtman, C; Zengil, H

    2007-10-01

    We investigated the day-night differences in intestinal oxidative-injury and the inflammatory response following total body (TB) or abdominopelvic (AP) irradiation, and the influence of melatonin administration on tissue injury induced by radiation. Rats (male Wistar, weighing 220-280 g) in the irradiated groups were exposed to a dose of 8 Gy to the TB or AP region in the morning (resting period - 1 h after light onset) or evening (activity span - 13 h after light onset). Vehicle or melatonin was administered immediately before, immediately after and 24 h after irradiation (10, 2.0 and 10 mg/kg, ip, respectively) to the irradiated rats. AP (P < 0.05) and TB (P < 0.05) irradiation applied in the morning caused a significant increase in thiobarbituric acid reactive substance (TBARS) levels. Melatonin treatment in the morning (P < 0.05) or evening (P < 0.05) decreased TBARS levels after TB irradiation. After AP irradiation, melatonin treatment only in the morning caused a significant decrease in TBARS levels (P < 0.05). Although we have confirmed the development of inflammation after radiotherapy by histological findings, neither AP nor TB irradiation caused any marked changes in myeloperoxidase activity in the morning or evening. Our results indicate that oxidative damage is more prominent in rats receiving TB and AP irradiation in the morning and melatonin appears to have beneficial effects on oxidative damage irrespective of the time of administration. Increased neutrophil accumulation indicates that melatonin administration exerts a protective effect on AP irradiation-induced tissue oxidative injury, especially in the morning.

  13. Melatonin prevents inflammation and oxidative stress caused by abdominopelvic and total body irradiation of rat small intestine

    Directory of Open Access Journals (Sweden)

    Y. Guney

    2007-10-01

    Full Text Available We investigated the day-night differences in intestinal oxidative-injury and the inflammatory response following total body (TB or abdominopelvic (AP irradiation, and the influence of melatonin administration on tissue injury induced by radiation. Rats (male Wistar, weighing 220-280 g in the irradiated groups were exposed to a dose of 8 Gy to the TB or AP region in the morning (resting period - 1 h after light onset or evening (activity span - 13 h after light onset. Vehicle or melatonin was administered immediately before, immediately after and 24 h after irradiation (10, 2.0 and 10 mg/kg, ip, respectively to the irradiated rats. AP (P < 0.05 and TB (P < 0.05 irradiation applied in the morning caused a significant increase in thiobarbituric acid reactive substance (TBARS levels. Melatonin treatment in the morning (P < 0.05 or evening (P < 0.05 decreased TBARS levels after TB irradiation. After AP irradiation, melatonin treatment only in the morning caused a significant decrease in TBARS levels (P < 0.05. Although we have confirmed the development of inflammation after radiotherapy by histological findings, neither AP nor TB irradiation caused any marked changes in myeloperoxidase activity in the morning or evening. Our results indicate that oxidative damage is more prominent in rats receiving TB and AP irradiation in the morning and melatonin appears to have beneficial effects on oxidative damage irrespective of the time of administration. Increased neutrophil accumulation indicates that melatonin administration exerts a protective effect on AP irradiation-induced tissue oxidative injury, especially in the morning.

  14. Inhibition of Epithelial TNF-α Receptors by Purified Fruit Bromelain Ameliorates Intestinal Inflammation and Barrier Dysfunction in Colitis.

    Science.gov (United States)

    Zhou, Zijuan; Wang, Liang; Feng, Panpan; Yin, Lianhong; Wang, Chen; Zhi, Shengxu; Dong, Jianyi; Wang, Jingyu; Lin, Yuan; Chen, Dapeng; Xiong, Yongjian; Peng, Jinyong

    2017-01-01

    Activation of the TNF-α receptor (TNFR) leads to an inflammatory response, and anti-TNF therapy has been administered to reduce inflammation symptoms and heal mucosal ulcers in inflammatory bowel disease (IBD). Bromelain, a complex natural mixture of proteolytic enzymes, has been shown to exert anti-inflammatory effects. This study aimed to investigate the effect of purified fruit bromelain (PFB)-induced inhibition of epithelial TNFR in a rat colitis model. Colitis was established by intracolonic administration of 2, 4, 6-trinitrobenzene sulfonic acid. Expression of TNFR1 and TNFR2 was measured by quantitative RT-PCR and western blotting. The effect of PFB on colitis was evaluated by examining the inflammatory response and intestinal epithelial barrier function. Our results showed that both TNFR1 and TNFR2 expression were significantly increased in a colitis model, and the increase was significantly reversed by PFB. Colitis symptoms, including infiltration of inflammatory cells, cytokine profiles, epithelial cell apoptosis, and epithelial tight junction barrier dysfunction were significantly ameliorated by PFB. Compared with fruit bromelain and stem bromelain complex, the inhibition of TNFR2 induced by PFB was stronger than that exhibited on TNFR1. These results indicate that PFB showed a stronger selective inhibitory effect on TNFR2 than TNFR1. In other words, purification of fruit bromelain increases its selectivity on TNFR2 inhibition. High expression of epithelial TNFRs in colitis was significantly counteracted by PFB, and PFB-induced TNFR inhibition ameliorated colitis symptoms. These results supply novel insights into potential IBD treatment by PFB.

  15. Regulation of Toll-like receptors-mediated inflammation by immunobiotics in bovine intestinal epitheliocytes: role of signalling pathways and negative regulators

    Directory of Open Access Journals (Sweden)

    Julio eVillena

    2014-09-01

    Full Text Available Intestinal epithelial cells (IECs detect bacterial and viral associated-molecular-patterns (MAMPs via germline-encoded pattern-recognition receptors (PRRs and are responsible for maintaining immunetolerance to the communities of resident commensal bacteria while being also capable to mount immune responses against pathogens. Toll-like receptors (TLRs are a major class of PRRs expressed on IECs and immune cells, which are involved in the induction of both tolerance and inflammation. In the last decade, experimental and clinical evidence was generated to support the application of probiotics with immunoregulatory capacities (immunobiotics for the prevention and treatment of several gastrointestinal inflammatory disorders in which TLRs exert a significant role. The majority of these studies were performed in mouse and human cell lines and, despite the growing interest in the bovine immune system due to the economic importance of cattle as livestock, only few studies have been conducted on cattle. In this regard, our group have established a bovine intestinal epithelial (BIE cell line originally derived from fetal bovine intestinal epitheliocytes and used this cell line to evaluate the impact of immunobiotics in TLR-mediated inflammation. This review aims to summarize the current knowledge of the beneficial effects of immunobiotics in the regulation of intestinal inflammation/infection in cattle. Especially we discuss the role of TLRs and their negative regulators in both the inflammatory response nd the beneficial effects of immunobiotics in bovine IECs. This review article emphasizes the cellular and molecular interactions of immunobiotics with BIE cells through TLRs and gives the scientific basis for the development of immunomodulatory feed for bovine healthy development.

  16. Cannabinoid receptor-specific mechanisms to alleviate pain in sickle cell anemia via inhibition of mast cell activation and neurogenic inflammation.

    Science.gov (United States)

    Vincent, Lucile; Vang, Derek; Nguyen, Julia; Benson, Barbara; Lei, Jianxun; Gupta, Kalpna

    2016-05-01

    Sickle cell anemia is a manifestation of a single point mutation in hemoglobin, but inflammation and pain are the insignia of this disease which can start in infancy and continue throughout life. Earlier studies showed that mast cell activation contributes to neurogenic inflammation and pain in sickle mice. Morphine is the common analgesic treatment but also remains a major challenge due to its side effects and ability to activate mast cells. We, therefore, examined cannabinoid receptor-specific mechanisms to mitigate mast cell activation, neurogenic inflammation and hyperalgesia, using HbSS-BERK sickle and cannabinoid receptor-2-deleted sickle mice. We show that cannabinoids mitigate mast cell activation, inflammation and neurogenic inflammation in sickle mice via both cannabinoid receptors 1 and 2. Thus, cannabinoids influence systemic and neural mechanisms, ameliorating the disease pathobiology and hyperalgesia in sickle mice. This study provides 'proof of principle' for the potential of cannabinoid/cannabinoid receptor-based therapeutics to treat several manifestations of sickle cell anemia. Copyright© Ferrata Storti Foundation.

  17. Expression and distribution patterns of Mas-related gene receptor subtypes A-H in the mouse intestine: inflammation-induced changes.

    Science.gov (United States)

    Avula, Leela Rani; Buckinx, Roeland; Favoreel, Herman; Cox, Eric; Adriaensen, Dirk; Van Nassauw, Luc; Timmermans, Jean-Pierre

    2013-05-01

    Mas-related gene (Mrg) receptors constitute a subfamily of G protein-coupled receptors that are implicated in nociception, and are as such considered potential targets for pain therapies. Furthermore, some Mrgs have been suggested to play roles in the regulation of inflammatory responses to non-immunological activation of mast cells and in mast cell-neuron communication. Except for MrgD, E and F, whose changed expression has been revealed during inflammation in the mouse intestine in our earlier studies, information concerning the remaining cloned mouse Mrg subtypes in the gastrointestinal tract during (patho) physiological conditions is lacking. Therefore, the present study aimed at identifying the presence and putative function of these remaining cloned Mrg subtypes (n = 19) in the (inflamed) mouse intestine. Using reverse transcriptase-PCR, quantitative-PCR and multiple immunofluorescence staining with commercial and newly custom-developed antibodies, we compared the ileum and the related dorsal root ganglia (DRG) of non-inflamed mice with those of two models of intestinal inflammation, i.e., intestinal schistosomiasis and 2,4,6-trinitrobenzene sulfonic acid-induced ileitis. In the non-inflamed ileum and DRG, the majority of the Mrg subtypes examined were sparsely expressed, showing a neuron-specific expression pattern. However, significant changes in the expression patterns of multiple Mrg subtypes were observed in the inflamed ileum; for instance, MrgA4, MrgB2and MrgB8 were expressed in a clearly increased number of enteric sensory neurons and in nerve fibers in the lamina propria, while de novo expression of MrgB10 was observed in enteric sensory neurons and in newly recruited mucosal mast cells (MMCs). The MrgB10 expressing MMCs were found to be in close contact with nerve fibers in the lamina propria. This is the first report on the expression of all cloned Mrg receptor subtypes in the (inflamed) mouse intestine. The observed changes in the expression and

  18. Early administration of probiotic Lactobacillus acidophilus and/or prebiotic inulin attenuates pathogen-mediated intestinal inflammation and Smad 7 cell signaling

    Science.gov (United States)

    Foye, Ondulla T.; Huang, I-Fei; Chiou, Christine C.; Walker, W. Allan; Shi, Hai Ning

    2014-01-01

    Immaturity of gut-associated immunity may contribute to pediatric mortality associated with enteric infections. A murine model to parallel infantile enteric disease was used to determine the effects of probiotic, Lactobacillus acidophilus (La), prebiotic, inulin, or both (synbiotic, syn) on pathogen-induced inflammatory responses, NF-κB, and Smad 7 signaling. Newborn mice were inoculated bi-weekly for 4 weeks with La, inulin, or syn and challenged with Citrobacter rodentium (Cr) at 5 weeks. Mouse intestinal epithelial cells (CMT93) were exposed to Cr to determine temporal alterations in NF-Kappa B and Smad 7 levels. Mice with pretreatment of La, inulin, and syn show reduced intestinal inflammation following Cr infection compared with controls, which is associated with significantly reduced bacterial colonization in La, inulin, and syn animals. Our results further show that host defense against Cr infection correlated with enhanced colonic IL-10 and transforming growth factor-β expression and inhibition of NF-κB in syn-treated mice, whereas mice pretreated with syn, La, or inulin had attenuation of Cr-induced Smad 7 expression. There was a temporal Smad 7 and NF-κB intracellular accumulation post-Cr infection and post-tumor necrosis factor stimulation in CMT93 cells. These results, therefore, suggest that probiotic, La, prebiotic inulin, or synbiotic may promote host-protective immunity and attenuate Cr-induced intestinal inflammation through mechanisms affecting NF-κB and Smad 7 signaling. PMID:22524476

  19. Deoxynivalenol impairs hepatic and intestinal gene expression of selected oxidative stress, tight junction and inflammation proteins in broiler chickens, but addition of an adsorbing agent shifts the effects to the distal parts of the small intestine.

    Science.gov (United States)

    Osselaere, Ann; Santos, Regiane; Hautekiet, Veerle; De Backer, Patrick; Chiers, Koen; Ducatelle, Richard; Croubels, Siska

    2013-01-01

    Broiler chickens are rather resistant to deoxynivalenol and thus, clinical signs are rarely seen. However, effects of subclinical concentrations of deoxynivalenol on both the intestine and the liver are less frequently studied at the molecular level. During our study, we investigated the effects of three weeks of feeding deoxynivalenol on the gut wall morphology, intestinal barrier function and inflammation in broiler chickens. In addition, oxidative stress was evaluated in both the liver and intestine. Besides, the effect of a clay-based mycotoxin adsorbing agent on these different aspects was also studied. Our results show that feeding deoxynivalenol affects the gut wall morphology both in duodenum and jejenum of broiler chickens. A qRT-PCR analysis revealed that deoxynivalenol acts in a very specific way on the intestinal barrier, since only an up-regulation in mRNA expression of claudin 5 in jejunum was observed, while no effects were seen on claudin 1, zona occludens 1 and 2. Addition of an adsorbing agent resulted in an up-regulation of all the investigated genes coding for the intestinal barrier in the ileum. Up-regulation of Toll-like receptor 4 and two markers of oxidative stress (heme-oxigenase or HMOX and xanthine oxidoreductase or XOR) were mainly seen in the jejunum and to a lesser extent in the ileum in response to deoxynivalenol, while in combination with an adsorbing agent main effect was seen in the ileum. These results suggest that an adsorbing agent may lead to higher concentrations of deoxynivalenol in the more distal parts of the small intestine. In the liver, XOR was up-regulated due to DON exposure. HMOX and HIF-1α (hypoxia-inducible factor 1α) were down-regulated due to feeding DON but also due to feeding the adsorbing agent alone or in combination with DON.

  20. Deoxynivalenol impairs hepatic and intestinal gene expression of selected oxidative stress, tight junction and inflammation proteins in broiler chickens, but addition of an adsorbing agent shifts the effects to the distal parts of the small intestine.

    Directory of Open Access Journals (Sweden)

    Ann Osselaere

    Full Text Available Broiler chickens are rather resistant to deoxynivalenol and thus, clinical signs are rarely seen. However, effects of subclinical concentrations of deoxynivalenol on both the intestine and the liver are less frequently studied at the molecular level. During our study, we investigated the effects of three weeks of feeding deoxynivalenol on the gut wall morphology, intestinal barrier function and inflammation in broiler chickens. In addition, oxidative stress was evaluated in both the liver and intestine. Besides, the effect of a clay-based mycotoxin adsorbing agent on these different aspects was also studied. Our results show that feeding deoxynivalenol affects the gut wall morphology both in duodenum and jejenum of broiler chickens. A qRT-PCR analysis revealed that deoxynivalenol acts in a very specific way on the intestinal barrier, since only an up-regulation in mRNA expression of claudin 5 in jejunum was observed, while no effects were seen on claudin 1, zona occludens 1 and 2. Addition of an adsorbing agent resulted in an up-regulation of all the investigated genes coding for the intestinal barrier in the ileum. Up-regulation of Toll-like receptor 4 and two markers of oxidative stress (heme-oxigenase or HMOX and xanthine oxidoreductase or XOR were mainly seen in the jejunum and to a lesser extent in the ileum in response to deoxynivalenol, while in combination with an adsorbing agent main effect was seen in the ileum. These results suggest that an adsorbing agent may lead to higher concentrations of deoxynivalenol in the more distal parts of the small intestine. In the liver, XOR was up-regulated due to DON exposure. HMOX and HIF-1α (hypoxia-inducible factor 1α were down-regulated due to feeding DON but also due to feeding the adsorbing agent alone or in combination with DON.

  1. Dietary intervention with green dwarf banana flour (Musa sp AAA) prevents intestinal inflammation in a trinitrobenzenesulfonic acid model of rat colitis.

    Science.gov (United States)

    Scarminio, Viviane; Fruet, Andrea C; Witaicenis, Aline; Rall, Vera L M; Di Stasi, Luiz C

    2012-03-01

    Dietary products are among the therapeutic approaches used to modify intestinal microflora and to promote protective effects during the intestinal inflammatory process. Because the banana plant is rich in resistant starch, which is used by colonic microbiota for the anaerobic production of the short-chain fatty acids that serve as a major fuel source for colonocytes: first, green dwarf banana flour produces protective effects on the intestinal inflammation acting as a prebiotic and, second, combination of this dietary supplementation with prednisolone presents synergistic effects. For this, we used the trinitrobenzenesulphonic acid (TNBS) model of rat colitis. Our results revealed that the protective effect produced by a combination of 10% green dwarf banana flour with prednisolone was more pronounced than those promoted by a single administration of prednisolone or a diet containing 10% or 20% banana flour. This beneficial effect was associated with an improvement in the colonic oxidative status because the banana flour diet prevented the glutathione depletion and inhibited myeloperoxidase activity and lipid peroxidation. In addition, the intestinal anti-inflammatory activity was associated with an inhibition of alkaline phosphatase activity, a reduction in macroscopic and microscopic scores, and an extension of the lesions. In conclusion, the dietary use of the green dwarf banana flour constitutes an important dietary supplement and complementary medicine product to prevention and treatment of human inflammatory bowel disease. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Protective effect of the essential oil of Zanthoxylum myriacanthum var. pubescens against dextran sulfate sodium-induced intestinal inflammation in mice.

    Science.gov (United States)

    Ji, Kai-Long; Gan, Xiao-Qing; Xu, You-Kai; Li, Xiu-Fen; Guo, Juan; Dahab, Mahmoud M; Zhang, Ping

    2016-08-15

    Zanthoxylum myriacanthum var. pubescens is an ethnic medicine for digestive disease known as Maqian. A previous report showed that the Maqian fruits essential oil (MQEO) exhibited an NO inhibitory effect on RAW 264.7 cells, but the effect on inflammatory disease in vivo remains unknown. To investigate the anti-inflammatory effect of Z. myriacanthum var. pubescens as potential candidate for the treatment of intestinal inflammation. Evaluation of anti-inflammatory effect of MQEO using dextran sulfate sodium (DSS)-induced intestinal inflammation in mice and exploration of the mechanisms with THP-1 cells. C57BL/6 mice were provided drinking water containing 3% DSS for 10 days followed by normal drinking water for 3 days. MQEO (35 and 70mg/kg) were given 5 days before experiments and continued for another 13 days. At the end of experiments, mice were euthanized and colonic tissue was collected to be analyzed by H&E staining, RT-PCR and immunohistochemistry for evaluating the damage of colons, the mRNA levels of IL-1β, IL-6, IL-12p35 and TNF-α, and the expressions of myeloperoxidase (MPO) and matrix metalloproteinase-9 (MMP-9). The LPS-stimulated THP-1 cell line was used for exploring the role of inflammatory markers using ELISA, western blot and flow cytometry methods. Oral administration of MQEO (35 and 70mg/kg) markedly attenuated the symptoms of intestinal inflammation, including diarrhea, rectal bleeding, and loss of body weight. It also reduced the shortening of colon length and histopathological damage. The expressions of MPO and MMP-9 and the mRNA levels of pro-inflammatory cytokines (IL-1β, IL-6 and IL-12p35) in colonic tissue significantly decreased after MQEQ treatment. The activation of NF-κB p65 in colonic mucosa was also markedly suppressed. In addition, MQEO significantly suppressed LPS-stimulated production of TNF-α and IL-1β, effectively blocked phosphorylation of IKK and IκB, and dose-dependently reduced LPS-stimulated expression of TLR4 in THP-1

  3. Retinoic acid signalling is required for the efficient differentiation of CD4+ T cells into pathogenic effector cells during the development of intestinal inflammation

    DEFF Research Database (Denmark)

    Rivollier, Aymeric Marie Christian; Pool, Lieneke; Frising, Ulrika

    Epidemiological studies of vitamin A-deficient populations have illustrated the importance of the vitamin A metabolite retinoic acid (RA) in mucosal immune responses. However, RA seems to be a double-edge sword in CD4+ T cell biology. While it sustains the development of foxp3+ regulatory T cells......-deficient CD4+ T cells are less potent at inducing intestinal inflammation compared to their RA signalling-competent counterparts and exhibit a differentiation skewing towards more IFNγ- IL-17+, IL-17+IFNγ+ and foxp3+ cells, while their capacity to differentiate into IL-17-IFNγ+ Th1 cells is compromised...

  4. Intraluminal Tranexamic Acid Inhibits Intestinal Sheddases and Mitigates Gut and Lung Injury and Inflammation in a Rodent Model of Hemorrhagic Shock

    Science.gov (United States)

    Peng, Zhanglong; Ban, Kechen; LeBlanc, Anthony; Kozar, Rosemary Ann

    2016-01-01

    Background Intravenous tranexamic acid (TXA) is an effective adjunct after hemorrhagic shock (HS) due to its antifibrinolytic properties. TXA is also a serine protease inhibitor and recent laboratory data demonstrated that intraluminal TXA into the small bowel inhibited digestive proteases and protected the gut. .ADAM-17 and TNFα are effective sheddases of intestinal syndecan-1 which when shed, exposes the underlying intestinal epithelium to digestive proteases and subsequent systemic insult. We therefore hypothesized that intraluminal TXA as a serine protease inhibitor would reduce intestinal sheddases and syndecan-1 shedding, mitigating gut and distant organ (lung) damage. Methods Mice underwent 90 minutes of hemorrhagic shock to a mean arterial pressure of 35±5 mm Hg following by the intraluminal administration of TXA or vehicle. After 3 hours, small intestine, lung, and blood were collected for analysis. Results Intraluminal TXA significantly reduced gut and lung histopathologic injury and inflammation compared to hemorrhagic shock alone. Gut, lung, and systemic ADAM-17 and TNFα were significantly increased by hemorrhagic shock but lessened by TXA. Additionally, gut and lung syndecan-1 immunostaining were preserved and systemic shedding lessened after TXA. TXA reduced ADAM-17 and TNFα, but not syndecan-1, in TXA-sham animals compared to sham vehicles. Conclusions Results of the present study demonstrate a beneficial effect of intraluminal TXA in the gut and lung after experimental hemorrhagic shock in part due to inhibition of the syndecan-1 shedding by ADAM-17 and TNFα. Further studies are needed to determine if orally administered TXA could provide similar intestinal protection and thus be of potential benefit to patients with survivable hemorrhage at risk for organ injury. This is particularly relevant in patients or soldiers who may not have access to timely medical care. Level of evidence NA PMID:27027557

  5. Osthole Alleviates Bleomycin-Induced Pulmonary Fibrosis via Modulating Angiotensin-Converting Enzyme 2/Angiotensin-(1-7) Axis and Decreasing Inflammation Responses in Rats.

    Science.gov (United States)

    Hao, Yuewen; Liu, Yan

    2016-01-01

    Studies have shown that angiotensin-converting enzyme 2 (ACE2) plays modulating roles in lung pathophysiology, including pulmonary fibrosis (PF) and acute lung injury. Pulmonary fibrosis is a common complication in these interstitial lung diseases, and PF always has a poor prognosis and short survival. To date, there are few promising methods for treating PF, and they are invariably accompanied by severe side effects. Recent studies have showed that the traditional Chinese herbal extract, osthole, had beneficial effects on lipopolysaccharide (LPS) induced acute lung injury (ALI) via an ACE2 pathway. Here we further investigated the protective effects of osthole on bleomycin induced pulmonary fibrosis and attempted to determine the underlying mechanism. PF mode rats were induced by bleomycin (BLM) and then subsequently administered osthole. Histopathological analyses were employed to identify PF changes. The results showed that BLM resulted in severe PF and diffuse lung inflammation, together with significant elevation of inflammatory factors and a marked increase in expression of angiotensin II (ANG II) and transforming growth factor-beta 1 (TGF-β1). ACE2 and angiotensin-(1-7) [ANG-(1-7)] were both greatly reduced after BLM administration. Meanwhile, osthole treatment attenuated BLM induced PF and inflammation, decreased the expression of these inflammatory mediators, ANG II, and TGF-β1, and reversed ACE2 and ANG-(1-7) production in rat lungs. We conclude that osthole may exert beneficial effects on BLM induced PF in rats, perhaps via modulating the ACE2/ANG-(1-7) axis and inhibiting lung inflammation pathways.

  6. Disruption of the Circadian Clock in Mice Increases Intestinal Permeability and Promotes Alcohol-Induced Hepatic Pathology and Inflammation.

    Directory of Open Access Journals (Sweden)

    Keith C Summa

    Full Text Available The circadian clock orchestrates temporal patterns of physiology and behavior relative to the environmental light:dark cycle by generating and organizing transcriptional and biochemical rhythms in cells and tissues throughout the body. Circadian clock genes have been shown to regulate the physiology and function of the gastrointestinal tract. Disruption of the intestinal epithelial barrier enables the translocation of proinflammatory bacterial products, such as endotoxin, across the intestinal wall and into systemic circulation; a process that has been linked to pathologic inflammatory states associated with metabolic, hepatic, cardiovascular and neurodegenerative diseases - many of which are commonly reported in shift workers. Here we report, for the first time, that circadian disorganization, using independent genetic and environmental strategies, increases permeability of the intestinal epithelial barrier (i.e., gut leakiness in mice. Utilizing chronic alcohol consumption as a well-established model of induced intestinal hyperpermeability, we also found that both genetic and environmental circadian disruption promote alcohol-induced gut leakiness, endotoxemia and steatohepatitis, possibly through a mechanism involving the tight junction protein occludin. Circadian organization thus appears critical for the maintenance of intestinal barrier integrity, especially in the context of injurious agents, such as alcohol. Circadian disruption may therefore represent a previously unrecognized risk factor underlying the susceptibility to or development of alcoholic liver disease, as well as other conditions associated with intestinal hyperpermeability and an endotoxin-triggered inflammatory state.

  7. Ethyl-cellulose rumen-protected methionine alleviates inflammation and oxidative stress and improves neutrophil function during the periparturient period and early lactation in Holstein dairy cows.

    Science.gov (United States)

    Batistel, F; Arroyo, J M; Garces, C I M; Trevisi, E; Parys, C; Ballou, M A; Cardoso, F C; Loor, J J

    2018-01-01

    The periparturient period is the most critical phase in the productive cycle of dairy cows and is characterized by impairment of the immune system. Our objective was to evaluate the effect of feeding ethyl-cellulose rumen-protected methionine (RPM) starting at d -28 from expected parturition through 60 d in milk on biomarkers of inflammation, oxidative stress, and liver function as well as leukocyte function. Sixty multiparous Holstein cows were used in a block design and assigned to either a control or the control plus ethyl-cellulose RPM (Mepron, Evonik Nutrition & Care GmbH). Mepron was supplied from -28 to 60 d in milk at a rate of 0.09% and 0.10% dry matter during the prepartum and postpartum period. That rate ensured that the ratio of Lys to Met in the metabolizable protein was close to 2.8:1. Blood samples from 15 clinically healthy cows per treatment were collected at d -30, -14, 1, 7, 21, 30, and 60 and analyzed for biomarkers of liver function, inflammation, and oxidative stress. Neutrophil and monocyte function in whole blood was measured in vitro at -14, 1, 7, 21, and 30 d in milk. The statistical model included the random effect of block and fixed effect of treatment, time, and its interaction. Compared with control, ethyl-cellulose RPM increased plasma cholesterol and paraoxonase after parturition. Among the inflammation biomarkers measured, ethyl-cellulose RPM led to greater albumin (negative acute-phase protein) and lower haptoglobin than control cows. Although concentration of IL-1β was not affected by treatments, greater IL-6 concentration was detected in response to ethyl-cellulose RPM. Cows supplemented with ethyl-cellulose RPM had greater plasma concentration of ferric-reducing antioxidant power, β-carotene, tocopherol, and total and reduced glutathione, whereas reactive oxygen metabolites were lower compared with control cows. Compared with control, ethyl-cellulose RPM enhanced neutrophil phagocytosis and oxidative burst. Overall, the

  8. Blockage of glycolysis by targeting PFKFB3 alleviates sepsis-related acute lung injury via suppressing inflammation and apoptosis of alveolar epithelial cells.

    Science.gov (United States)

    Gong, Yuanqi; Lan, Haibing; Yu, Zhihong; Wang, Meng; Wang, Shu; Chen, Yu; Rao, Haiwei; Li, Jingying; Sheng, Zhiyong; Shao, Jianghua

    2017-09-16

    Sepsis-related acute lung injury (ALI) is characterized by excessive lung inflammation and apoptosis of alveolar epithelial cells resulting in acute hypoxemic respiratory failure. Recent studies indicated that anaerobic glycolysis play an important role in sepsis. However, whether inhibition of aerobic glycolysis exhibits beneficial effect on sepsis-induced ALI is not known. In vivo, a cecal ligation and puncture (CLP)-induced ALI mouse model was set up and mice treated with glycolytic inhibitor 3PO after CLP. The mice treated with the 3PO ameliorated the survival rate, histopathological changes, lung inflammation, lactate increased and lung apoptosis of mice with CLP-induced sepsis. In vitro, the exposure of human alveolar epithelial A549 cells to lipopolysaccharide (LPS) resulted in cell apoptosis, inflammatory cytokine production, enhanced glycolytic flux and reactive oxygen species (ROS) increased. While these changes were attenuated by 3PO treatment. Sequentially, treatment of A549 cells with lactate caused cell apoptosis and enhancement of ROS. Pretreatment with N-acetylcysteine (NAC) significantly lowered LPS and lactate-induced the generation of ROS and cell apoptosis in A549 cells. Therefore, these results indicate that anaerobic glycolysis may be an important contributor in cell apoptosis of sepsis-related ALI. Moreover, LPS specifically induces apoptotic insults to A549 cell through lactate-mediated enhancement of ROS. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Metabolic changes and inflammation in cultured astrocytes from the 5xFAD mouse model of Alzheimer's disease: Alleviation by pantethine.

    Directory of Open Access Journals (Sweden)

    Manuel van Gijsel-Bonnello

    Full Text Available Astrocytes play critical roles in central nervous system homeostasis and support of neuronal function. A better knowledge of their response may both help understand the pathophysiology of Alzheimer's disease (AD and implement new therapeutic strategies. We used the 5xFAD transgenic mouse model of AD (Tg thereafter to generate astrocyte cultures and investigate the impact of the genotype on metabolic changes and astrocytes activation. Metabolomic analysis showed that Tg astrocytes exhibited changes in the glycolytic pathway and tricarboxylic acid (TCA cycle, compared to wild type (WT cells. Tg astrocytes displayed also a prominent basal inflammatory status, with accentuated reactivity and increased expression of the inflammatory cytokine interleukin-1 beta (IL-1β. Compensatory mechanisms were activated in Tg astrocytes, including: i the hexose monophosphate shunt with the consequent production of reducing species; ii the induction of hypoxia inducible factor-1 alpha (HIF-1α, known to protect against amyloid-β (Aβ toxicity. Such events were associated with the expression by Tg astrocytes of human isoforms of both amyloid precursor protein (APP and presenilin-1 (PS1. Similar metabolic and inflammatory changes were induced in WT astrocytes by exogenous Aβ peptide. Pantethine, the vitamin B5 precursor, known to be neuroprotective and anti-inflammatory, alleviated the pathological pattern in Tg astrocytes as well as WT astrocytes treated with Aß. In conclusion, our data enlighten the dual pathogenic/protective role of astrocytes in AD pathology and the potential protective role of pantethine.

  10. Giardia duodenalis infection reduces granulocyte infiltration in an in vivo model of bacterial toxin-induced colitis and attenuates inflammation in human intestinal tissue.

    Science.gov (United States)

    Cotton, James A; Motta, Jean-Paul; Schenck, L Patrick; Hirota, Simon A; Beck, Paul L; Buret, Andre G

    2014-01-01

    Giardia duodenalis (syn. G. intestinalis, G. lamblia) is a predominant cause of waterborne diarrheal disease that may lead to post-infectious functional gastrointestinal disorders. Although Giardia-infected individuals could carry as much as 106 trophozoites per centimetre of gut, their intestinal mucosa is devoid of overt signs of inflammation. Recent studies have shown that in endemic countries where bacterial infectious diseases are common, Giardia infections can protect against the development of diarrheal disease and fever. Conversely, separate observations have indicated Giardia infections may enhance the severity of diarrheal disease from a co-infecting pathogen. Polymorphonuclear leukocytes or neutrophils (PMNs) are granulocytic, innate immune cells characteristic of acute intestinal inflammatory responses against bacterial pathogens that contribute to the development of diarrheal disease following recruitment into intestinal tissues. Giardia cathepsin B cysteine proteases have been shown to attenuate PMN chemotaxis towards IL-8/CXCL8, suggesting Giardia targets PMN accumulation. However, the ability of Giardia infections to attenuate PMN accumulation in vivo and how in turn this effect may alter the host inflammatory response in the intestine has yet to be demonstrated. Herein, we report that Giardia infection attenuates granulocyte tissue infiltration induced by intra-rectal instillation of Clostridium difficile toxin A and B in an isolate-dependent manner. This attenuation of granulocyte infiltration into colonic tissues paralled decreased expression of several cytokines associated with the recruitment of PMNs. Giardia trophozoite isolates that attenuated granulocyte infiltration in vivo also decreased protein expression of cytokines released from inflamed mucosal biopsy tissues collected from patients with active Crohn's disease, including several cytokines associated with PMN recruitment. These results demonstrate for the first time that certain

  11. Giardia duodenalis infection reduces granulocyte infiltration in an in vivo model of bacterial toxin-induced colitis and attenuates inflammation in human intestinal tissue.

    Directory of Open Access Journals (Sweden)

    James A Cotton

    Full Text Available Giardia duodenalis (syn. G. intestinalis, G. lamblia is a predominant cause of waterborne diarrheal disease that may lead to post-infectious functional gastrointestinal disorders. Although Giardia-infected individuals could carry as much as 106 trophozoites per centimetre of gut, their intestinal mucosa is devoid of overt signs of inflammation. Recent studies have shown that in endemic countries where bacterial infectious diseases are common, Giardia infections can protect against the development of diarrheal disease and fever. Conversely, separate observations have indicated Giardia infections may enhance the severity of diarrheal disease from a co-infecting pathogen. Polymorphonuclear leukocytes or neutrophils (PMNs are granulocytic, innate immune cells characteristic of acute intestinal inflammatory responses against bacterial pathogens that contribute to the development of diarrheal disease following recruitment into intestinal tissues. Giardia cathepsin B cysteine proteases have been shown to attenuate PMN chemotaxis towards IL-8/CXCL8, suggesting Giardia targets PMN accumulation. However, the ability of Giardia infections to attenuate PMN accumulation in vivo and how in turn this effect may alter the host inflammatory response in the intestine has yet to be demonstrated. Herein, we report that Giardia infection attenuates granulocyte tissue infiltration induced by intra-rectal instillation of Clostridium difficile toxin A and B in an isolate-dependent manner. This attenuation of granulocyte infiltration into colonic tissues paralled decreased expression of several cytokines associated with the recruitment of PMNs. Giardia trophozoite isolates that attenuated granulocyte infiltration in vivo also decreased protein expression of cytokines released from inflamed mucosal biopsy tissues collected from patients with active Crohn's disease, including several cytokines associated with PMN recruitment. These results demonstrate for the first time

  12. Dietary intervention with narrow-leaved cattail rhizome flour (Typha angustifolia L. prevents intestinal inflammation in the trinitrobenzenesulphonic acid model of rat colitis

    Directory of Open Access Journals (Sweden)

    Fruet Andréa

    2012-05-01

    Full Text Available Abstract Background Inflammatory bowel disease (IBD is a chronic inflammation of the intestinal epithelium that is driven by the intestinal immune system, oxidative stress and the loss of tolerance to the luminal microbiota. The use of dietary products containing ingredients such as fibres and carbohydrates and/or antioxidant compounds have been used as a therapeutic strategy for intestinal diseases because these products are considered effective in the modulation of the immune system and colonic microbiota. We investigated the beneficial effects of cattail rhizome flour (Typha angustifolia L. in the trinitrobenzenesulphonic acid (TNBS model of rat colitis. In addition, we investigated the effects of cattail rhizome flour on the intestinal anti-inflammatory activity of prednisolone, which is a reference drug that is used for treatment of human IBD. Methods The present study included the preparation of flour from rhizomes of cattail (Typha angustifolia L.; an evaluation of the qualitative phytochemical profile of cattail rhizomes; an evaluation of the efficacy of cattail rhizome flour in TNBS-induced rat colitis; an evaluation of the synergistic effects of cattail rhizome flour on the intestinal anti-inflammatory activity of prednisolone; and macroscopic, clinical, biochemical, histopathological and microbiological studies to assess the healing effects of cattail rhizome flour and its synergistic effects in TNBS-induced rat colitis. The data were analysed by ANOVA, Kruskal-Wallis and χ2 tests. Results We tested several concentrations of cattail rhizome flour and found that dietary supplementation with 10% cattail rhizome flour showed the best effects at reducing the extension of the lesion, the colon weight ratio, adherences to adjacent organs and diarrhoea. These effects were related to inhibition of myeloperoxidase (MPO and alkaline phosphatase (AP activities and an attenuation of glutathione (GSH depletion. The 10% cattail rhizome flour was

  13. Relievable effect of dietary Allium hookeri on LPS-induced intestinal inflammation response in young broiler chickens

    Science.gov (United States)

    A study using 150 one-day- old broilers was conducted to assess the effects of Allium hookeri (AH) root and fermented root on inflammatory responses and intestinal barrier integrity of LPS challenged broiler chickens. Birds were randomly assigned to six groups (n = 25 birds/treatment) and fed standa...

  14. Effects of probiotic Lactobacillus rhamnosus GG and Propionibacterium freudenreichii ssp. shermanii JS supplementation on intestinal and systemic markers of inflammation in ApoE*3Leiden mice consuming a high-fat diet.

    Science.gov (United States)

    Oksaharju, Anna; Kooistra, Teake; Kleemann, Robert; van Duyvenvoorde, Wim; Miettinen, Minja; Lappalainen, Jani; Lindstedt, Ken A; Kovanen, Petri T; Korpela, Riitta; Kekkonen, Riina A

    2013-07-14

    A high-fat diet disturbs the composition and function of the gut microbiota and generates local gut-associated and also systemic responses. Intestinal mast cells, for their part, secrete mediators which play a role in the orchestration of physiological and immunological functions of the intestine. Probiotic bacteria, again, help to maintain the homeostasis of the gut microbiota by protecting the gut epithelium and regulating the local immune system. In the present study, we explored the effects of two probiotic bacteria, Lactobacillus rhamnosus GG (GG) and Propionibacterium freudenreichii spp. shermanii JS (PJS), on high fat-fed ApoE*3Leiden mice by estimating the mast cell numbers and the immunoreactivity of TNF-α and IL-10 in the intestine, as well as plasma levels of several markers of inflammation and parameters of lipid metabolism. We found that mice that received GG and PJS exhibited significantly lower numbers of intestinal mast cells compared with control mice. PJS lowered intestinal immunoreactivity of TNF-α, while GG increased intestinal IL-10. PJS was also observed to lower the plasma levels of markers of inflammation including vascular cell adhesion molecule 1, and also the amount of gonadal adipose tissue. GG lowered alanine aminotransferase, a marker of hepatocellular activation. Collectively, these data demonstrate that probiotic GG and PJS tend to down-regulate both intestinal and systemic pro-inflammatory changes induced by a high-fat diet in this humanised mouse model.

  15. Hydrolysed inulin alleviates the azoxymethane-induced preneoplastic aberrant crypt foci by altering selected intestinal microbiota in Sprague-Dawley rats.

    Science.gov (United States)

    Pattananandecha, Thanawat; Sirilun, Sasithorn; Duangjitcharoen, Yodsawee; Sivamaruthi, Bhagavathi Sundaram; Suwannalert, Prasit; Peerajan, Sartjin; Chaiyasut, Chaiyavat

    2016-09-01

    Context Inulin, a non-digestible carbohydrate isolated from Helianthus tuberosus L. (Asteraceae), has been shown to alter the gut beneficial bacteria including Lactobacillus spp. and Bifidobacteria. Inulin also influences the activities of intestinal microbiota that could prevent the colon cancer development. Objective This study determines the effect of hydrolysed inulin with different degrees of polymerisation on alteration of intestinal microbiota and their activities on azoxymethane (AOM)-induced preneoplastic aberrant crypt foci (ACF) in rats. Materials and methods Seventy-two male Sprague-Dawley rats were randomly divided into six groups (three control and three AOM-treated groups) and the animal were fed with either a normal diet or diet containing 10% of long-chain inulin (InuL) or short-chain inulin (InuS), respectively, for 17 weeks. Colon cancer was induced in rats by injecting AOM subcutaneously at the 8th and 9th week of the study period. At the end of the experiment, cecal contents of rats were examined for selected microbiota, organic acids, putrefactive compounds and microbial enzymes. ACF formation was microscopically examined. Results The inulin diets significantly increased the weight and decreased the pH of the caecal content. The rats fed with InuL-supplemented diet showed approximately 2.9- and 6.8-fold increases in the biomass of Lactobacillus spp. and Bifidobacteria, respectively. Naive and AOM-treated rats fed with inulin-supplemented diet showed ∼1.3- and ∼2.2-fold decreases in the biomass of Escherichia coli and Salmonella enterica serovar Typhi, respectively. Inulins significantly decreased the colonic concentration of phenol, p-cresol and indole. Reduction in the activity of microbial enzymes such as β-glucuronidase, azoreductase and nitroreductase were observed in inulin-treated animals. Reduction in the ACF formation has been observed in inulin-treated groups. Discussion and conclusion The present study demonstrates that dietary

  16. Cathelicidin-WA Improves Intestinal Epithelial Barrier Function and Enhances Host Defense against Enterohemorrhagic Escherichia coli O157:H7 Infection.

    Science.gov (United States)

    Yi, Hongbo; Hu, Wangyang; Chen, Shan; Lu, Zeqing; Wang, Yizhen

    2017-02-15

    Impaired epithelial barrier function disrupts immune homeostasis and increases inflammation in intestines, leading to many intestinal diseases. Cathelicidin peptides suppress intestinal inflammation and improve intestinal epithelial barrier function independently of their antimicrobial activity. In this study, we investigated the effects of Cathelicidin-WA (CWA) on intestinal epithelial barrier function, as well as the underlying mechanism, by using enterohemorrhagic Escherichia coli (EHEC)-infected mice and intestinal epithelial cells. The results showed that CWA attenuated EHEC-induced clinical symptoms and intestinal colitis, as did enrofloxacin (Enro). CWA decreased IL-6 production in the serum, jejunum, and colon of EHEC-infected mice. Additionally, CWA alleviated the EHEC-induced disruption of mucin-2 and goblet cells in the intestine. Interestingly, CWA increased the mucus layer thickness, which was associated with increasing expression of trefoil factor 3, in the jejunum of EHEC-infected mice. CWA increased the expression of tight junction proteins in the jejunum of EHEC-infected mice. Using intestinal epithelial cells and a Rac1 inhibitor in vitro, we demonstrated that the CWA-mediated increases in the tight junction proteins might depend on the Rac1 pathway. Furthermore, CWA improved the microbiota and short-chain fatty acid concentrations in the cecum of EHEC-infected mice. Although Enro and CWA had similar effects on intestinal inflammation, CWA was superior to Enro with regard to improving intestinal epithelial barrier and microbiota in the intestine. In conclusion, CWA attenuated EHEC-induced inflammation, intestinal epithelial barrier damage, and microbiota disruption in the intestine of mice, suggesting that CWA may be an effective therapy for many intestinal diseases. Copyright © 2017 by The American Association of Immunologists, Inc.

  17. 18F-F.D.G. PET imaging of infection and inflammation: intestinal, prosthesis replacements, fibrosis, sarcoidosis, tuberculosis.

    International Nuclear Information System (INIS)

    Fernandez, A.; Cortes, M.; Caresia, A.P.; Juan, R. de; Vidaller, A.; Mana, J.; Martinez-Yelamos, S.; Gamez, C.

    2008-01-01

    Nuclear medicine plays an important role in the evaluation of infection and inflammation. A variety of diagnostic methods are available for imaging this inflammation and infection, most notably computed tomography, 68 Ga scintigraphy or radionuclide labeled leucocytes. Fluorine 18 fluorodeoxyglucose ( 18 F-F.D.G.) is a readily available radiotracer that offers rapid, exquisitely sensitive high-resolution images by positron emission tomography (PET). Inflammation can be acute or chronic, the former showing predominantly neutrophilic granulocyte infiltrates, whereas in the latter, macrophages predominate. F.D.G. uptake in infection is based on the fact that mononuclear cells and granulocytes use large quantities of glucose by way of the hexose monophosphate shunts. 18 F-F.D.G. PET accurately helps diagnose spinal osteomyelitis, diabetic foot and in inflammatory conditions such as sarcoidosis and tuberculosis.(it appears to be useful for defining the extent of disease and monitoring response to treatment). 18 F-F.D.G. PET can also help localize the source of fever of undetermined origin, thereby guiding additional testing. 18 F-F.D.G. PET may be of limited usefulness in postoperative patients and in patients with a failed joint prosthesis or bowel inflammatory disease. In this review, we will focus on the role of 18 F-F.D.G. PET in the management of patients with inflammation or suspected or confirmed infection

  18. Disruption of 5-HT2A receptor-PDZ protein interactions alleviates mechanical hypersensitivity in carrageenan-induced inflammation in rats.

    Science.gov (United States)

    Wattiez, Anne-Sophie; Pichon, Xavier; Dupuis, Amandine; Hernández, Alejandro; Privat, Anne-Marie; Aissouni, Youssef; Chalus, Maryse; Pelissier, Teresa; Eschalier, Alain; Marin, Philippe; Courteix, Christine

    2013-01-01

    Despite common pathophysiological mechanisms, inflammatory and neuropathic pain do not respond equally to the analgesic effect of antidepressants, except for selective serotonin reuptake inhibitors (SSRIs), which show a limited efficacy in both conditions. We previously demonstrated that an interfering peptide (TAT-2ASCV) disrupting the interaction between 5-HT2A receptors and its associated PDZ proteins (e.g. PSD-95) reveals a 5-HT2A receptor-mediated anti-hyperalgesic effect and enhances the efficacy of fluoxetine (a SSRI) in diabetic neuropathic pain conditions in rats. Here, we have examined whether the same strategy would be useful to treat inflammatory pain. Sub-chronic inflammatory pain was induced by injecting λ-carrageenan (100 µl, 2%) into the left hind paw of the rat. Mechanical hyperalgesia was assessed after acute treatment with TAT-2ASCV or/and fluoxetine (SSRI) 2.5 h after λ-carrageenan injection. Possible changes in the level of 5-HT2A receptors and its associated PDZ protein PSD-95 upon inflammation induction were quantified by Western blotting in dorsal horn spinal cord. Administration of TAT-2ASCV peptide (100 ng/rat, intrathecally) but not fluoxetine (10 mg/kg, intraperitoneally) relieves mechanical hyperalgesia (paw pressure test) in inflamed rats. This anti-hyperalgesic effect involves spinal 5-HT2A receptors and GABAergic interneurons as it is abolished by a 5-HT2A antagonist (M100907, 150 ng/rat, intrathecally) and a GABAA antagonist, (bicuculline, 3 µg/rat, intrathecally). We also found a decreased expression of 5-HT2A receptors in the dorsal spinal cord of inflamed animals which could not be rescued by TAT-2ASCV injection, while the amount of PSD-95 was not affected by inflammatory pain. Finally, the coadministration of fluoxetine does not further enhance the anti-hyperalgesic effect of TAT-2ASCV peptide. This study reveals a role of the interactions between 5-HT2A receptors and PDZ proteins in the pathophysiological pathways of

  19. Dysbiosis gut microbiota associated with inflammation and impaired mucosal immune function in intestine of humans with non-alcoholic fatty liver disease.

    Science.gov (United States)

    Jiang, Weiwei; Wu, Na; Wang, Xuemei; Chi, Yujing; Zhang, Yuanyuan; Qiu, Xinyun; Hu, Ying; Li, Jing; Liu, Yulan

    2015-02-03

    Non-alcoholic fatty liver disease (NAFLD) has recently been considered to be under the influence of the gut microbiota, which might exert toxic effects on the human host after intestinal absorption and delivery to the liver via the portal vein. In this study, the composition of the gut microbiota in NAFLD patients and healthy subjects was determined via 16S ribosomal RNA Illumina next-generation sequencing. Among those taxa displaying greater than 0.1% average abundance in all samples, five genera, including Alistipes and Prevotella, were significantly more abundant in the gut microbiota of healthy subjects compared to NAFLD patients. Alternatively, Escherichia, Anaerobacter, Lactobacillus and Streptococcus were increased in the gut microbiota of NAFLD patients compared to healthy subjects. In addition, decreased numbers of CD4+ and CD8+ T lymphocytes and increased levels of TNF-α, IL-6 and IFN-γ were detected in the NAFLD group compared to the healthy group. Furthermore, irregularly arranged microvilli and widened tight junctions were observed in the gut mucosa of the NAFLD patients via transmission electron microscopy. We postulate that aside from dysbiosis of the gut microbiota, gut microbiota-mediated inflammation of the intestinal mucosa and the related impairment in mucosal immune function play an important role in the pathogenesis of NAFLD.

  20. Disruptions of Host Immunity and Inflammation by Giardia Duodenalis: Potential Consequences for Co-Infections in the Gastro-Intestinal Tract.

    Science.gov (United States)

    Cotton, James A; Amat, Christina B; Buret, Andre G

    2015-11-10

    Giardia duodenalis (syn. G. intestinalis, or G. lamblia) is a leading cause of waterborne diarrheal disease that infects hundreds of millions of people annually. Research on Giardia has greatly expanded within the last few years, and our understanding of the pathophysiology and immunology on this parasite is ever increasing. At peak infection, Giardia trophozoites induce pathophysiological responses that culminate in the development of diarrheal disease. However, human data has suggested that the intestinal mucosa of Giardia-infected individuals is devoid of signs of overt intestinal inflammation, an observation that is reproduced in animal models. Thus, our understanding of host inflammatory responses to the parasite remain incompletely understood and human studies and experimental data have produced conflicting results. It is now also apparent that certain Giardia infections contain mechanisms capable of modulating their host's immune responses. As the oral route of Giardia infection is shared with many other gastrointestinal (GI) pathogens, co-infections may often occur, especially in places with poor sanitation and/or improper treatment of drinking water. Moreover, Giardia infections may modulate host immune responses and have been found to protect against the development of diarrheal disease in developing countries. The following review summarizes our current understanding of the immunomodulatory mechanisms of Giardia infections and their consequences for the host, and highlights areas for future research. Potential implications of these immunomodulatory effects during GI co-infection are also discussed.

  1. Chlorogenic Acid Combined with Lactobacillus plantarum 2142 Reduced LPS-Induced Intestinal Inflammation and Oxidative Stress in IPEC-J2 Cells.

    Science.gov (United States)

    Palócz, Orsolya; Pászti-Gere, Erzsébet; Gálfi, Péter; Farkas, Orsolya

    2016-01-01

    This study was carried out to investigate protective effect of chlorogenic acid against lipopolysaccharide-induced inflammation and oxidative stress in intestinal epithelial cells. As a marker of inflammatory response, IL-6, IL-8, TNF-α mRNA and protein levels, furthermore, COX-2 mRNA level were followed up. Intracellular redox status and extracellular H2O2 level were also monitored by two fluorescent assays (DCFH-DA, Amplex Red). Moreover, the effect of gut microbiota metabolites in the above mentioned processes was taken into account in our model using Lactobacillus plantarum 2142 bacterial strain. Our data revealed that chlorogenic acid had significant lowering effect on the inflammatory response. Treatment with chlorogenic acid (25-50 μM) significantly decreased gene expression and concentration of proinflammatory cytokines IL-6 and IL-8 compared to LPS-treated cells. COX-2 and TNF-α mRNA levels were also reduced. Furthermore, chlorogenic acid reduced the level of reactive oxygen species in IPEC-J2 cells. Simultaneous application of chlorogenic acid and Lactobacillus plantarum 2142 supernatant resulted protective effect against LPS-induced inflammation and oxidative stress as well.

  2. Inhibition of Epithelial TNF-α Receptors by Purified Fruit Bromelain Ameliorates Intestinal Inflammation and Barrier Dysfunction in Colitis

    OpenAIRE

    Zhou, Zijuan; Wang, Liang; Feng, Panpan; Yin, Lianhong; Wang, Chen; Zhi, Shengxu; Dong, Jianyi; Wang, Jingyu; Lin, Yuan; Chen, Dapeng; Xiong, Yongjian; Peng, Jinyong

    2017-01-01

    Activation of the TNF-α receptor (TNFR) leads to an inflammatory response, and anti-TNF therapy has been administered to reduce inflammation symptoms and heal mucosal ulcers in inflammatory bowel disease (IBD). Bromelain, a complex natural mixture of proteolytic enzymes, has been shown to exert anti-inflammatory effects. This study aimed to investigate the effect of purified fruit bromelain (PFB)-induced inhibition of epithelial TNFR in a rat colitis model. Colitis was established by intracol...

  3. Is butyrate the link between diet, intestinal microbiota and obesity-related metabolic diseases?

    Science.gov (United States)

    Brahe, L K; Astrup, A; Larsen, L H

    2013-12-01

    It is increasingly recognized that there is a connection between diet, intestinal microbiota, intestinal barrier function and the low-grade inflammation that characterizes the progression from obesity to metabolic disturbances, making dietary strategies to modulate the intestinal environment relevant. In this context, the ability of some Gram-positive anaerobic bacteria to produce the short-chain fatty acid butyrate is interesting. A lower abundance of butyrate-producing bacteria has been associated with metabolic risk in humans, and recent studies suggest that butyrate might have an anti-inflammatory potential that can alleviate obesity-related metabolic complications, possibly due to its ability to enhance the intestinal barrier function. Here, we review and discuss the potential of butyrate as an anti-inflammatory mediator in metabolic diseases, and the potential for dietary interventions increasing the intestinal availability of butyrate. © 2013 The Authors. obesity reviews © 2013 International Association for the Study of Obesity.

  4. Oral treatment with herbal formula B307 alleviates cardiac failure in aging R6/2 mice with Huntington’s disease via suppressing oxidative stress, inflammation, and apoptosis

    Directory of Open Access Journals (Sweden)

    Lin CL

    2015-07-01

    reduced under oral B307 treatment (P<0.05. Oral B307 treatment may briefly alleviate cardiac failure in aging HD R6/2 mice via suppressing cardiac oxidative stress, inflammation, and apoptosis. We suggested that the herbal formula B307 may be further developed as a potential health supplement for ameliorating cardiac failure associated with aging. Keywords: Chinese herbal medicines, cardiomyocytes, echocardiography, aging, transgenic mouse model

  5. Selective non-steroidal glucocorticoid receptor agonists attenuate inflammation but do not impair intestinal epithelial cell restitution in vitro.

    Directory of Open Access Journals (Sweden)

    Kerstin C Reuter

    Full Text Available INTRODUCTION: Despite the excellent anti-inflammatory and immunosuppressive action of glucocorticoids (GCs, their use for the treatment of inflammatory bowel disease (IBD still carries significant risks in terms of frequently occurring severe side effects, such as the impairment of intestinal tissue repair. The recently-introduced selective glucocorticoid receptor (GR agonists (SEGRAs offer anti-inflammatory action comparable to that of common GCs, but with a reduced side effect profile. METHODS: The in vitro effects of the non-steroidal SEGRAs Compound A (CpdA and ZK216348, were investigated in intestinal epithelial cells and compared to those of Dexamethasone (Dex. GR translocation was shown by immunfluorescence and Western blot analysis. Trans-repressive effects were studied by means of NF-κB/p65 activity and IL-8 levels, trans-activation potency by reporter gene assay. Flow cytometry was used to assess apoptosis of cells exposed to SEGRAs. The effects on IEC-6 and HaCaT cell restitution were determined using an in vitro wound healing model, cell proliferation by BrdU assay. In addition, influences on the TGF-β- or EGF/ERK1/2/MAPK-pathway were evaluated by reporter gene assay, Western blot and qPCR analysis. RESULTS: Dex, CpdA and ZK216348 were found to be functional GR agonists. In terms of trans-repression, CpdA and ZK216348 effectively inhibited NF-κB activity and IL-8 secretion, but showed less trans-activation potency. Furthermore, unlike SEGRAs, Dex caused a dose-dependent inhibition of cell restitution with no effect on cell proliferation. These differences in epithelial restitution were TGF-β-independent but Dex inhibited the EGF/ERK1/2/MAPK-pathway important for intestinal epithelial wound healing by induction of MKP-1 and Annexin-1 which was not affected by CpdA or ZK216348. CONCLUSION: Collectively, our results indicate that, while their anti-inflammatory activity is comparable to Dex, SEGRAs show fewer side effects with

  6. The effect of bovine colostrum products on intestinal dysfunction and inflammation in a preterm pig model of necrotizing enterocolitis

    DEFF Research Database (Denmark)

    Støy, Ann Cathrine Findal

    and spray dried BC. The study showed that even though spray drying and pasteurization affected BC proteins, pasteurized and/or spray dried BC decreased the severity of NEC in pigs compared with milk formula, while a tendency towards lower NEC severity was observed in pig fed raw BC compared with milk......Necrotizing enterocolitis (NEC), primarily seen in preterm infants, is associated with high morbidity and mortality. The pathogenesis is not fully understood but risk factors include prematurity, enteral feeding (especially with milk formula), and the intestinal microbiota. Mother’s milk, rich...... in bioactive factors, has a protective effect against NEC, but not all preterm infants are able to receive mother’s milk. The overall aim of this thesis was to investigate if bovine colostrum (BC), also rich in bioactive factors, could serve as an alternative to mother’s milk. A preterm pig model of NEC...

  7. Effect of lidocaine on inflammation in equine jejunum subjected to manipulation only and remote to intestinal segments subjected to ischemia.

    Science.gov (United States)

    Bauck, Anje G; Grosche, Astrid; Morton, Alison J; Graham, A Sarah; Vickroy, Thomas W; Freeman, David E

    2017-08-01

    OBJECTIVE To examine effects of continuous rate infusion of lidocaine on transmural neutrophil infiltration in equine intestine subjected to manipulation only and remote to ischemic intestine. ANIMALS 14 healthy horses. PROCEDURES Ventral midline celiotomy was performed (time 0). Mild ischemia was induced in segments of jejunum and large colon. A 1-m segment of jejunum was manipulated by massaging the jejunal wall 10 times. Horses received lidocaine (n = 7) or saline (0.9% NaCl) solution (7) throughout anesthesia. Biopsy specimens were collected and used to assess tissue injury, neutrophil influx, cyclooxygenase expression, and hypoxia-inducible factor 1α (HIF-1α) expression at 0, 1, and 4 hours after manipulation and ischemia. Transepithelial resistance (TER) and mannitol flux were measured by use of Ussing chambers. RESULTS Lidocaine did not consistently decrease neutrophil infiltration in ischemic, manipulated, or control tissues at 4 hours. Lidocaine significantly reduced circular muscle and overall scores for cyclooxygenase-2 expression in manipulated tissues. Manipulated tissues had significantly less HIF-1α expression at 4 hours than did control tissues. Mucosa from manipulated and control segments obtained at 4 hours had lower TER and greater mannitol flux than did control tissues at 0 hours. Lidocaine did not significantly decrease calprotectin expression. Severity of neutrophil infiltration was similar in control, ischemic, and manipulated tissues at 4 hours. CONCLUSIONS AND CLINICAL RELEVANCE Manipulated jejunum did not have a significantly greater increase in neutrophil infiltration, compared with 4-hour control (nonmanipulated) jejunum remote to sites of manipulation, ischemia, and reperfusion. Lidocaine did not consistently reduce neutrophil infiltration in jejunum.

  8. Immunization with Bacillus Calmette-Guérin (BCG) alleviates neuroinflammation and cognitive deficits in APP/PS1 mice via the recruitment of inflammation-resolving monocytes to the brain.

    Science.gov (United States)

    Zuo, Zejie; Qi, Fangfang; Yang, Junhua; Wang, Xiao; Wu, Yingying; Wen, Yaru; Yuan, Qunfang; Zou, Juntao; Guo, Kaihua; Yao, Zhi Bin

    2017-05-01

    The immune system plays a crucial role in the progression of Alzheimer's disease (AD). Recently, immune-dependent cascade induced by systemic immune activation has been verified to play a beneficial role in AD mouse models. Here, we tested whether Bacillus Calmette-Guérin (BCG) immunization alters AD pathology and cognitive dysfunction in APP/PS1 AD mouse model, and with 4Aβ1-15 vaccination as positive control. It was found that BCG treatment reversed the cognitive decline to the extent observed in 4Aβ1-15 group, but did not reduce the β-amyloid (Aβ) burden in the brain. Then, we demonstrated the enhanced recruitment of inflammation-resolving monocytes across the choroid plexus and perivascular spaces to cerebral sites of plaque pathology in APP/PS1 mice immunized with BCG. Furthermore, elevated splenocyte Foxp3 + regulatory T cell levels in the control APP/PS1 mice were down-regulated back to the wild-type (WT) levels by BCG treatment but not 4Aβ1-15 vaccination. In addition, BCG treatment induced the production of more circulating interferon (IFN)-γ than the controls and 4Aβ1-15 vaccination. Though the similar reductions in brain levels of pro-inflammatory cytokines were observed in the BCG and 4Aβ1-15 groups compared to the controls, only BCG had the great effect in upregulating cerebral anti-inflammatory cytokine levels as well as elevating the expression of neurotrophic factors in the brain of APP/PS1 mice. Thus, it is suggested that BCG exerts a beneficial immunomodulatory effect in APP/PS1 mice through mitigation of systemic immune suppression, induction of IFN-γ response and alleviation of the neuroinflammatory response. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Effect of the smell of Seirogan, a wood creosote, on dermal and intestinal mucosal immunity and allergic inflammation

    Science.gov (United States)

    Hiramoto, Keiichi; Yamate, Yurika; Kobayashi, Hiromi; Ishii, Masamitsu; Miura, Takanori; Sato, Eisuke F.; Inoue, Masayasu

    2012-01-01

    Seirogan, a wood creosote, has been used as an antidiarrhetic drug in Asian countries including Japan for many years. This antidiarrhetic has recently been used as a sugar-coated pill because Seirogan has a strong smell. The strong smell of the uncoated form of Seirogan may modulate the defense systems of animals because the sense of smell is important for the detection of toxic metabolites in foods contaminated with pathogens. This study examined the effect of the sugar-coated and uncoated forms of this antidiarrhetic on the immunological response and inflammatory reactions in mice that had been sensitized with either fluorescein isothiocyanate or oxazolone. The sensitization of mice with either FITC or oxazolone markedly increased the plasma levels of tumor necrosis factor-α and mucosal IgA and elicited severe inflammation in the colon by a mechanism that could be suppressed by exposure of animals to the smell of uncoated Seirogan as effectively as the oral administration of the agent. Dermal inflammation in the FITC- and oxazolone-sensitized mice was also suppressed effectively either by the exposure to the smell or oral administration of the agent. Biochemical and histochemical analyses revealed that the elevated levels of plasma tumor necrosis factor-α and mucosal IgA were significantly decreased by exposure to the smell of uncoated Seirogan as well as by oral administration of the agent. Exposure of mice to the smell of Seirogan but not oral administration of the agent selectively increased plasma levels of adrenocorticotropic hormone and cortisol, particularly in the sensitized animals. These observations suggest that exposing the animals to the smell of Seirogan per se activated the hypothalamo-pituitary-adrenal axis and systemically modulated immunological reactions to suppress the allergic reactions. PMID:22962524

  10. Efficacy of oral administration of heat-killed probiotics from Mongolian dairy products against influenza infection in mice: alleviation of influenza infection by its immunomodulatory activity through intestinal immunity.

    Science.gov (United States)

    Takeda, Shiro; Takeshita, Masahiko; Kikuchi, Yukiharu; Dashnyam, Bumbein; Kawahara, Satoshi; Yoshida, Hiroki; Watanabe, Wataru; Muguruma, Michio; Kurokawa, Masahiko

    2011-12-01

    Some probiotics possess immunomodulatory activities and have been used as complementary and alternative medicines. We previously found that 10 lactic acid bacteria (LAB) strains isolated from traditional Mongolian dairy products showed probiotic potential in vitro. In this study, we assessed the immunomodulatory activity of 10 LABs on influenza virus (IFV) infection in relation to their efficacies in IFV-infected mice. In an intranasal IFV infection model in mice, oral administration of boiled Lactobacillus plantarum 06CC2 strain (20mg/mouse), one of the 10 LABs, twice daily for 10 days starting two days before infection was significantly effective in protecting the body weight loss of infected mice, reducing virus yields in the lungs on days 2, 4, and 6 after infection, and prolonging survival times without toxicity. The total numbers of infiltrated cells in the bronchoalveolar lavage fluid (BALF), especially macrophages and neutrophils, were significantly reduced by 06CC2 administration on day 2. On day 2, tumor necrosis factor (TNF)-α production in BALF was also reduced significantly, but interferon-α, interleukin-12, and interferon-γ productions were augmented and natural killer (NK) cell activity was significantly elevated. Furthermore, the gene expressions of interleukin-12 receptor and interferon-γ in Peyer's patches were augmented by 06CC2 administration on day 2. Thus, 06CC2 was suggested to alleviate influenza symptoms in mice in correlation with the augmentation of NK cell activity associated with the enhancement of interferon-α and Th1 cytokine productions through intestinal immunity and the reduction of TNF-α in the early stage of infection. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. Novel hydroquinone derivatives alleviate algesia, inflammation and ...

    African Journals Online (AJOL)

    ulcerogenicity using well- known testing ... Non-steroidal anti-inflammatory drugs (NSAIDs) .... Animals. BALB/c mice and Sprague–Dawley rats of either sex were used and housed separately as 6 animals per cage, under laboratory conditions of.

  12. Novel hydroquinone derivatives alleviate algesia, inflammation and ...

    African Journals Online (AJOL)

    The in silico studies predicted high binding affinity of the hydroquinone derivatives to the active site of the cyclooxygenase 2 (COX-2) enzyme. Conclusion: The synthesized hydroquinone compounds possess analgesic, antipyretic and antiinflammatory properties with low gastric-ulcerogenic potential. This may be credited to ...

  13. Crotoxin from Crotalus durissus terrificus is able to down-modulate the acute intestinal inflammation in mice.

    Directory of Open Access Journals (Sweden)

    Caroline de Souza Almeida

    Full Text Available Inflammatory bowel diseases (IBD is the result of dysregulation of mucosal innate and adaptive immune responses. Factors such as genetic, microbial and environmental are involved in the development of these disorders. Accordingly, animal models that mimic human diseases are tools for the understanding the immunological processes of the IBD as well as to evaluate new therapeutic strategies. Crotoxin (CTX is the main component of Crotalus durissus terrificus snake venom and has an immunomodulatory effect. Thus, we aimed to evaluate the modulatory effect of CTX in a murine model of colitis induced by 2,4,6- trinitrobenzene sulfonic acid (TNBS. The CTX was administered intraperitoneally 18 hours after the TNBS intrarectal instillation in BALB/c mice. The CTX administration resulted in decreased weight loss, disease activity index (DAI, macroscopic tissue damage, histopathological score and myeloperoxidase (MPO activity analyzed after 4 days of acute TNBS colitis. Furthermore, the levels of TNF-α, IL-1β and IL-6 were lower in colon tissue homogenates of TNBS-mice that received the CTX when compared with untreated TNBS mice. The analysis of distinct cell populations obtained from the intestinal lamina propria showed that CTX reduced the number of group 3 innate lymphoid cells (ILC3 and Th17 population; CTX decreased IL-17 secretion but did not alter the frequency of CD4+Tbet+ T cells induced by TNBS instillation in mice. In contrast, increased CD4+FoxP3+ cell population as well as secretion of TGF-β, prostaglandin E2 (PGE2 and lipoxin A4 (LXA4 was observed in TNBS-colitis mice treated with CTX compared with untreated TNBS-colitis mice. In conclusion, the CTX is able to modulate the intestinal acute inflammatory response induced by TNBS, resulting in the improvement of clinical status of the mice. This effect of CTX is complex and involves the suppression of the pro-inflammatory environment elicited by intrarectal instillation of TNBS due to the

  14. Unraveling the ties between irritable bowel syndrome and intestinal microbiota.

    Science.gov (United States)

    Hong, Sung Noh; Rhee, Poong-Lyul

    2014-03-14

    Irritable bowel syndrome (IBS) is the most prevalent functional gastrointestinal disorder. It is a multifactorial disorder. Intestinal microbiota may cause the pathogenesis of IBS by contributing to abnormal gastrointestinal motility, low-grade inflammation, visceral hypersensitivity, communication in the gut-brain axis, and so on. Previous attempts to identify the intestinal microbiota composition in IBS patients have yielded inconsistent and occasionally contradictory results. This inconsistency may be due to the differences in the molecular techniques employed, the sample collection and handling methods, use of single samples that are not linked to fluctuating symptoms, or other factors such as patients' diets and phenotypic characterizations. Despite these difficulties, previous studies found that the intestinal microbiota in some IBS patients was completely different from that in healthy controls, and there does appear to be a consistent theme of Firmicutes enrichment and reduced abundance of Bacteroides. Based on the differences in intestinal microbiota composition, many studies have addressed the roles of microbiota-targeted treatments, such as antibiotics and probiotics, in alleviating certain symptoms of IBS. This review summarizes the current knowledge of the associations between intestinal microbiota and IBS as well as the possible modes of action of intestinal microbiota in the pathogenesis of IBS. Improving the current level of understanding of host-microbiota interactions in IBS is important not only for determining the role of intestinal microbiota in IBS pathogenesis but also for therapeutic modulation of the microbiota.

  15. Loss of ileum decreases serum fibroblast growth factor 19 in relation to liver inflammation and fibrosis in pediatric onset intestinal failure.

    Science.gov (United States)

    Mutanen, Annika; Lohi, Jouko; Heikkilä, Päivi; Jalanko, Hannu; Pakarinen, Mikko P

    2015-06-01

    The pathogenesis of intestinal failure (IF) associated liver disease (IFALD) is uncertain, we therefore investigated the role of FGF19 and pro-inflammatory cytokines has on this disease state. Serum FGF19, IL-6 and, TNF-α were measured in 52 IF patients at median age 6.0 years (IQR 2.2-13) after 10 months (4.1-39) on parenteral nutrition (PN). Thirty-nine patients underwent liver biopsies. In IF patients, FGF19 concentrations were lower and those of IL-6 and TNF-α higher compared to healthy matched controls (p ⩽ 0.001 for all). FGF19 concentrations were further decreased in patients without a remaining ileum [37 pg/ml (IQR 30-68) vs. 74 (35-135) p=0.028], and correlated with remaining ileum length (r = 0.333, p = 0.018) and markers of cholesterol synthesis (r = -0.552 to -0.643, p pediatric onset of IF, total or partial loss of ileum decreases serum FGF19 concentration corresponding to hepatic inflammation and fibrosis, along with increased cholesterol synthesis. In contrast, serum IL-6 increases during PN and may associate with concurrent cholestasis. These data suggests that FGF19 may contribute to the pathogenesis of IFALD. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  16. The Anti-Inflammatory Effect and Intestinal Barrier Protection of HU210 Differentially Depend on TLR4 Signaling in Dextran Sulfate Sodium-Induced Murine Colitis.

    Science.gov (United States)

    Lin, Sisi; Li, Yongyu; Shen, Li; Zhang, Ruiqin; Yang, Lizhi; Li, Min; Li, Kun; Fichna, Jakub

    2017-02-01

    Ulcerative colitis (UC) is strongly associated with inflammation and intestinal barrier disorder. The nonselective cannabinoid receptor agonist HU210 has been shown to ameliorate inflamed colon in colitis, but its effects on intestinal barrier function and extraintestinal inflammation are unclear. To investigate the effects and the underlying mechanism of HU210 action on the UC in relation to a role of TLR4 and MAP kinase signaling. Wild-type (WT) and TLR4 knockout (Tlr4 -/- ) mice were exposed to 4% dextran sulfate sodium (DSS) for 7 days. The effects of HU210 on inflammation and intestinal barrier were explored. Upon DSS challenge, mice suffered from bloody stool, colon shortening, intestinal mucosa edema, pro-inflammatory cytokine increase and intestinal barrier destruction with goblet cell depletion, increased intestinal microflora accompanied with elevated plasma lipopolysaccharide, reduced mRNA expression of the intestinal tight junction proteins, and abnormal ratio of CD4 + /CD8 + T cells in the intestinal Peyer's patches. Pro-inflammatory cytokines in the plasma and the lung, as well as pulmonary myeloperoxidase activity, indicators of extraintestinal inflammation were increased. Protein expression of p38α and pp38 was up-regulated in the colon of WT mice. Tlr4 -/- mice showed milder colitis. HU210 reversed the intestinal barrier changes in both strains of mice, but alleviated inflammation only in WT mice. Our study indicates that in experimental colitis, HU210 displays a protective effect on the intestinal barrier function independently of the TLR4 signaling pathway; however, in the extraintestinal tissues, the anti-inflammatory action seems through affecting TLR4-mediated p38 mitogen-activated protein kinase pathway.

  17. Gastric and intestinal surgery.

    Science.gov (United States)

    Fossum, Theresa W; Hedlund, Cheryl S

    2003-09-01

    Gastric surgery is commonly performed to remove foreign bodies and correct gastric dilatation-volvulus and is less commonly performed to treat gastric ulceration or erosion, neoplasia, and benign gastric outflow obstruction. Intestinal surgery, although commonly performed by veterinarians, should never be considered routine. The most common procedures of the small intestinal tract performed in dogs and cats include enterotomy and resection/anastomosis. Surgery of the large intestine is indicated for lesions causing obstruction, perforations, colonic inertia, or chronic inflammation.

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

    DEFF Research Database (Denmark)

    Holmkvist, Petra; Pool, Lieneke; Hägerbrand, Karin

    2016-01-01

    IL-18 has been implicated in inflammatory bowel disease (IBD), however its role in the regulation of intestinal CD4+ T-cell function remains unclear. Here we show that murine intestinal CD4+ T cells express high levels of IL-18Rα and provide evidence that IL-18Rα expression is induced on these ce......IL-18 has been implicated in inflammatory bowel disease (IBD), however its role in the regulation of intestinal CD4+ T-cell function remains unclear. Here we show that murine intestinal CD4+ T cells express high levels of IL-18Rα and provide evidence that IL-18Rα expression is induced...

  19. Farnesoid X Receptor Activation Attenuates Intestinal Ischemia Reperfusion Injury in Rats.

    Directory of Open Access Journals (Sweden)

    Laurens J Ceulemans

    Full Text Available The farnesoid X receptor (FXR is abundantly expressed in the ileum, where it exerts an enteroprotective role as a key regulator of intestinal innate immunity and homeostasis, as shown in pre-clinical models of inflammatory bowel disease. Since intestinal ischemia reperfusion injury (IRI is characterized by hyperpermeability, bacterial translocation and inflammation, we aimed to investigate, for the first time, if the FXR-agonist obeticholic acid (OCA could attenuate intestinal ischemia reperfusion injury.In a validated rat model of intestinal IRI (laparotomy + temporary mesenteric artery clamping, 3 conditions were tested (n = 16/group: laparotomy only (sham group; ischemia 60min+ reperfusion 60min + vehicle pretreatment (IR group; ischemia 60min + reperfusion 60min + OCA pretreatment (IR+OCA group. Vehicle or OCA (INT-747, 2*30mg/kg was administered by gavage 24h and 4h prior to IRI. The following end-points were analyzed: 7-day survival; biomarkers of enterocyte viability (L-lactate, I-FABP; histology (morphologic injury to villi/crypts and villus length; intestinal permeability (Ussing chamber; endotoxin translocation (Lipopolysaccharide assay; cytokines (IL-6, IL-1-β, TNFα, IFN-γ IL-10, IL-13; apoptosis (cleaved caspase-3; and autophagy (LC3, p62.It was found that intestinal IRI was associated with high mortality (90%; loss of intestinal integrity (structurally and functionally; increased endotoxin translocation and pro-inflammatory cytokine production; and inhibition of autophagy. Conversely, OCA-pretreatment improved 7-day survival up to 50% which was associated with prevention of epithelial injury, preserved intestinal architecture and permeability. Additionally, FXR-agonism led to decreased pro-inflammatory cytokine release and alleviated autophagy inhibition.Pretreatment with OCA, an FXR-agonist, improves survival in a rodent model of intestinal IRI, preserves the gut barrier function and suppresses inflammation. These results turn

  20. Probiotic supplementation affects markers of intestinal barrier, oxidation, and inflammation in trained men; a randomized, double-blinded, placebo-controlled trial

    Directory of Open Access Journals (Sweden)

    Lamprecht Manfred

    2012-09-01

    Full Text Available Abstract Background Probiotics are an upcoming group of nutraceuticals claiming positive effects on athlete’s gut health, redox biology and immunity but there is lack of evidence to support these statements. Methods We conducted a randomized, double-blinded, placebo controlled trial to observe effects of probiotic supplementation on markers of intestinal barrier, oxidation and inflammation, at rest and after intense exercise. 23 trained men received multi-species probiotics (1010 CFU/day, Ecologic®Performance or OMNi-BiOTiC®POWER, n = 11 or placebo (n = 12 for 14 weeks and performed an intense cycle ergometry over 90 minutes at baseline and after 14 weeks. Zonulin and α1-antitrypsin were measured from feces to estimate gut leakage at baseline and at the end of treatment. Venous blood was collected at baseline and after 14 weeks, before and immediately post exercise, to determine carbonyl proteins (CP, malondialdehyde (MDA, total oxidation status of lipids (TOS, tumor necrosis factor-alpha (TNF-α, and interleukin-6 (IL-6. Statistical analysis used multifactorial analysis of variance (ANOVA. Level of significance was set at p  Results Zonulin decreased with supplementation from values slightly above normal into normal ranges ( 0.1. CP increased significantly from pre to post exercise in both groups at baseline and in the placebo group after 14 weeks of treatment (p = 0.006. After 14 weeks, CP concentrations were tendentially lower with probiotics (p = 0.061. TOS was slightly increased above normal in both groups, at baseline and after 14 weeks of treatment. There was no effect of supplementation or exercise on TOS. At baseline, both groups showed considerably higher TNF-α concentrations than normal. After 14 weeks TNF-α was tendentially lower in the supplemented group (p = 0.054. IL-6 increased significantly from pre to post exercise in both groups (p = 0.001, but supplementation had no effect. MDA

  1. Effect of monocolonization with Escherichia coli stranis 06K13 and Nissle 1917 on the development of experimentally induced acute and chronic intestinal inflammation in germ-free immunocompetent and immunodeficient mice

    Czech Academy of Sciences Publication Activity Database

    Hudcovic, Tomáš; Štěpánková, Renata; Kozáková, Hana; Hrnčíř, Tomáš; Tlaskalová, Helena

    2007-01-01

    Roč. 52, č. 6 (2007), s. 618-626 ISSN 0015-5632 R&D Projects: GA ČR GA303/04/0849; GA ČR GA303/06/0974; GA AV ČR 1QS500200572; GA MŠk 2B06155; GA MŠk 2B06053 Institutional research plan: CEZ:AV0Z50200510 Keywords : escherichia coli * intestinal inflammation * nissle 1917 Subject RIV: EC - Immunology Impact factor: 0.989, year: 2007

  2. Pediatric intestinal failure-associated liver disease.

    Science.gov (United States)

    Courtney, Cathleen M; Warner, Brad W

    2017-06-01

    The goal of this review is to provide updates on the definition, pathophysiology, treatment, and prevention of intestinal failure-associated liver disease (IFALD) that are relevant to care of pediatric patients. Current literature emphasizes the multifactorial nature of IFALD. The pathogenesis is still largely unknown; however, molecular pathways have been identified. Key to these pathways are proinflammatory cytokines involved in hepatic inflammation and bile acids synthesis such as Toll-like receptor 4 and farnesoid X receptor, respectively. Research for prevention and treatment is aimed at alleviating risk factors associated with IFALD, principally those associated with parental nutrition. Multiple nutrients and amino acids are relevant to the development of IFALD, but lipid composition has been the primary focus. Lipid emulsions with a lower ratio of omega-6-to-omega-3 polyunsaturated fatty acids (FAs) appear to improve bile flow and decrease intrahepatic inflammation. Long-term consequences of these alternative lipid emulsions are yet to be determined. IFALD remains the greatest contributor of mortality in patients with intestinal failure. Many factors contribute to its development, namely, alterations in the gut microbiome, sepsis, and lack of enteral intake. Novel combinations of lipid formulations are promising alternatives to purely soy-based formulas to reduce cholestasis.

  3. Sustained TL1A (TNFSF15) expression on both lymphoid and myeloid cells leads to mild spontaneous intestinal inflammation and fibrosis

    OpenAIRE

    Zheng, Libo; Zhang, Xiaolan; Chen, Jeremy; Ichikawa, Ryan; Wallace, Kori; Pothoulakis, Charalabos; Koon, Hon Wai; Targan, Stephan R.; Shih, David Q.

    2013-01-01

    TL1A is a member of the TNF superfamily, and its expression is increased in the mucosa of inflammatory bowel disease patients. Moreover, patients with certain TNFSF15 variants over-express TL1A and have a higher risk of developing strictures in the small intestine. Consistently, mice with sustained Tl1a expression in either lymphoid or myeloid cells develop spontaneous ileitis and increased intestinal collagen deposition. Transgenic (Tg) mice with constitutive Tl1a expressio...

  4. Modulation of inflammatory mediators by Opuntia ficus-indica and Prunus avium bioproducts using an in vitro cell-based model of intestinal inflammation

    OpenAIRE

    Nunes, Sara Alexandra Luis

    2011-01-01

    Dissertation to obtain a Master Degree in Biotechnology Inflammatory Bowel Diseases, namely Ulcerative colitis and Crohn’s disease, are chronic intestinal inflammatory disorders characterized by an excessive release of pro-inflammatory mediators, intestinal barrier dysfunction and altered permeability and excessive activation of NF-κB cascade that can lead to development of colon cancer. IBD conventional therapy involves multiple medications and long-term up to life-long treatments. Furthe...

  5. Flaxseed Oil Attenuates Intestinal Damage and Inflammation by Regulating Necroptosis and TLR4/NOD Signaling Pathways Following Lipopolysaccharide Challenge in a Piglet Model.

    Science.gov (United States)

    Zhu, Huiling; Wang, Haibo; Wang, Shuhui; Tu, Zhixiao; Zhang, Lin; Wang, Xiuying; Hou, Yongqing; Wang, Chunwei; Chen, Jie; Liu, Yulan

    2018-03-06

    Flaxseed oil is a rich source of α-linolenic acid (ALA), which is the precursor of the long-chain n-3 polyunsaturated fatty acids (PUFAs) including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). This study investigated the protective effect of flaxseed oil against intestinal injury induced by lipopolysaccharide (LPS). Twenty-four weaned pigs were used in a 2 × 2 factorial experiment with dietary treatment (5% corn oil vs. 5% flaxseed oil) and LPS challenge (saline vs. LPS). On d 21 of the experiment, pigs were administrated with LPS or saline. At 2 and 4 h post-administration, blood samples were collected. After the blood harvest at 4 h, all piglets were slaughtered and intestinal samples were collected. Flaxseed oil supplementation led to the enrichment of ALA, EPA and total n-3 PUFAs in intestine. Flaxseed oil improved intestinal morphology, jejunal lactase activity and claudin-1 protein expression. Flaxseed oil downregulated the mRNA expression of intestinal necroptotic signals. Flaxseed oil also downregulated the mRNA expression of intestinal toll-like receptors 4 (TLR4) and its downstream signals myeloid differentiation factor 88 (MyD88), nuclear factor kappa B (NFκB), and nucleotide-binding oligomerization domain proteins 1, 2 (NOD1, NOD2) and its adaptor molecule, receptor interacting protein kinases 2 (RIPK2). These results suggest that dietary addition of flaxseed oil enhances intestinal integrity and barrier function, which is involved in modulating necroptosis and TLR4/NOD signaling pathways. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  6. Effects of sodium hydrosulfide on intestinal mucosal injury in a rat model of cardiac arrest and cardiopulmonary resuscitation.

    Science.gov (United States)

    Pan, Hao; Chen, Di; Liu, Beibei; Xie, Xuemeng; Zhang, Jincheng; Yang, Guangtian

    2013-07-19

    Cardiac arrest and cardiopulmonary resuscitation (CPR) can lead to intestinal ischemia/reperfusion (I/R) injury. Increasing studies have indicated that hydrogen sulfide (H2S) is in favor of a variety of tissue I/R injury. The purpose of this study was to explore whether sodium hydrosulfide (NaHS), a H2S donor, can protect intestinal mucosa after CPR and its potential mechanisms. Male Sprague-Dawley rats were subjected to 6min cardiac arrest induced by transcutaneous electrical epicardium stimulation and then resuscitated successfully. A bolus of either NaHS (0.5mg/kg) or placebo (NaCl 0.9%) was blindly injected 1min before the start of CPR intravenously, followed by a continuous injection of NaHS (2mg/kg/h) or placebo for 3h. Intestinal and plasma samples were collected for assessments 24h after CPR. We found that NaHS can markedly alleviate cardiac arrest induced intestinal mucosal injury. Rats treated with NaHS showed a lower malondialdehyde content, higher superoxide dismutase activity and glutathione content in intestine after CPR. Increased intestinal myeloperoxidase activity was significantly decreased by NaHS after CPR. Moreover, a reduced intestinal apoptotic cells after CPR were evident when pretreated with NaHS. Further studies indicated that NaHS enhances the expression of hypoxia-inducible factor-1α (HIF-1α) in intestine after CPR. Our data demonstrated that NaHS treatment before CPR induces intestinal mucosal protection 24h post-resuscitation. The protective effects may be through oxidative stress reduction, inflammation alleviation, apoptosis inhibition and HIF-1α activation. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Opposite effect of oxidative stress on inducible nitric oxide synthase and haem oxygenase-1 expression in intestinal inflammation: anti-inflammatory effect of carbon monoxide

    NARCIS (Netherlands)

    Dijkstra, Gerard; Blokzijl, Hans; Bok, Lisette; Homan, Manon; van Goor, Harry; Faber, Klaas Nico; Jansen, Peter L. M.; Moshage, Han

    2004-01-01

    Inducible nitric oxide synthase (iNOS) is expressed in intestinal epithelial cells (IEC) of patients with active inflammatory bowel disease (IBD) and in IEC of endotoxaemic rats. The induction of iNOS in IEC is an element of the NF-kappaB-mediated survival pathway. Haem oxygenase-1 (HO-1) is an

  8. Intestinal microbiota and ulcerative colitis.

    Science.gov (United States)

    Ohkusa, Toshifumi; Koido, Shigeo

    2015-11-01

    There is a close relationship between the human host and the intestinal microbiota, which is an assortment of microorganisms, protecting the intestine against colonization by exogenous pathogens. Moreover, the intestinal microbiota play a critical role in providing nutrition and the modulation of host immune homeostasis. Recent reports indicate that some strains of intestinal bacteria are responsible for intestinal ulceration and chronic inflammation in inflammatory bowel diseases (IBD) such as ulcerative colitis (UC) and Crohn's disease (CD). Understanding the interaction of the intestinal microbiota with pathogens and the human host might provide new strategies treating patients with IBD. This review focuses on the important role that the intestinal microbiota plays in maintaining innate immunity in the pathogenesis and etiology of UC and discusses new antibiotic therapies targeting the intestinal microbiota. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  9. Cell walls of Saccharomyces cerevisiae differentially modulated innate immunity and glucose metabolism during late systemic inflammation.

    Directory of Open Access Journals (Sweden)

    Bushansingh Baurhoo

    Full Text Available BACKGROUND: Salmonella causes acute systemic inflammation by using its virulence factors to invade the intestinal epithelium. But, prolonged inflammation may provoke severe body catabolism and immunological diseases. Salmonella has become more life-threatening due to emergence of multiple-antibiotic resistant strains. Mannose-rich oligosaccharides (MOS from cells walls of Saccharomyces cerevisiae have shown to bind mannose-specific lectin of Gram-negative bacteria including Salmonella, and prevent their adherence to intestinal epithelial cells. However, whether MOS may potentially mitigate systemic inflammation is not investigated yet. Moreover, molecular events underlying innate immune responses and metabolic activities during late inflammation, in presence or absence of MOS, are unknown. METHODS AND PRINCIPAL FINDINGS: Using a Salmonella LPS-induced systemic inflammation chicken model and microarray analysis, we investigated the effects of MOS and virginiamycin (VIRG, a sub-therapeutic antibiotic on innate immunity and glucose metabolism during late inflammation. Here, we demonstrate that MOS and VIRG modulated innate immunity and metabolic genes differently. Innate immune responses were principally mediated by intestinal IL-3, but not TNF-α, IL-1 or IL-6, whereas glucose mobilization occurred through intestinal gluconeogenesis only. MOS inherently induced IL-3 expression in control hosts. Consequent to LPS challenge, IL-3 induction in VIRG hosts but not differentially expressed in MOS hosts revealed that MOS counteracted LPS's detrimental inflammatory effects. Metabolic pathways are built to elucidate the mechanisms by which VIRG host's higher energy requirements were met: including gene up-regulations for intestinal gluconeogenesis (PEPCK and liver glycolysis (ENO2, and intriguingly liver fatty acid synthesis through ATP citrate synthase (CS down-regulation and ATP citrate lyase (ACLY and malic enzyme (ME up-regulations. However, MOS host

  10. Effects of propofol on damage of rat intestinal epithelial cells induced by heat stress and lipopolysaccharides

    Energy Technology Data Exchange (ETDEWEB)

    Tang, J.; Jiang, Y. [Southern Medical University, Nanfang Hospital, Department of Anesthesia, Guangzhou, China, Department of Anesthesia, Nanfang Hospital, Southern Medical University, Guangzhou (China); Tang, Y.; Chen, B. [Guangzhou General Hospital of Guangzhou Military Command, Department of Intensive Care Unit, Guangzhou, China, Department of Intensive Care Unit, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou (China); Sun, X. [Laboratory of Traditional Chinese Medicine Syndrome, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou (China); Su, L.; Liu, Z. [Guangzhou General Hospital of Guangzhou Military Command, Department of Intensive Care Unit, Guangzhou, China, Department of Intensive Care Unit, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou (China)

    2013-06-25

    Gut-derived endotoxin and pathogenic bacteria have been proposed as important causative factors of morbidity and death during heat stroke. However, it is still unclear what kind of damage is induced by heat stress. In this study, the rat intestinal epithelial cell line (IEC-6) was treated with heat stress or a combination of heat stress and lipopolysaccharide (LPS). In addition, propofol, which plays an important role in anti-inflammation and organ protection, was applied to study its effects on cellular viability and apoptosis. Heat stress, LPS, or heat stress combined with LPS stimulation can all cause intestinal epithelial cell damage, including early apoptosis and subsequent necrosis. However, propofol can alleviate injuries caused by heat stress, LPS, or the combination of heat stress and LPS. Interestingly, propofol can only mitigate LPS-induced intestinal epithelial cell apoptosis, and has no protective role in heat-stress-induced apoptosis. This study developed a model that can mimic the intestinal heat stress environment. It demonstrates the effects on intestinal epithelial cell damage, and indicated that propofol could be used as a therapeutic drug for the treatment of heat-stress-induced intestinal injuries.

  11. Effects of propofol on damage of rat intestinal epithelial cells induced by heat stress and lipopolysaccharides

    International Nuclear Information System (INIS)

    Tang, J.; Jiang, Y.; Tang, Y.; Chen, B.; Sun, X.; Su, L.; Liu, Z.

    2013-01-01

    Gut-derived endotoxin and pathogenic bacteria have been proposed as important causative factors of morbidity and death during heat stroke. However, it is still unclear what kind of damage is induced by heat stress. In this study, the rat intestinal epithelial cell line (IEC-6) was treated with heat stress or a combination of heat stress and lipopolysaccharide (LPS). In addition, propofol, which plays an important role in anti-inflammation and organ protection, was applied to study its effects on cellular viability and apoptosis. Heat stress, LPS, or heat stress combined with LPS stimulation can all cause intestinal epithelial cell damage, including early apoptosis and subsequent necrosis. However, propofol can alleviate injuries caused by heat stress, LPS, or the combination of heat stress and LPS. Interestingly, propofol can only mitigate LPS-induced intestinal epithelial cell apoptosis, and has no protective role in heat-stress-induced apoptosis. This study developed a model that can mimic the intestinal heat stress environment. It demonstrates the effects on intestinal epithelial cell damage, and indicated that propofol could be used as a therapeutic drug for the treatment of heat-stress-induced intestinal injuries

  12. Intestinal Barrier and Behavior.

    Science.gov (United States)

    Julio-Pieper, M; Bravo, J A

    2016-01-01

    The intestinal barrier function contributes to gut homeostasis by modulating absorption of water, electrolytes, and nutrients from the lumen into the circulation while restricting the passage of noxious luminal substances and microorganisms. Chronic conditions such as rheumatoid arthritis, inflammatory bowel disease, and celiac disease are associated to intestinal barrier dysfunction. Here, the hypothesis is that a leaky intestinal wall allowing for indiscriminate passage of intraluminal compounds to the vascular compartment could in turn lead to systemic inflammation. An increasing number of studies are now investigating the association between gut permeability and CNS disorders, under the premise that translocation of intestinal luminal contents could affect CNS function, either directly or indirectly. Still, it is unknown whether disruption of intestinal barrier is a causative agent or a consequence in these situations. Here, we discuss the latest evidence pointing to an association between increased gut permeability and disrupted behavioral responses. © 2016 Elsevier Inc. All rights reserved.

  13. Modification in oxidative stress, inflammation, and lipoprotein assembly in response to hepatocyte nuclear factor 4alpha knockdown in intestinal epithelial cells.

    Science.gov (United States)

    Marcil, Valérie; Seidman, Ernest; Sinnett, Daniel; Boudreau, François; Gendron, Fernand-Pierre; Beaulieu, Jean-François; Ménard, Daniel; Precourt, Louis-Philippe; Amre, Devendra; Levy, Emile

    2010-12-24

    Hepatocyte nuclear factor 4α (HNF4α) is a nuclear transcription factor mainly expressed in the liver, intestine, kidney, and pancreas. Many of its hepatic and pancreatic functions have been described, but limited information is available on its role in the gastrointestinal tract. The objectives of this study were to evaluate the anti-inflammatory and antioxidant functions of HNF4α as well as its implication in intestinal lipid transport and metabolism. To this end, the HNF4A gene was knocked down by transfecting Caco-2 cells with a pGFP-V-RS lentiviral vector containing an shRNA against HNF4α. Inactivation of HNF4α in Caco-2 cells resulted in the following: (a) an increase in oxidative stress as demonstrated by the levels of malondialdehyde and conjugated dienes; (b) a reduction in secondary endogenous antioxidants (catalase, glutathione peroxidase, and heme oxygenase-1); (c) a lower protein expression of nuclear factor erythroid 2-related factor that controls the antioxidant response elements-regulated antioxidant enzymes; (d) an accentuation of cellular inflammatory activation as shown by levels of nuclear factor-κB, interleukin-6, interleukin-8, and leukotriene B4; (e) a decrease in the output of high density lipoproteins and of their anti-inflammatory and anti-oxidative components apolipoproteins (apo) A-I and A-IV; (f) a diminution in cellular lipid transport revealed by a lower cellular secretion of chylomicrons and their apoB-48 moiety; and (g) alterations in the transcription factors sterol regulatory element-binding protein 2, peroxisome proliferator-activated receptor α, and liver X receptor α and β. In conclusion, HNF4α appears to play a key role in intestinal lipid metabolism as well as intestinal anti-oxidative and anti-inflammatory defense mechanisms.

  14. Sustained TL1A (TNFSF15) expression on both lymphoid and myeloid cells leads to mild spontaneous intestinal inflammation and fibrosis

    Science.gov (United States)

    Zheng, Libo; Zhang, Xiaolan; Chen, Jeremy; Ichikawa, Ryan; Wallace, Kori; Pothoulakis, Charalabos; Koon, Hon Wai

    2013-01-01

    TL1A is a member of the TNF superfamily, and its expression is increased in the mucosa of inflammatory bowel disease patients. Moreover, patients with certain TNFSF15 variants over-express TL1A and have a higher risk of developing strictures in the small intestine. Consistently, mice with sustained Tl1a expression in either lymphoid or myeloid cells develop spontaneous ileitis and increased intestinal collagen deposition. Transgenic (Tg) mice with constitutive Tl1a expression in both lymphoid and myeloid cells were generated to assess their in vivo consequence. Constitutive expression of Tl1a in both lymphoid and myeloid cells showed increased spontaneous ileitis and collagen deposition than WT mice. T cells with constitutive expression of Tl1a in both lymphoid and myeloid cells were found to have a more activated phenotype, increased gut homing marker CCR9 expression, and enhanced Th1 and Th17 cytokine activity than WT mice. Although no differences in T cell activation marker, Th1 or Th17 cytokine activity, ileitis, or collagen deposition were found between constitutive Tl1a expression in lymphoid only, myeloid only, or combined lymphoid and myeloid cells. Double hemizygous Tl1a-Tg mice appeared to have worsened ileitis and intestinal fibrosis. Our findings confirm that TL1A–DR3 interaction is involved in T cell-dependent ileitis and fibrosis. PMID:23638306

  15. Citrus tachibana Leaves Ethanol Extract Alleviates Airway Inflammation by the Modulation of Th1/Th2 Imbalance via Inhibiting NF-κB Signaling and Histamine Secretion in a Mouse Model of Allergic Asthma.

    Science.gov (United States)

    Bui, Thi Tho; Piao, Chun Hua; Kim, Soo Mi; Song, Chang Ho; Shin, Hee Soon; Lee, Chang-Hyun; Chai, Ok Hee

    2017-07-01

    Asthma is a chronic inflammatory disease of bronchial airway, which is characterized by chronic airway inflammation, airway edema, goblet cell hyperplasia, the aberrant production of the Th2 cytokines, and eosinophil infiltration in the lungs. In this study, the therapeutic effect and the underlying mechanism of Citrus tachibana leaves ethanol extract (CTLE) in the ovalbumin (OVA)-induced allergic asthma and compound 48/80-induced anaphylaxis were investigated. Oral administration of CTLE inhibited OVA-induced asthmatic response by reducing airway inflammation, OVA-specific IgE and IgG1 levels, and increasing OVA-specific IgG2a levels. CTLE restored Th1/Th2 balance through an increase in Th2 cytokines tumor necrosis factor-α, interleukin (IL)-4, and IL-6 and decreases in Th1 cytokines interferon-γ and IL-12. Furthermore, CTLE inhibited the total level of NF-κB and the phosphorylation of IκB-α and NF-κB by OVA. In addition, CTLE dose-dependently inhibited compound 48/80-induced anaphylaxis via blocking histamine secretion from mast cells. The anti-inflammatory mechanism of CTLE may involve the modulation of Th1/Th2 imbalance via inhibiting the NF-κB signaling and histamine secretion. Taken together, we suggest that CTLE could be used as a therapeutic agent for patients with Th2-mediated or histamine-mediated allergic asthma.

  16. Oral Administration of Probiotics Inhibits Absorption of the Heavy Metal Cadmium by Protecting the Intestinal Barrier.

    Science.gov (United States)

    Zhai, Qixiao; Tian, Fengwei; Zhao, Jianxin; Zhang, Hao; Narbad, Arjan; Chen, Wei

    2016-07-15

    The heavy metal cadmium (Cd) is an environmental pollutant that causes adverse health effects in humans and animals. Our previous work demonstrated that oral administration of probiotics can significantly inhibit Cd absorption in the intestines of mice, but further evidence is needed to gain insights into the related protection mode. The goal of this study was to evaluate whether probiotics can inhibit Cd absorption through routes other than the Cd binding, with a focus on gut barrier protection. In the in vitro assay, both the intervention and therapy treatments of Lactobacillus plantarum CCFM8610 alleviated Cd-induced cytotoxicity in the human intestinal cell line HT-29 and protected the disruption of tight junctions in the cell monolayers. In a mouse model, probiotics with either good Cd-binding or antioxidative ability increased fecal Cd levels and decreased Cd accumulation in the tissue of Cd-exposed mice. Compared with the Cd-only group, cotreatment with probiotics also reversed the disruption of tight junctions, alleviated inflammation, and decreased the intestinal permeability of mice. L. plantarum CCFM8610, a strain with both good Cd binding and antioxidative abilities, exhibited significantly better protection than the other two strains. These results suggest that along with initial intestinal Cd sequestration, probiotics can inhibit Cd absorption by protecting the intestinal barrier, and the protection is related to the alleviation of Cd-induced oxidative stress. A probiotic with both good Cd-binding and antioxidative capacities can be used as a daily supplement for the prevention of oral Cd exposure. The heavy metal cadmium (Cd) is an environmental pollutant that causes adverse health effects in humans and animals. For the general population, food and drinking water are the main sources of Cd exposure due to the biomagnification of Cd within the food chain; therefore, the intestinal tract is the first organ that is susceptible to Cd contamination

  17. Inositoylated platelet-activating factor (Ino-C2-PAF) modulates dynamic lymphocyte-endothelial cell interactions and alleviates psoriasis-like skin inflammation in two complementary mouse models.

    Science.gov (United States)

    Forkel, Susann; Schön, Margarete; Hildmann, Annette; Claßen, Anna; John, Swen-Malte; Danker, Kerstin; Schön, Michael P

    2014-10-01

    Psoriasis, a tumor necrosis factor alpha (TNFα)-governed inflammatory disorder with prominent dysregulation of cutaneous vascular functions, has evolved into a model disorder for studying anti-inflammatory therapies. We present experimental in vitro and in vivo data on 1-O-octadecyl-2-O-(2-(myo-inositolyl)-ethyl)-sn-glycero-3-(R/S)-phosphatidyl-choline (Ino-C2-PAF), the lead compound of a class of synthetic glycosylated phospholipids, in anti-inflammatory therapy. Ino-C2-PAF strongly induced apoptosis only in TNFα-stimulated, but not in untreated human vascular endothelial cells. Moreover, TNFα-induced endothelial adhesion molecules that mediated the rolling and firm adhesion of leukocytes (vascular cell adhesion protein-1 (VCAM-1), E-selectin, and ICAM-1) were selectively downregulated by Ino-C2-PAF. Similarly, expression of L-selectin, VCAM-1 receptor α4β1 integrin , and lymphocyte function-associated antigen-1 on human peripheral blood mononuclear cells was reduced without induction of apoptosis. Functionally, these changes were accompanied by significant impairment of rolling and adhesion of human peripheral blood lymphocytes on TNFα-activated endothelial cells in a dynamic flow chamber system. When the therapeutic potential of Ino-C2-PAF was assessed in two complementary mouse models of psoriasis, K5.hTGFβ1 transgenic and JunB/c-Jun-deficient mice, Ino-C2-PAF led to significant alleviation of the clinical symptoms and normalized the pathological cutaneous changes including vascularization. There were no overt adverse effects. These findings suggested that Ino-C2-PAF is a potential candidate in the therapy of inflammatory skin diseases that include abnormal vascular functions.

  18. Arctigenin Confers Neuroprotection Against Mechanical Trauma Injury in Human Neuroblastoma SH-SY5Y Cells by Regulating miRNA-16 and miRNA-199a Expression to Alleviate Inflammation.

    Science.gov (United States)

    Song, Jie; Li, Na; Xia, Yang; Gao, Zhong; Zou, Sa-Feng; Yan, Yu-Hui; Li, Shao-Heng; Wang, Yue; Meng, Ya-Kun; Yang, Jing-Xian; Kang, Ting-Guo

    2016-09-01

    Mechanical trauma injury is a severe insult to neural cells. Subsequent secondary injury involves the release of inflammatory factors that have dramatic consequences for undamaged cells, leading to normal cell death after the initial injury. The present study investigated the capacity for arctigenin (ARC) to prevent secondary effects and evaluated the mechanism underlying the action of microRNA (miRNA)-199a and miRNA-16 in a mechanical trauma injury (MTI) model using SH-SY5Y cells in vitro. SH-SY5Y cells are often applied to in vitro models of neuronal function and differentiation. Recently, miRNAs have been demonstrated to play a crucial role in NF-κB and cholinergic signaling, which can regulate inflammation. The cell model was established by scratch-induced injury of human SH-SY5Y cells, which mimics the characteristics of MTI. A cell counting kit-8 (CCK-8), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and immunocytochemistry were used to measure cell viability. Enzyme-linked immunosorbent assay (ELISA) was used to evaluate the inflammatory cytokine and cholinesterase (CHE) content. The lactate dehydrogenase (LDH) content was measured to assess the degree of cell injury. The mRNA levels were measured by RT-PCR to analyze ARC's mechanism of action. miRNA inhibitors and mimics were used to inhibit and strengthen the expression of miRNAs. Protein expression was detected by western blotting analysis. ARC treatment reduced the TNF-α and IL-6 levels as well as the number of TUNEL+ apoptotic SH-SY5Y cells surrounding the scratch and increased the IL-10 level compared to the controls. ARC attenuated the increase of the cell damage degree and LDH content induced by scratching, indicating increased cell survival. Mechanistic studies showed that ARC upregulated the miRNA-16 and miRNA-199a levels to reduce upstream protein (IKKα and IKKβ) expression and inhibit NF-κB signaling pathway activity; moreover, the increased miRNA-199a suppresses

  19. Fortunellin-Induced Modulation of Phosphatase and Tensin Homolog by MicroRNA-374a Decreases Inflammation and Maintains Intestinal Barrier Function in Colitis

    Directory of Open Access Journals (Sweden)

    Yongjian Xiong

    2018-01-01

    Full Text Available Activation of phosphatase and tensin homolog (PTEN is known to induce cell apoptosis. MicroRNA-374a (miR-374a, which can suppress PTEN expression, has been found abnormally expressed in inflammatory bowel disease (IBD. Fortunellin is a citrus flavonoid that is a potential anti-inflammation agent in inflammatory diseases. The present study investigated the effects and mechanisms underlying fortunellin-induced inhibition of PTEN in IBD. Colitis was established in rats by the intracolonic administration of 2,4,6-trinitrobenzene sulfonic acid to mimic human ulcerative colitis, which is the main type of IBD. miR-374a expression was measured by quantitative real-time polymerase chain reaction, and the regulation of PTEN by miR-374a was evaluated by dual luciferase reporter assay. Western blotting was used to measure the corresponding protein expression. Fortunellin ameliorated colitis symptoms, including excessive inflammation and oxidative stress. Fortunellin decreased epithelial cell apoptosis through inhibiting PTEN expression in colitis. Fortunellin-induced downregulation of PTEN could be counteracted by miR-374a depletion. Moreover, knockdown of miR-374a in vivo partly inhibited the effects of fortunellin on rat colitis. In conclusion, PTEN inhibition contributes to the amelioration effects of fortunellin on colitis. It was confirmed that fortunellin targets miR-374a, which is a negative regulator of PTEN. This study provides novel insights into the pathological mechanisms and treatment alternatives of colitis.

  20. Intestinal Cancer

    Science.gov (United States)

    ... connects your stomach to your large intestine. Intestinal cancer is rare, but eating a high-fat diet ... increase your risk. Possible signs of small intestine cancer include Abdominal pain Weight loss for no reason ...

  1. Anti-inflammatory effect of sugar-amino acid Maillard reaction products on intestinal inflammation model in vitro and in vivo.

    Science.gov (United States)

    Oh, Jun-Gu; Chun, Su-Hyun; Kim, Da Hyun; Kim, Jin Hye; Shin, Hye Soo; Cho, Yong Soo; Kim, Yong Ki; Choi, Hee-Don; Lee, Kwang-Won

    2017-09-08

    The Maillard reaction is a nonenzymatic reaction between an amino acid and a reducing sugar that usually occurs upon heating. This reaction occurs routinely in cooking, generates numerous products, which are collectively referred to as Maillard reaction products (MRPs) contributing to aroma and color features. Advanced glycation end-products (AGEs) transformed from MRPs are participated in many types of inflammation reaction. In this study, various sugar-amino acid MRPs were prepared from three different amino acids (lysine, arginine, and glycine) and sugars (glucose, fructose, and galactose) for 1 h with heating at 121 °C. Treatment of lipopolysaccharide-stimulated RAW264.7 macrophages with the MRPs decreased nitric oxide (NO) expression compared to control without MRPs treatment. MRPs derived from lysine and galactose (Lys-Gal MRPs) significantly inhibited NO expression. The retentate fraction of Lys-Gal MRPs with cut-off of molecular weight of 3-10 kDa (LGCM) suppressed NO expression more effectively than did Lys-Gal MRPs. The anti-inflammatory effect of LGCM was evaluated using a co-culture system consisting of Caco-2 (apical side) and RAW264.7 or THP-1 (basolateral side) cells to investigate the gut inflammation reaction by stimulated macrophage cells. In this system, LGCM prevented a decreased transepithelial electrical resistance, and decreased both tumor necrosis factor-α production in macrophages and interleukin (IL)-8 and IL-1β mRNA expression in Caco-2 cells. In co-culture and in vivo dextran sulfate sodium (DSS)-induced colitis model study, we also observed the anti-inflammatory activity of LGCM. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Mycotoxins and the intestine

    Directory of Open Access Journals (Sweden)

    Leon Broom

    2015-12-01

    Full Text Available Fungal biochemical pathways can yield various compounds that are not considered to be necessary for their growth and are thus referred to as secondary metabolites. These compounds have been found to have wide ranging biological effects and include potent poisons (mycotoxins. Mycotoxins invariably contaminate crops and (thus animal feeds. The intestine is the key link between ingested mycotoxins and their detrimental effects on the animal. Effects on the intestine, or intestinal environment, and immune system have been reported with various mycotoxins. These effects are almost certainly occurring across species. Most, if not all, of the reported effects of mycotoxins are negative in terms of intestinal health, for example, decreased intestinal cell viability, reductions in short chain fatty acid (SCFA concentrations and elimination of beneficial bacteria, increased expression of genes involved in promoting inflammation and counteracting oxidative stress. This challenge to intestinal health will predispose the animal to intestinal (and systemic infections and impair efficient digestion and absorption of nutrients, with the associated effect on animal productivity.

  3. Placental growth factor enhances angiogenesis in human intestinal microvascular endothelial cells via PI3K/Akt pathway: Potential implications of inflammation bowel disease

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Yi, E-mail: mondayzy@126.com; Tu, Chuantao, E-mail: tu.chuantao@zs-hospital.sh.cn; Zhao, Yuan, E-mail: zhao.yuan@zs-hospital.sh.cn; Liu, Hongchun, E-mail: liuhch@aliyun.com; Zhang, Shuncai, E-mail: zhang.shuncai@zs-hospital.sh.cn

    2016-02-19

    Background: Angiogenesis plays a major role in the pathogenesis of inflammatory bowel disease (IBD). Placental growth factor (PlGF) is a specific regulator of pathological angiogenesis and is upregulated in the sera of IBD patients. Therefore, the role of PlGF in IBD angiogenesis was investigated here using HIMECs. Methods: The expression of PlGF and its receptors in human intestinal microvascular endothelial cells (HIMECs) and inflamed mucosa of IBD patients were examined using quantitative PCR and western blot analysis and the role of PlGF in IBD HIMECs was further explored using small interfering RNA (siRNA). The induction of pro-inflammatory cytokine by PlGF in HIMECs was confirmed by ELISA. The capacity of PlGF to induce angiogenesis in HIMECs was tested through proliferation, cell-migration, matrigel tubule-formation assays and its underlying signaling pathway were explored by western blot analysis of ERK1/2 and PI3K/Akt phosphorylation. Results: mRNA and protein expression of PlGF and its receptor NRP-1 were significantly increased in IBD HIMECs. Inflamed mucosa of IBD patients also displayed higher expression of PIGF. The production of IL-6 and TNF-α in culture supernatant of HIMECs treated with exogenous recombinant human PlGF-1 (rhPlGF-1) were increased. Furthermore, rhPlGF-1 significantly induced HIMECs migration and tube formation in a dose-dependent manner and knockdown of endogenous PlGF in IBD HIMECs using siRNA substantially reduced these angiogenesis activities. PlGF induced PI3K/Akt phosphorylation in HIMECs and pretreatment of PlGF-stimulated HIMECs with PI3K inhibitor (LY294002) significantly inhibited the PlGF-induced cell migration and tube formation. Conclusion: Our results demonstrated the pro-inflammatory and angiogenic effects of PlGF on HIMECs in IBD through activation of PI3K/Akt signaling pathway. PlGF/PI3K/Akt signaling may serve as a potential therapeutic target for IBD. - Highlights: • Expression of PlGF and its receptor NRP-1

  4. Dietary iron enhances colonic inflammation and IL-6/IL-11-Stat3 signaling promoting colonic tumor development in mice.

    Directory of Open Access Journals (Sweden)

    Anita C G Chua

    Full Text Available Chronic intestinal inflammation and high dietary iron are associated with colorectal cancer development. The role of Stat3 activation in iron-induced colonic inflammation and tumorigenesis was investigated in a mouse model of inflammation-associated colorectal cancer. Mice, fed either an iron-supplemented or control diet, were treated with azoxymethane and dextran sodium sulfate (DSS. Intestinal inflammation and tumor development were assessed by endoscopy and histology, gene expression by real-time PCR, Stat3 phosphorylation by immunoblot, cytokines by ELISA and apoptosis by TUNEL assay. Colonic inflammation was more severe in mice fed an iron-supplemented compared with a control diet one week post-DSS treatment, with enhanced colonic IL-6 and IL-11 release and Stat3 phosphorylation. Both IL-6 and ferritin, the iron storage protein, co-localized with macrophages suggesting iron may act directly on IL-6 producing-macrophages. Iron increased DSS-induced colonic epithelial cell proliferation and apoptosis consistent with enhanced mucosal damage. DSS-treated mice developed anemia that was not alleviated by dietary iron supplementation. Six weeks post-DSS treatment, iron-supplemented mice developed more and larger colonic tumors compared with control mice. Intratumoral IL-6 and IL-11 expression increased in DSS-treated mice and IL-6, and possibly IL-11, were enhanced by dietary iron. Gene expression of iron importers, divalent metal transporter 1 and transferrin receptor 1, increased and iron exporter, ferroportin, decreased in colonic tumors suggesting increased iron uptake. Dietary iron and colonic inflammation synergistically activated colonic IL-6/IL-11-Stat3 signaling promoting tumorigenesis. Oral iron therapy may be detrimental in inflammatory bowel disease since it may exacerbate colonic inflammation and increase colorectal cancer risk.

  5. Mango polyphenolics reduce inflammation in intestinal colitis-involvement of the miR-126/PI3K/AKT/mTOR axis in vitro and in vivo.

    Science.gov (United States)

    Kim, Hyemee; Banerjee, Nivedita; Barnes, Ryan C; Pfent, Catherine M; Talcott, Stephen T; Dashwood, Roderick H; Mertens-Talcott, Susanne U

    2017-01-01

    This study sought to elucidate the mechanisms underlying the anti-inflammatory effect of mango (Mangifera Indica L.) polyphenolics containing gallic acid and gallotanins, and the role of the miR-126/PI3K/AKT/mTOR signaling axis in vitro and in vivo. Polyphenolics extracted from mango (var. Keitt) were investigated in lipopolysaccharide (LPS)-treated CCD-18Co cells. Rats received either a beverage with mango polyphenolics or a control beverage, and were exposed to three cycles of 3% dextran sodium sulfate (DSS) followed by a 2-wk recovery period. The mango extract (10 mg GAE/L) suppressed the protein expression of NF-κB, p-NF-κB, PI3K (p85β), HIF-1α, p70S6K1, and RPS6 in LPS-treated CCD-18Co cells. LPS reduced miR-126 expression, whereas, the mango extract induced miR-126 expression in a dose-dependent manner. The relationship between miR-126 and its target, PI3K (p85β), was confirmed by treating cells with miR-126 antagomiR where mango polyphenols reversed the effects of the antagomiR. In vivo, mango beverage protected against DSS-induced colonic inflammation (47%, P = 0.05) and decreased the Ki-67 labeling index in the central and basal regions compared to the control. Mango beverage significantly attenuated the expression of pro-inflammatory cytokines such as TNF-α, IL-1β, and iNOS at the mRNA and protein level. Moreover, the expression of PI3K, AKT, and mTOR was reduced, whereas, miR-126 was upregulated by the mango treatment. These results suggest that mango polyphenols attenuated inflammatory response by modulating the PI3K/AKT/mTOR pathway at least in part through upregulation of miRNA-126 expression both in vitro and in vivo; thus, mango polyphenolics might be relevant as preventive agents in ulcerative colitis. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  6. Mango Polyphenolics Reduce Inflammation in Intestinal Colitis—Involvement of the miR-126/PI3K/AKT/mTOR Axis In Vitro and In Vivo

    Science.gov (United States)

    Kim, Hyemee; Banerjee, Nivedita; Barnes, Ryan C.; Pfent, Catherine M.; Talcott, Stephen T.; Dashwood, Roderick H.; Mertens-Talcott, Susanne U.

    2016-01-01

    This study sought to elucidate the mechanisms underlying the anti-inflammatory effect of mango (Mangifera Indica L.) polyphenolics containing gallic acid and gallotanins, and the role of the miR-126/PI3K/AKT/mTOR signaling axis in vitro and in vivo. Polyphenolics extracted from mango (var. Keitt) were investigated in lipopolysaccharide (LPS)-treated CCD-18Co cells. Rats received either a beverage with mango polyphenolics or a control beverage, and were exposed to three cycles of 3% dextran sodium sulfate (DSS) followed by a 2-wk recovery period. The mango extract (10 mg GAE/L) suppressed the protein expression of NF-κB, p-NF-κB, PI3K (p85β), HIF-1α, p70S6K1, and RPS6 in LPS-treated CCD-18Co cells. LPS reduced miR-126 expression, whereas, the mango extract induced miR-126 expression in a dose-dependent manner. The relationship between miR-126 and its target, PI3K (p85β), was confirmed by treating cells with miR-126 antagomiR where mango polyphenols reversed the effects of the antagomiR. In vivo, mango beverage protected against DSS-induced colonic inflammation (47%, P = 0.05) and decreased the Ki-67 labeling index in the central and basal regions compared to the control. Mango beverage significantly attenuated the expression of pro-inflammatory cytokines such as TNF-α, IL-1β, and iNOS at the mRNA and protein level. Moreover, the expression of PI3K, AKT, and mTOR was reduced, whereas, miR-126 was upregulated by the mango treatment. These results suggest that mango polyphenols attenuated inflammatory response by modulating the PI3K/AKT/mTOR pathway at least in part through upregulation of miRNA-126 expression both in vitro and in vivo; thus, mango polyphenolics might be relevant as preventive agents in ulcerative colitis. PMID:27061150

  7. Reactivation of Intestinal Inflammation Is Suppressed by Catestatin in a Murine Model of Colitis via M1 Macrophages and Not the Gut Microbiota

    Directory of Open Access Journals (Sweden)

    Mohammad F. Rabbi

    2017-08-01

    Full Text Available While there is growing awareness of a relationship between chromogranin-A (CHGA and susceptibility to inflammatory conditions, the role of human catestatin [(hCTS; CHGA352–67] in the natural history of established inflammatory bowel disease is not known. Recently, using two different experimental models, we demonstrated that hCTS-treated mice develop less severe acute colitis. We have also shown the implication of the macrophages in this effect. The aims of this study were to determine (1 whether hCTS treatment could attenuate the reactivation of inflammation in adult mice with previously established chronic colitis; (2 whether this effect is mediated through macrophages or the gut microbiota. Quiescent colitis was induced in 7–8-week-old C57BL6 mice using four cycles (2–4% of dextran sulfate sodium. hCTS (1.5 mg/kg/day treatment or vehicle started 2 days before the last induction of colitis and continuing for 7 days. At sacrifice, macro- and microscopic scores were determined. Colonic pro-inflammatory cytokines [interleukin (IL-6, IL-1β, and TNF- α], anti-inflammatory cytokines (IL-10, TGF- β, classically activated (M1 (iNOS, Mcp1, and alternatively activated (M2 (Ym1, Arg1 macrophages markers were studied using ELISA and/or RT-qPCR. In vitro, peritoneal macrophages isolated from naïve mice and treated with hCTS (10−5 M, 12 h were exposed to either lipopolysaccharide (100 ng/ml, 12 h to polarize M1 macrophages or to IL-4/IL-13 (20 ng/ml to polarize M2 macrophages. M1/M2 macrophage markers along with cytokine gene expression were determined using RT-qPCR. Feces and mucosa-associated microbiota (MAM samples were collected, and the V4 region of 16 s rRNA was sequenced. Micro- and macroscopic scores, colonic IL-6, IL-1β, TNF- α, and M1 macrophages markers were significantly decreased in the hCTS-treated group. Treatment did not have any effect on colonic IL-10, TGF-β, and M2 markers nor modified the bacterial

  8. Lactococcus lactis carrying the pValac eukaryotic expression vector coding for IL-4 reduces chemically-induced intestinal inflammation by increasing the levels of IL-10-producing regulatory cells.

    Science.gov (United States)

    Souza, Bianca Mendes; Preisser, Tatiane Melo; Pereira, Vanessa Bastos; Zurita-Turk, Meritxell; de Castro, Camila Prósperi; da Cunha, Vanessa Pecini; de Oliveira, Rafael Pires; Gomes-Santos, Ana Cristina; de Faria, Ana Maria Caetano; Machado, Denise Carmona Cara; Chatel, Jean-Marc; Azevedo, Vasco Ariston de Carvalho; Langella, Philippe; Miyoshi, Anderson

    2016-08-30

    Inflammatory bowel diseases are characterized by chronic intestinal inflammation that leads to severe destruction of the intestinal mucosa. Therefore, the understanding of their aetiology as well as the development of new medicines is an important step for the treatment of such diseases. Consequently, the development of Lactococcus lactis strains capable of delivering a eukaryotic expression vector encoding the interleukin 4 (IL-4) of Mus musculus would represent a new strategy for the elaboration of a more effective alternative therapy against Crohn's disease. The murine IL-4 ORF was cloned into the eukaryotic expression vector pValac::dts. The resulting plasmid-pValac::dts::IL-4-was transfected into CHO cells so that its functionality could be evaluated in vitro. With fluorescent confocal microscopy, flow cytometry and ELISA, it was observed that pValac::dts::IL-4-transfected cells produced IL-4, while non-transfected cells and cells transfected with the empty vector did not. Then, pValac::dts::IL-4 was inserted into L. lactis MG1363 FnBPA(+) in order to evaluate the therapeutic potential of the recombinant strain against TNBS-induced colitis. Intragastric administration of L. lactis MG1363 FnBPA(+) (pValac::dts::IL-4) was able to decrease the severity of colitis, with animals showing decreased levels of IL-12, IL-6 and MPO activity; and increased levels of IL-4 and IL-10. Finally, LP-isolated cells from mice administered TNBS were immunophenotyped so that the main IL-4 and IL-10 producers were identified. Mice administered the recombinant strain presented significantly higher percentages of F4/80(+)MHCII(+)Ly6C(-)IL-4(+), F4/80(+)MHCII(+)Ly6C(-)IL-10(+), F4/80(+)MHCII(+)Ly6C(-)CD206(+)CD124(+)IL-10(+) and CD4(+)Foxp3(+)IL10(+) cells compared to the other groups. This study shows that L. lactis MG1363 FnBPA(+) (pValac::dts::IL-4) is a good candidate to maintain the anti-inflammatory and proinflammatory balance in the gastrointestinal tract, increasing the levels

  9. Midkine in Inflammation

    Directory of Open Access Journals (Sweden)

    Ludwig T. Weckbach

    2011-01-01

    Full Text Available The 13 kDa heparin-binding growth factor midkine (MK was originally identified as a molecule involved in the orchestration of embryonic development. Recent studies provided evidence for a new role of MK in acute and chronic inflammatory processes. Accordingly, several inflammatory diseases including nephritis, arthritis, atherosclerosis, colitis, and autoimmune encephalitis have been shown to be alleviated in the absence of MK in animal models. Reduced leukocyte recruitment to the sites of inflammation was found to be one important mechanism attenuating chronic inflammation when MK was absent. Furthermore, MK was found to modulate expression of proinflammatory cytokines and the expansion of regulatory T-cells. Here, we review the current understanding of the role of MK in different inflammatory disorders and summarize the knowledge of MK biology.

  10. Retroperitoneal inflammation

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/001255.htm Retroperitoneal inflammation To use the sharing features on this page, please enable JavaScript. Retroperitoneal inflammation is swelling that occurs in the retroperitoneal space. ...

  11. Polyopes affinis alleviates airway inflammation in a murine model of ...

    Indian Academy of Sciences (India)

    The successive intraperitoneal administration of P. affinis ethanolic extracts before the last airway OVA-challenge resulted in a significant inhibition of all asthmatic reactions. These data suggest that P. affinis ethanolic extracts possess therapeutic potential for the treatment of pulmonary allergic disorders such as allergic ...

  12. Polyopes affinis alleviates airway inflammation in a murine model of ...

    Indian Academy of Sciences (India)

    Athukorala Y, Jung WK, Park PJ, Lee YJ, Kim SK, Vasanthan T,. No HK and Jeon YJ 2008 Evaluation of biomolecular interactions of sulfated polysaccharide isolated from Grate- loupia filicina on blood coagulation factors. J. Microbiol. Biotechnol. 18 503–511. Barnes PJ 1994 Cytokines as mediators of chronic asthma. Am.

  13. Pomegranate polyphenolics reduce inflammation and ulceration in intestinal colitis-involvement of the miR-145/p70S6K1/HIF1α axis in vivo and in vitro.

    Science.gov (United States)

    Kim, Hyemee; Banerjee, Nivedita; Sirven, Maritza A; Minamoto, Yasushi; Markel, Melissa E; Suchodolski, Jan S; Talcott, Stephen T; Mertens-Talcott, Susanne U

    2017-05-01

    This study investigated the potential role of the p70S6K1/HIF1α axis in the anti-inflammatory activities of pomegranate (Punica granatum L.) polyphenolics in dextran sodium sulfate (DSS)-induced colitis in Sprague-Dawley rats and in lipopolysaccharide (LPS)-treated CCD-18Co colon-myofibroblastic cells. Rats were administered either control (CT) or pomegranate beverage (PG), containing ellagic acid and ellagitannins, then exposed to three cycles of 3% DSS followed by a 2-week recovery period. PG protected against DSS-induced colon inflammation and ulceration (50% and 66.7%, P=.05 and .045, respectively), and decreased the Ki-67 proliferative index in the central and basal regions compared to the control. PG also significantly reduced the expression of proinflammatory cytokines (TNF-α and IL-1β), COX-2, and iNOS at mRNA and protein levels. In addition, the expression of p70S6K1 and HIF1α was reduced, while the tumor suppressor miR-145 was induced by PG. The intestinal microbiota of rats treated with PG showed a significant increase in Ruminococcaceae that include several butyrate producing bacteria (P=.03). In vitro, PG reduced the expression of p70S6K1 and HIF1α and induced miR-145 in a dose-dependent manner. The involvement of miR-145/p70S6K1 was confirmed by treating LPS-treated CCD-18Co cells with miR-145 antagomiR, where the pomegranate polyphenolics reversed the effects of the antagomiR for p70S6K1 mRNA and protein levels. These results suggest that pomegranate polyphenols attenuated DSS-induced colitis by modulating the miR-145/p70S6K/HIF1α axis, indicating potential use in therapeutic treatment of ulcerative colitis. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Intestinal Obstruction

    Science.gov (United States)

    ... the obstruction along the intestines. Treatment Suction via nasogastric tube Fluids given by vein Surgery for strangulation Sometimes ... nose and placed in the stomach (called a nasogastric tube) or into the intestine. Suction is applied to ...

  15. Impact of the Gut Microbiota on Intestinal Immunity Mediated by Tryptophan Metabolism

    Science.gov (United States)

    Gao, Jing; Xu, Kang; Liu, Hongnan; Liu, Gang; Bai, Miaomiao; Peng, Can; Li, Tiejun; Yin, Yulong

    2018-01-01

    The gut microbiota influences the health of the host, especially with regard to gut immune homeostasis and the intestinal immune response. In addition to serving as a nutrient enhancer, L-tryptophan (Trp) plays crucial roles in the balance between intestinal immune tolerance and gut microbiota maintenance. Recent discoveries have underscored that changes in the microbiota modulate the host immune system by modulating Trp metabolism. Moreover, Trp, endogenous Trp metabolites (kynurenines, serotonin, and melatonin), and bacterial Trp metabolites (indole, indolic acid, skatole, and tryptamine) have profound effects on gut microbial composition, microbial metabolism, the host's immune system, the host-microbiome interface, and host immune system–intestinal microbiota interactions. The aryl hydrocarbon receptor (AhR) mediates the regulation of intestinal immunity by Trp metabolites (as ligands of AhR), which is beneficial for immune homeostasis. Among Trp metabolites, AhR ligands consist of endogenous metabolites, including kynurenine, kynurenic acid, xanthurenic acid, and cinnabarinic acid, and bacterial metabolites, including indole, indole propionic acid, indole acetic acid, skatole, and tryptamine. Additional factors, such as aging, stress, probiotics, and diseases (spondyloarthritis, irritable bowel syndrome, inflammatory bowel disease, colorectal cancer), which are associated with variability in Trp metabolism, can influence Trp–microbiome–immune system interactions in the gut and also play roles in regulating gut immunity. This review clarifies how the gut microbiota regulates Trp metabolism and identifies the underlying molecular mechanisms of these interactions. Increased mechanistic insight into how the microbiota modulates the intestinal immune system through Trp metabolism may allow for the identification of innovative microbiota-based diagnostics, as well as appropriate nutritional supplementation of Trp to prevent or alleviate intestinal inflammation

  16. Effects of probiotic Lactobacillus rhamnosus GG and Propionibacterium freudenreichii ssp. shermanii JS supplementation on intestinal and systemic markers of inflammation in ApoE*3Leiden mice consuming a high-fat diet

    NARCIS (Netherlands)

    Oksaharju, A.; Kooistra, T.; Kleemann, R.; Duyvenvoorde, W. van; Miettinen, M.; Lappalainen, J.; Lindstedt, K.A.; Kovanen, P.T.; Korpela, R.; Kekkonen, R.A.

    2013-01-01

    A high-fat diet disturbs the composition and function of the gut microbiota and generates local gut-associated and also systemic responses. Intestinal mast cells, for their part, secrete mediators which play a role in the orchestration of physiological and immunological functions of the intestine.

  17. Follistatin Alleviates Synovitis and Articular Cartilage Degeneration Induced by Carrageenan

    Directory of Open Access Journals (Sweden)

    Jun Yamada

    2014-01-01

    Full Text Available Activins are proinflammatory cytokines which belong to the TGFβ superfamily. Follistatin is an extracellular decoy receptor for activins. Since both activins and follistatin are expressed in articular cartilage, we hypothesized that activin-follistatin signaling participates in the process of joint inflammation and cartilage degeneration. To test this hypothesis, we examined the effects of follistatin in a carrageenan-induced mouse arthritis model. Synovitis induced by intra-articular injection of carrageenan was significantly alleviated by preinjection with follistatin. Macrophage infiltration into the synovial membrane was significantly reduced in the presence of follistatin. In addition, follistatin inhibited proteoglycan erosion induced by carrageenan in articular cartilage. These data indicate that activin-follistatin signaling is involved in joint inflammation and cartilage homeostasis. Our data suggest that follistatin can be a new therapeutic target for inflammation-induced articular cartilage degeneration.

  18. Butyrate alleviates metabolic impairments and protects pancreatic β cell function in pregnant mice with obesity.

    Science.gov (United States)

    Li, Hua-Ping; Chen, Xuan; Li, Ming-Qing

    2013-01-01

    The relative or absolute deficiency of pancreatic β-cell mass function underlies the pathogenesis of diabetes. It is necessary to alleviate the metabolic stress and reduce the demand for insulin to decrease the effects of mutations affecting β-cell expansion. Butyrate is a natural nutrient existed in food and can also be produced physiologically through the intestinal fermentation of fiber. Pregnancy and obesity model would be helpful for understanding how β-cell adapt to insulin resistance and how butyrate alleviate the metabolic impairment and protect pancreatic β cell function in pregnant mice with obesity. C57BL/6J female mice were divided into three groups and fed with high fat food (HF group, 40% energy from fat), high fat with sodium butyrate food (HSF group, 95% HF with 5% butyrate), or control food (CF group, 14% energy from fat), respectively. The feeding would last for 14 weeks before mating and throughout the gestation period. A subset of dams were sacrificed at gestational day (GD) 14.5 to evaluate the changes of metabolism and β-cell function, mass, proliferation and apoptosis, inflammatory reaction of islet from different diet. Pancreases were double immuno-labeled to assess the islet morphology, insulin expression, expression of proliferation gene PCNA and anti-apoptosis gene bcl-2. Moreover, we detected the expression of NF-κB, phosphorylated NF-κB (pNF-κB) to evaluate the islet inflammatory response with immunohistochemistry. Mice fed with HSF showed obviously changes including the decreased values of weight gain, glucose, insulin, triglyceride and total cholesterol level of blood compared with high fat diet group, and the reduced circulating maternal pro-inflammation factors at GD14.5. Mice fed with HF displayed β-cell hyperplasia with a greater β-cell size and β-cell area in pancreas. Furthermore, the higher ratio of apoptosis and inflammatory response were found in HF group compared with HSF and CF group, while the proliferation

  19. Type 3 innate lymphoid cells maintain intestinal epithelial stem cells after tissue damage

    NARCIS (Netherlands)

    P. Aparicio-Domingo (Patricia); M. Romera-Hernandez (Monica); J.J. Karrich (Julien J.); F.H.J. Cornelissen (Ferry); N. Papazian (Natalie); D.J. Lindenbergh-Kortleve (Dicky); J.A. Butler (James A.); L. Boon (Louis); M. Coles (Mark); J.N. Samsom (Janneke); T. Cupedo (Tom)

    2015-01-01

    textabstractDisruption of the intestinal epithelial barrier allows bacterial translocation and predisposes to destructive inflammation. To ensure proper barrier composition, crypt-residing stem cells continuously proliferate and replenish all intestinal epithelial cells within days. As a consequence

  20. Intestine transplantation

    Directory of Open Access Journals (Sweden)

    Tadeja Pintar

    2011-02-01

    Conclusion: Intestine transplantation is reserved for patients with irreversible intestinal failure due to short gut syndrome requiring total paranteral nutrition with no possibility of discontinuation and loss of venous access for patient maintenance. In these patients complications of underlying disease and long-term total parenteral nutrition are present.

  1. Alleviation of acute radiation damages by post-irradiation treatments

    International Nuclear Information System (INIS)

    Kurishita, A.; Ono, T.

    1992-01-01

    Radiation induced hematopoietic and gastro-intestinal damages in mice were tried to alleviate experimentally by post-treatment. Combined treatment of OK-432 and aztreonam clearly prevented the radiation induced sepsis and elevated the survival rate in mice; the survival was 80% in the OK-432 plus aztreonam group while it was 55% in the group treated with OK-432 alone and 0% with saline. Irsogladine maleate, an anti-ulcer drug, increased the survival rate of jejunal crypt stem cells with a clear dose-related trend. The D 0 for irsogladine maleate was 2.8 Gy although it was 2.3 Gy for saline, These findings suggest that some conventional drugs are effective for radiation induced hematopoietic and gastro-intestinal damages and the possibility that they can be applied for people exposed to radiation accidentally. (author)

  2. Lactobacillus plantarum CCFM639 alleviates aluminium toxicity.

    Science.gov (United States)

    Yu, Leilei; Zhai, Qixiao; Liu, Xiaoming; Wang, Gang; Zhang, Qiuxiang; Zhao, Jianxin; Narbad, Arjan; Zhang, Hao; Tian, Fengwei; Chen, Wei

    2016-02-01

    Aluminium (Al) is the most abundant metal in the earth's crust. Al exposure can cause a variety of adverse physiological effects in humans and animals. Our aim was to demonstrate that specific probiotic bacteria can play a special physiologically functional role in protection against Al toxicity in mice. Thirty strains of lactic acid bacteria (LAB) were tested for their aluminium-binding ability, aluminium tolerance, their antioxidative capacity, and their ability to survive the exposure to artificial gastrointestinal (GI) juices. Lactobacillus plantarum CCFM639 was selected for animal experiments because of its excellent performance in vitro. Forty mice were divided into four groups: control, Al only, Al plus CCFM639, and Al plus deferiprone (DFP). CCFM639 was administered at 10(9) CFU once daily for 10 days, followed by a single oral dose of aluminium chloride hexahydrate at 5.14 mg aluminium (LD50) for each mouse. The results showed that CCFM639 treatment led to a significant reduction in the mortality rates with corresponding decrease in intestinal aluminium absorption and in accumulation of aluminium in the tissues and amelioration of hepatic histopathological damage. This probiotic treatment also resulted in alleviation of hepatic, renal, and cerebral oxidative stress. The treatment of L. plantarum CCFM639 has potential as a therapeutic dietary strategy against acute aluminium toxicity.

  3. Dietary phenethylisothiocyanate attenuates bowel inflammation in mice

    Directory of Open Access Journals (Sweden)

    Premkumar VummidiGiridhar

    2010-04-01

    Full Text Available Abstract Background Phenethylisothiocyanate (PEITC is produced by Brassica food plants. PEO is a PEITC Essential Oil containing >95% natural PEITC. PEITC is known to produce various health benefits but its effect in alleviation of ulcerative colitis signs is unknown. Results In two efficacy studies (acute and chronic oral administration of PEO was effective at remitting acute and chronic signs of ulcerative colitis (UC in mice. Disease activity, histology and biochemical characteristics were measured in the treated animals and were compared with appropriate controls. PEO treatment significantly improved body weights and stool consistency as well as decreased intestinal bleeding. PEO treatment also reduced mucosal inflammation, depletion of goblet cells and infiltration of inflammatory cells. Attenuation of proinflammatory interleukin1β production was observed in the colons of PEO-treated animals. Expression analyses were also carried out for immune function related genes, transcription factors and cytokines in lipopolysaccharide-activated mouse macrophage cells. PEO likely affects an intricate network of immune signaling genes including a novel concentration dependent reduction of total cellular Signal Transducer and Activator of Transcription 1 (STAT1 as well as nuclear phosphorylated-STAT1 (activated form of STAT1. A PEO-concentration dependent decrease of mRNA of C-X-C motif ligand 10 (a STAT1 responsive chemokine and Interleukin 6 were also observed. Conclusions PEO might be a promising candidate to develop as a treatment for ulcerative colitis patients. The disease attenuation by PEO is likely associated with suppression of activation of STAT1 transcription and inhibition of pro-inflammatory cytokines.

  4. Modulation of Intestinal Microbiome Prevents Intestinal Ischemic Injury

    Directory of Open Access Journals (Sweden)

    Alessandra Bertacco

    2017-12-01

    Full Text Available Background: Butyrate protects against ischemic injury to the small intestine by reducing inflammation and maintaining the structure of the intestinal barrier, but is expensive, short-lived, and cannot be administered easily due to its odor. Lactate, both economical and more palatable, can be converted into butyrate by the intestinal microbiome. This study aimed to assess in a rat model whether lactate perfusion can also protect against intestinal ischemia.Materials and Methods: Rat intestinal segments were loaded in an in vitro bowel perfusion device, and water absorption or secretion was assessed based on fluorescence of FITC-inulin, a fluorescent marker bound to a biologically inert sugar. Change in FITC concentration was used as a measure of ischemic injury, given the tendency of ischemic cells to retain water. Hematoxylin and eosin-stained sections at light level microscopy were examined to evaluate intestinal epithelium morphology. Comparisons between the data sets were paired Student t-tests or ANOVA with p < 0.05 performed on GraphPad.Results: Lactate administration resulted in a protective effect against intestinal ischemia of similar magnitude to that observed with butyrate. Both exhibited approximately 1.5 times the secretion exhibited by control sections (p = 0.03. Perfusion with lactate and methoxyacetate, a specific inhibitor of lactate-butyrate conversion, abolished this effect (p = 0.09. Antibiotic treatment also eliminated this effect, rendering lactate-perfused sections similar to control sections (p = 0.72. Perfusion with butyrate and methoxyacetate did not eliminate the observed increased secretion, which indicates that ischemic protection was mediated by microbial conversion of lactate to butyrate (p = 0.71.Conclusions: Lactate's protective effect against intestinal ischemia due to microbial conversion to butyrate suggests possible applications in the transplant setting for reducing ischemic injury and ameliorating intestinal

  5. Food intolerance and mucosal inflammation.

    Science.gov (United States)

    Ohtsuka, Yoshikazu

    2015-01-01

    Most infants are immunologically active and are able to develop a tolerance to oligoclonal antigens by producing IgA, along with activation of regulatory T cells, in early infancy. Cytokines and their signaling molecules are important mediators in the intestine, regulating both oral tolerance and mucosal inflammation. This system works efficiently in most individuals, but for an as yet undefined reason, some people react to food and other proteins as though they were pathogens, with induction of chronic inflammation in the mucosa. The adverse reaction caused by ingested foods is defined as food intolerance. The clinical features of food intolerance include vomiting, diarrhea, bloody stool, eczema, failure to thrive, and a protean range of other symptoms. Intolerance can be divided into two categories depending on whether or not they are immunologically mediated. Food intolerance and mucosal inflammation are deeply related because tolerance cannot be established when there is an inflammation in the intestinal mucosa. Mast cells, eosinophils, mucosal lymphocytes, and epithelial cells are deeply involved and related to each other in the development of mucosal inflammation. Meanwhile, rectal bleeding in infancy is related to lymphoid hyperplasia with eosinophil infiltration into the colonic mucosa facilitated by C-C motif ligand 11 (CCL11, known as eotaxin-1) and C-X-C motif chemokine ligand 13 (CXCL13). Rectal bleeding in infancy may not be simply caused by allergic reactions against specific antigens, but may be due to migrated lymphocytes developing immunological tolerance; including IgA synthesizing, in the intestinal mucosa. © 2014 Japan Pediatric Society.

  6. Intestinal Ischemia

    Science.gov (United States)

    ... weight loss Intestinal ischemia Symptoms & causes Diagnosis & treatment Advertisement Mayo Clinic does not endorse companies or products. ... a Job Site Map About This Site Twitter Facebook Google YouTube Pinterest Mayo Clinic is a not- ...

  7. Intestinal Coccidia

    OpenAIRE

    MJ Ggaravi

    2007-01-01

    Intestinal Coccidia are a subclass of Apicomplexa phylum. Eucoccidida are facultative heteroxenous, but some of them are monoxenous. They have sexual and asexual life cycle. Some coccidia are human pathogens, for example: Cryptosporidium: Cryptosporidiums has many species that are mammalian intestinal parasites.C. Parvum specie is a human pathogenic protozoa. Cryptosporidum has circle or ellipse shapes and nearly 4-6 mm. It is transmitted in warm seasons. Oocyst is obtained insexual life cycl...

  8. Diversity and functions of intestinal mononuclear phagocytes

    DEFF Research Database (Denmark)

    Joeris, Thorsten; Müller-Luda, K; Agace, William Winston

    2017-01-01

    The intestinal lamina propria (LP) contains a diverse array of mononuclear phagocyte (MNP) subsets, including conventional dendritic cells (cDC), monocytes and tissue-resident macrophages (mφ) that collectively play an essential role in mucosal homeostasis, infection and inflammation. In the curr......The intestinal lamina propria (LP) contains a diverse array of mononuclear phagocyte (MNP) subsets, including conventional dendritic cells (cDC), monocytes and tissue-resident macrophages (mφ) that collectively play an essential role in mucosal homeostasis, infection and inflammation....... In the current review we discuss the function of intestinal cDC and monocyte-derived MNP, highlighting how these subsets play several non-redundant roles in the regulation of intestinal immune responses. While much remains to be learnt, recent findings also underline how the various populations of MNP adapt...

  9. Inhibition of c-Jun N-terminal Kinase Signaling Pathway Alleviates Lipopolysaccharide-induced Acute Respiratory Distress Syndrome in Rats

    Directory of Open Access Journals (Sweden)

    Jian-Bo Lai

    2016-01-01

    Conclusions: Inhibiting JNK alleviated LPS-induced acute lung inflammation and had no effects on pulmonary edema and fibrosis. JNK inhibitor might be a potential therapeutic medication in ARDS, in the context of reducing lung inflammatory.

  10. Secretion of biologically active pancreatitis-associated protein I (PAP) by genetically modified dairy Lactococcus lactis NZ9000 in the prevention of intestinal mucositis.

    Science.gov (United States)

    Carvalho, Rodrigo D; Breyner, Natalia; Menezes-Garcia, Zelia; Rodrigues, Nubia M; Lemos, Luisa; Maioli, Tatiane U; da Gloria Souza, Danielle; Carmona, Denise; de Faria, Ana M C; Langella, Philippe; Chatel, Jean-Marc; Bermúdez-Humarán, Luis G; Figueiredo, Henrique C P; Azevedo, Vasco; de Azevedo, Marcela S

    2017-02-13

    Mucositis is one of the most relevant gastrointestinal inflammatory conditions in humans, generated by the use of chemotherapy drugs, such as 5-fluoracil (5-FU). 5-FU-induced mucositis affects 80% of patients undergoing oncological treatment causing mucosal gut dysfunctions and great discomfort. As current therapy drugs presents limitations in alleviating mucositis symptoms, alternative strategies are being pursued. Recent studies have shown that the antimicrobial pancreatitis-associated protein (PAP) has a protective role in intestinal inflammatory processes. Indeed, it was demonstrated that a recombinant strain of Lactococcus lactis expressing human PAP (LL-PAP) could prevent and improve murine DNBS-induced colitis, an inflammatory bowel disease (IBD) that causes severe inflammation of the colon. Hence, in this study we sought to evaluate the protective effects of LL-PAP on 5-FU-induced experimental mucositis in BALB/c mice as a novel approach to treat the disease. Our results show that non-recombinant L. lactis NZ9000 have antagonistic activity, in vitro, against the enteroinvasive gastrointestinal pathogen L. monocytogenes and confirmed PAP inhibitory effect against Opportunistic E. faecalis. Moreover, L. lactis was able to prevent histological damage, reduce neutrophil and eosinophil infiltration and secretory Immunoglobulin-A in mice injected with 5-FU. Recombinant lactococci carrying antimicrobial PAP did not improve those markers of inflammation, although its expression was associated with villous architecture preservation and increased secretory granules density inside Paneth cells in response to 5-FU inflammation. We have demonstrated for the first time that L. lactis NZ9000 by itself, is able to prevent 5-FU-induced intestinal inflammation in BALB/c mice. Moreover, PAP delivered by recombinant L. lactis strain showed additional protective effects in mice epithelium, revealing to be a promising strategy to treat intestinal mucositis.

  11. Small Intestine Disorders

    Science.gov (United States)

    ... disease Crohn's disease Infections Intestinal cancer Intestinal obstruction Irritable bowel syndrome Ulcers, such as peptic ulcer Treatment of disorders of the small intestine depends on the cause.

  12. Intestinal Microbiota Signatures Associated With Histological Liver Steatosis in Pediatric-Onset Intestinal Failure.

    Science.gov (United States)

    Korpela, Katri; Mutanen, Annika; Salonen, Anne; Savilahti, Erkki; de Vos, Willem M; Pakarinen, Mikko P

    2017-02-01

    Intestinal failure (IF)-associated liver disease (IFALD) is the major cause of mortality in IF. The link between intestinal microbiota and IFALD is unclear. We compared intestinal microbiota of patients with IF (n = 23) with healthy controls (n = 58) using culture-independent phylogenetic microarray analysis. The microbiota was related to histological liver injury, fecal markers of intestinal inflammation, matrix metalloproteinase 9 and calprotectin, and disease characteristics. Overabundance of Lactobacilli, Proteobacteria, and Actinobacteria was observed in IF, whereas bacteria related to Clostridium clusters III, IV, and XIVa along with overall diversity and richness were reduced. Patients were segregated into 3 subgroups based on dominating bacteria: Clostridium cluster XIVa, Proteobacteria, and bacteria related to Lactobacillus plantarum. In addition to liver steatosis and fibrosis, Proteobacteria were associated with prolonged current parenteral nutrition (PN) as well as liver and intestinal inflammation. Lactobacilli were related to advanced steatosis and fibrosis mostly after weaning off PN without associated inflammation. In multivariate permutational analysis of variance, liver steatosis, bowel length, PN calories, and antibiotic treatment best explained the microbiota variation among patients with IF. Intestinal microbiota composition was associated with liver steatosis in IF and better predicted steatosis than duration of PN or length of the remaining intestine. Our results may be explained by a model in which steatosis is initiated during PN in response to proinflammatory lipopolysaccharides produced by Proteobacteria and progresses after weaning off PN, as the L plantarum group Lactobacilli becomes dominant and affects lipid metabolism by altering bile acid signaling.

  13. Alleviating energy poverty: Indian experience

    Energy Technology Data Exchange (ETDEWEB)

    Jain, Garima

    2010-09-15

    Energy services play an important role in human welfare. India faces acute energy poverty indicating lack of access of clean energy fuels. Access to electricity is limited to 56% households in India and about 89% of rural households depend on polluting energy sources. Energy poverty impacts income poverty as poor find it difficult to acquire high priced cleaner fuels. It also adversely impacts the socio economic conditions of women. The paper highlights the linkage of energy poverty with income poverty and gender inequality. It analyses measures taken to alleviate energy poverty and recommends regulatory and policy measures as way forward.

  14. Multispectral tissue characterization for intestinal anastomosis optimization

    Science.gov (United States)

    Cha, Jaepyeong; Shademan, Azad; Le, Hanh N. D.; Decker, Ryan; Kim, Peter C. W.; Kang, Jin U.; Krieger, Axel

    2015-10-01

    Intestinal anastomosis is a surgical procedure that restores bowel continuity after surgical resection to treat intestinal malignancy, inflammation, or obstruction. Despite the routine nature of intestinal anastomosis procedures, the rate of complications is high. Standard visual inspection cannot distinguish the tissue subsurface and small changes in spectral characteristics of the tissue, so existing tissue anastomosis techniques that rely on human vision to guide suturing could lead to problems such as bleeding and leakage from suturing sites. We present a proof-of-concept study using a portable multispectral imaging (MSI) platform for tissue characterization and preoperative surgical planning in intestinal anastomosis. The platform is composed of a fiber ring light-guided MSI system coupled with polarizers and image analysis software. The system is tested on ex vivo porcine intestine tissue, and we demonstrate the feasibility of identifying optimal regions for suture placement.

  15. Intestinal Ralstonia pickettii augments glucose intolerance in obesity

    DEFF Research Database (Denmark)

    Udayappan, Shanthadevi D; Kovatcheva-Datchary, Petia; Bakker, Guido J

    2017-01-01

    An altered intestinal microbiota composition has been implicated in the pathogenesis of metabolic disease including obesity and type 2 diabetes mellitus (T2DM). Low grade inflammation, potentially initiated by the intestinal microbiota, has been suggested to be a driving force in the development ...

  16. Protective effect of salvianolic acid B against intestinal ischemia ...

    African Journals Online (AJOL)

    Keywords: Salvianolic acid B, Intestinal Ischemia-reperfusion, Antioxidants, Inflammation, Intestinal ... Rats were sacrificed by cervical decapitation under pentabarbotal sodium at the dose of 50 mg/kg via i.p after IIRI induction. Blood samples were collected in a heparinized .... lipid peroxidation [17] and hence the levels of.

  17. Mechanism of leukotriene D4 inhibition of Na-alanine cotransport in intestinal epithelial cells

    OpenAIRE

    Talukder, Jamilur R.; Kekuda, Ramesh; Saha, Prosenjit; Sundaram, Uma

    2008-01-01

    In a rabbit model of chronic intestinal inflammation, we previously demonstrated inhibition of neutral Na-amino acid cotransport. The mechanism of the inhibition was secondary to a decrease in the affinity for amino acid rather than the number of cotransporters. Since leukotriene (LT)D4 is known to be elevated in enterocytes during chronic intestinal inflammation, we used rat intestinal epithelial cell (IEC-18) monolayers to determine the mechanism of regulation of Na-alanine cotransport (ala...

  18. Periarrest intestinal bacterial translocation and resuscitation outcome.

    Science.gov (United States)

    Chalkias, Athanasios; Scheetz, Marc H; Gulati, Anil; Xanthos, Theodoros

    2016-02-01

    During the periarrest period, intestinal ischemia may result in barrier dysfunction and bacterial translocation, which has clear mechanistic links to inflammation and cascade stimulation, especially in patients who are treated with therapeutic hypothermia. Despite optimal management, periarrest bacterial translocation may worsen the outcome of cardiac arrest victims. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Metabolic complications in the small intestine syndrome

    International Nuclear Information System (INIS)

    Mora, Rafael; Orozco, Reynaldo

    2000-01-01

    Metabolic complications in the syndrome of small intestine is presented in a patient of masculine sex, 27 years old, who consulted for a square of inflammation gingival, migraine, fever, anorexia and adinamia for three days, followed by maculopapular-eritematose eruption for 8 days, coincident with the ampicillin ingestion, and later on severe abdominal pain and diarrhea

  20. Curcumin Alleviates the Functional Gastrointestinal Disorders of Mice In Vivo.

    Science.gov (United States)

    Yu, Jing; Xu, Wen-Hua; Sun, Wei; Sun, Yi; Guo, Zhi-Li; Yu, Xiao-Ling

    2017-12-01

    Curcumin is a natural polyphenol extracted from the turmeric rhizome, which has a wide range of biological activities, but until now the effects of curcumin on the gastrointestinal peristalsis have not been fully understood. In vivo study, we observed the effects of curcumin on gastric emptying and intestinal propulsion rates of mice in normal state and in delayed state by atropine (ATR) or nitric oxide precursor L-arginine (L-Arg). An in vitro study explored the direct effects of curcumin on the intestinal contractility, but were studied through measuring spontaneous contraction of isolated jejunum of mice. Our results showed that intragastric administration of curcumin (200 mg/kg/day) for 10-20 days significantly improved gastric emptying and intestinal propulsion rates of mice delayed by ATR. Moreover, intragastric administration of curcumin (200 mg/kg/day) for 15 days also significantly improved mice gastric emptying and intestinal propulsion rates delayed by L-Arg. There was no significant effect on normal gastrointestinal propulsion of mice after intragastric administration of curcumin (200 mg/kg/day) for 1-20 days. When normal isolated jejunum of mice were incubated with curcumin in vitro, the amplitude of the spontaneous contractile waves of jejunum was reduced in a concentration-dependent manner. Moreover, curcumin reduced the amplitude of the contractile waves of jejunum in both contracted and relaxed state induced by acetylcholine or ATR individually. Taken together, our results suggest that curcumin has quite different effects on gastrointestinal peristalsis in vivo and in vitro. Moderate dose of curcumin by intragastric administration for more than 10 days can alleviate the functional gastrointestinal disorders of mice, but cannot affect normal gastrointestinal propulsion.

  1. Intestinal mucus accumulation in a child with acutemyeloblastic leukemia

    Directory of Open Access Journals (Sweden)

    Namık Özbek

    2009-12-01

    Full Text Available Intestinal mucus accumulation is a very rare situation observed in some solid tumors, intestinal inflammation, mucosal hyperplasia, elevated intestinal pressure, and various other diseases. However, it has never been described in acute myeloblastic leukemia. The pathogenesis of intestinal mucus accumulation is still not clear. Here, we report a 14-year-old girl with acute myeloblastic leukemia and febrile neutropenia in addition to typhlitis. She was also immobilized due to joint contractures of the lower extremities and had intestinal mucus accumulation, which was, at first, misdiagnosed as intestinal parasitosis. We speculate that typhlitis, immobilization and decreased intestinal motility due to usage of antiemetic drugs might have been the potential etiologic factors in this case. However, its impact on prognosis of the primary disease is unknown.

  2. Poverty Alleviation Programmes in Nigeria: Reflections on ...

    African Journals Online (AJOL)

    In it, we have argued that past poverty alleviation policies and programmes have been elitist and non-participatory, especially by the target population. In most cases the designs for poverty alleviations are characterized by improper conceptualization, grandiosity and lack of social justice even in implementation. Based on ...

  3. Harnessing motivation to alleviate neglect

    Directory of Open Access Journals (Sweden)

    Charlotte eRussell

    2013-06-01

    Full Text Available The syndrome of spatial neglect results from the combination of a number of deficits in attention, with patients demonstrating both spatially lateralised and non-lateralised impairments. Previous reports have hinted that there may be a motivational component to neglect and that modulating this might alleviate some of the debilitating symptoms. Additionally, recent work on the effects of reward on attention in healthy participants has revealed improvements across a number of paradigms. As the primary deficit in neglect has been associated with attention, this evidence for reward’s effects is potentially important. However, until very recently there have been few empirical studies addressing this potential therapeutic avenue. Here we review the growing body of evidence that attentional impairments in neglect can be reduced by motivation, for example in the form of preferred music or anticipated monetary reward, and discuss the implications of this for treatments for these patients. Crucially these effects of positive motivation are not observed in all patients with neglect, suggesting that the consequences of motivation may relate to individual lesion anatomy. Given the key role of dopaminergic systems in motivational processes, we suggest that motivational stimulation might act as a surrogate for dopaminergic stimulation. In addition, we consider the relationship between clinical post stroke apathy and lack of response to motivation.

  4. Intestinal pseudo-obstruction

    Science.gov (United States)

    Primary intestinal pseudo-obstruction; Acute colonic ileus; Colonic pseudo-obstruction; Idiopathic intestinal pseudo-obstruction; Ogilvie syndrome; Chronic intestinal pseudo-obstruction; Paralytic ileus - pseudo-obstruction

  5. Intestinal myiasis

    Directory of Open Access Journals (Sweden)

    U S Udgaonkar

    2012-01-01

    Full Text Available Purpose: Intestinal myiasis is a condition when the fly larvae inhabit the gastrointestinal tract and are passed out in faeces. This type of infestation results when eggs or larvae of the fly, deposited on food are inadvertently taken by man. They survive the unfavourable conditions within the gastrointestinal tract and produce disturbances, which may vary from mild to severe. The condition is not uncommon and is often misdiagnosed as pinworm infestation. Correct diagnosis by the clinical microbiologist is important to avoid unnecessary treatment. Materials and Methods: We had 7 cases of intestinal myiasis. In 2 cases the larvae were reared to adult fly in modified meat and sand medium (developed by Udgaonkar. This medium is simple and can be easily prepared in the laboratory. Results: Of the 7 larvae, 5 were Sarcophaga haemorrhoidalis, 1 Megaselia species and 1 was identified as Muscina stabulans. Conclusions: S. haemorrhoidalis was the commonest maggot involved. A high index of suspicion is required for clinical diagnosis when the patient complains of passing wriggling worms in faeces for a long period without any response to antihelminthics. The reason for long duration of illness and recurrence of infestation is baffling. The nearest to cure was colonic wash. We feel prevention is of utmost importance, which is to avoid eating food articles with easy access to flies.

  6. Inflammation and Heart Disease

    Science.gov (United States)

    ... Peripheral Artery Disease Venous Thromboembolism Aortic Aneurysm More Inflammation and Heart Disease Updated:Jun 13,2017 Understand the risks of inflammation. Although it is not proven that inflammation causes ...

  7. Nasogastric tube syndrome induced by an indwelling long intestinal tube.

    Science.gov (United States)

    Sano, Naoki; Yamamoto, Masayoshi; Nagai, Kentaro; Yamada, Keiichi; Ohkohchi, Nobuhiro

    2016-04-21

    The nasogastric tube (NGT) has become a frequently used device to alleviate gastrointestinal symptoms. Nasogastric tube syndrome (NTS) is an uncommon but potentially life-threatening complication of an indwelling NGT. NTS is characterized by acute upper airway obstruction due to bilateral vocal cord paralysis. We report a case of a 76-year-old man with NTS, induced by an indwelling long intestinal tube. He was admitted to our hospital for treatment of sigmoid colon cancer. He underwent sigmoidectomy to release a bowel obstruction, and had a long intestinal tube inserted to decompress the intestinal tract. He presented acute dyspnea following prolonged intestinal intubation, and bronchoscopy showed bilateral vocal cord paralysis. The NGT was removed immediately, and tracheotomy was performed. The patient was finally discharged in a fully recovered state. NTS be considered in patients complaining of acute upper airway obstruction, not only with a NGT inserted but also with a long intestinal tube.

  8. Puerarin alleviates neuropathic pain by inhibiting neuroinflammation in spinal cord.

    Science.gov (United States)

    Liu, Ming; Liao, Kaijun; Yu, Changxi; Li, Xuejun; Liu, Suhuan; Yang, Shuyu

    2014-01-01

    Neuropathic pain responds poorly to drug treatments, and partial relief is achieved in only about half of the patients. Puerarin, the main constituent of Puerariae Lobatae Radix, has been used extensively in China to treat hypertension and tumor. The current study examined the effects of puerarin on neuropathic pain using two most commonly used animal models: chronic constriction injury (CCI) and diabetic neuropathy. We found that consecutive intrathecal administration of puerarin (4-100 nM) for 7 days inhibited the mechanical and thermal nociceptive response induced by CCI and diabetes without interfering with the normal pain response. Meanwhile, in both models puerarin inhibited the activation of microglia and astroglia in the spinal dorsal horn. Puerarin also reduced the upregulated levels of nuclear factor-κB (NF-κB) and other proinflammatory cytokines, such as IL-6, IL-1β, and TNF-α, in the spinal cord. In summary, puerarin alleviated CCI- and diabetes-induced neuropathic pain, and its effectiveness might be due to the inhibition of neuroinflammation in the spinal cord. The anti-inflammation effect of puerarin might be related to the suppression of spinal NF-κB activation and/or cytokines upregulation. We conclude that puerarin has a significant effect on alleviating neuropathic pain and thus may serve as a therapeutic approach for neuropathic pain.

  9. Puerarin Alleviates Neuropathic Pain by Inhibiting Neuroinflammation in Spinal Cord

    Directory of Open Access Journals (Sweden)

    Ming Liu

    2014-01-01

    Full Text Available Neuropathic pain responds poorly to drug treatments, and partial relief is achieved in only about half of the patients. Puerarin, the main constituent of Puerariae Lobatae Radix, has been used extensively in China to treat hypertension and tumor. The current study examined the effects of puerarin on neuropathic pain using two most commonly used animal models: chronic constriction injury (CCI and diabetic neuropathy. We found that consecutive intrathecal administration of puerarin (4–100 nM for 7 days inhibited the mechanical and thermal nociceptive response induced by CCI and diabetes without interfering with the normal pain response. Meanwhile, in both models puerarin inhibited the activation of microglia and astroglia in the spinal dorsal horn. Puerarin also reduced the upregulated levels of nuclear factor-κB (NF-κB and other proinflammatory cytokines, such as IL-6, IL-1β, and TNF-α, in the spinal cord. In summary, puerarin alleviated CCI- and diabetes-induced neuropathic pain, and its effectiveness might be due to the inhibition of neuroinflammation in the spinal cord. The anti-inflammation effect of puerarin might be related to the suppression of spinal NF-κB activation and/or cytokines upregulation. We conclude that puerarin has a significant effect on alleviating neuropathic pain and thus may serve as a therapeutic approach for neuropathic pain.

  10. Intestinal Failure (Short Bowel Syndrome)

    Science.gov (United States)

    Intestinal Failure (Short Bowel Syndrome) What is intestinal failure? Intestinal failure occurs when a significant portion of the small ... intestine does. Who is at risk for intestinal failure? N Babies (usually premature) who have had surgery ...

  11. Farewell to Animal Testing: Innovations on Human Intestinal Microphysiological Systems

    Directory of Open Access Journals (Sweden)

    Tae Hyun Kang

    2016-06-01

    Full Text Available The human intestine is a dynamic organ where the complex host-microbe interactions that orchestrate intestinal homeostasis occur. Major contributing factors associated with intestinal health and diseases include metabolically-active gut microbiota, intestinal epithelium, immune components, and rhythmical bowel movement known as peristalsis. Human intestinal disease models have been developed; however, a considerable number of existing models often fail to reproducibly predict human intestinal pathophysiology in response to biological and chemical perturbations or clinical interventions. Intestinal organoid models have provided promising cytodifferentiation and regeneration, but the lack of luminal flow and physical bowel movements seriously hamper mimicking complex host-microbe crosstalk. Here, we discuss recent advances of human intestinal microphysiological systems, such as the biomimetic human “Gut-on-a-Chip” that can employ key intestinal components, such as villus epithelium, gut microbiota, and immune components under peristalsis-like motions and flow, to reconstitute the transmural 3D lumen-capillary tissue interface. By encompassing cutting-edge tools in microfluidics, tissue engineering, and clinical microbiology, gut-on-a-chip has been leveraged not only to recapitulate organ-level intestinal functions, but also emulate the pathophysiology of intestinal disorders, such as chronic inflammation. Finally, we provide potential perspectives of the next generation microphysiological systems as a personalized platform to validate the efficacy, safety, metabolism, and therapeutic responses of new drug compounds in the preclinical stage.

  12. Mucosal T cells in gut homeostasis and inflammation

    OpenAIRE

    van Wijk, Femke; Cheroutre, Hilde

    2010-01-01

    The antigen-rich environment of the gut interacts with a highly integrated and specialized mucosal immune system that has the challenging task of preventing invasion and the systemic spread of microbes, while avoiding excessive or unnecessary immune responses to innocuous antigens. Disruption of the mucosal barrier and/or defects in gut immune regulatory networks may lead to chronic intestinal inflammation as seen in inflammatory bowel disease. The T-cell populations of the intestine play a c...

  13. Enteric Virome Sensing-Its Role in Intestinal Homeostasis and Immunity.

    Science.gov (United States)

    Metzger, Rebecca N; Krug, Anne B; Eisenächer, Katharina

    2018-03-23

    Pattern recognition receptors (PRRs) sensing commensal microorganisms in the intestine induce tightly controlled tonic signaling in the intestinal mucosa, which is required to maintain intestinal barrier integrity and immune homeostasis. At the same time, PRR signaling pathways rapidly trigger the innate immune defense against invasive pathogens in the intestine. Intestinal epithelial cells and mononuclear phagocytes in the intestine and the gut-associated lymphoid tissues are critically involved in sensing components of the microbiome and regulating immune responses in the intestine to sustain immune tolerance against harmless antigens and to prevent inflammation. These processes have been mostly investigated in the context of the bacterial components of the microbiome so far. The impact of viruses residing in the intestine and the virus sensors, which are activated by these enteric viruses, on intestinal homeostasis and inflammation is just beginning to be unraveled. In this review, we will summarize recent findings indicating an important role of the enteric virome for intestinal homeostasis as well as pathology when the immune system fails to control the enteric virome. We will provide an overview of the virus sensors and signaling pathways, operative in the intestine and the mononuclear phagocyte subsets, which can sense viruses and shape the intestinal immune response. We will discuss how these might interact with resident enteric viruses directly or in context with the bacterial microbiome to affect intestinal homeostasis.

  14. Enteric Virome Sensing—Its Role in Intestinal Homeostasis and Immunity

    Directory of Open Access Journals (Sweden)

    Rebecca N. Metzger

    2018-03-01

    Full Text Available Pattern recognition receptors (PRRs sensing commensal microorganisms in the intestine induce tightly controlled tonic signaling in the intestinal mucosa, which is required to maintain intestinal barrier integrity and immune homeostasis. At the same time, PRR signaling pathways rapidly trigger the innate immune defense against invasive pathogens in the intestine. Intestinal epithelial cells and mononuclear phagocytes in the intestine and the gut-associated lymphoid tissues are critically involved in sensing components of the microbiome and regulating immune responses in the intestine to sustain immune tolerance against harmless antigens and to prevent inflammation. These processes have been mostly investigated in the context of the bacterial components of the microbiome so far. The impact of viruses residing in the intestine and the virus sensors, which are activated by these enteric viruses, on intestinal homeostasis and inflammation is just beginning to be unraveled. In this review, we will summarize recent findings indicating an important role of the enteric virome for intestinal homeostasis as well as pathology when the immune system fails to control the enteric virome. We will provide an overview of the virus sensors and signaling pathways, operative in the intestine and the mononuclear phagocyte subsets, which can sense viruses and shape the intestinal immune response. We will discuss how these might interact with resident enteric viruses directly or in context with the bacterial microbiome to affect intestinal homeostasis.

  15. Interactions between the intestinal microbiome and liver diseases.

    Science.gov (United States)

    Schnabl, Bernd; Brenner, David A

    2014-05-01

    The human intestine harbors a diverse community of microbes that promote metabolism and digestion in their symbiotic relationship with the host. Disturbance of its homeostasis can result in disease. We review factors that disrupt intestinal homeostasis and contribute to nonalcoholic fatty liver disease, steatohepatitis, alcoholic liver disease, and cirrhosis. Liver disease has long been associated with qualitative and quantitative (overgrowth) dysbiotic changes in the intestinal microbiota. Extrinsic factors, such as the Western diet and alcohol, contribute to these changes. Dysbiosis results in intestinal inflammation, a breakdown of the intestinal barrier, and translocation of microbial products in animal models. However, the contribution of the intestinal microbiome to liver disease goes beyond simple translocation of bacterial products that promote hepatic injury and inflammation. Microbial metabolites produced in a dysbiotic intestinal environment and host factors are equally important in the pathogenesis of liver disease. We review how the combination of liver insult and disruptions in intestinal homeostasis contribute to liver disease. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

  16. NITRIC OXIDE INTERFERES WITH HYPOXIA SIGNALING DURING COLONIC INFLAMMATION

    OpenAIRE

    CARIA,Cintia Rabelo e Paiva; MOSCATO,Camila Henrique; TOMÉ,Renata Bortolin Guerra; PEDRAZZOLI Jr,José; RIBEIRO,Marcelo Lima; GAMBERO,Alessandra

    2014-01-01

    Context Intestinal inflammation can induce a local reduction in oxygen levels that triggers an adaptive response centered on the expression of hypoxia-inducible factors (HIFs). Nitric oxide, a well-described inflammatory mediator, may interfere with hypoxia signaling. Objectives We aimed to evaluate the role of nitric oxide in hypoxia signaling during colonic inflammation. Methods Colitis was induced by single (acute) or repeated (reactivated colitis) trinitrobenzenosulfonic acid administ...

  17. PARP-1 inhibition alleviates diabetic cardiac complications in experimental animals.

    Science.gov (United States)

    Zakaria, Esraa M; El-Bassossy, Hany M; El-Maraghy, Nabila N; Ahmed, Ahmed F; Ali, Abdelmoneim A

    2016-11-15

    Cardiovascular complications are the major causes of mortality among diabetic population. Poly(ADP-ribose) polymerase-1 enzyme (PARP-1) is activated by oxidative stress leading to cellular damage. We investigated the implication of PARP-1 in diabetic cardiac complications. Type 2 diabetes was induced in rats by high fructose-high fat diet and low streptozotocin dose. PARP inhibitor 4-aminobenzamide (4-AB) was administered daily for ten weeks after diabetes induction. At the end of study, surface ECG, blood pressure and vascular reactivity were studied. PARP-1 activity, reduced glutathione (GSH) and nitrite contents were assessed in heart muscle. Fasting glucose, fructosamine, insulin, and tumor necrosis factor alpha (TNF-α) levels were measured in serum. Finally, histological examination and collagen deposition detection in rat ventricular and aortic sections were carried out. Hearts isolated from diabetic animals showed increased PARP-1 enzyme activity compared to control animals while significantly reduced by 4-AB administration. PARP-1 inhibition by 4-AB alleviated cardiac ischemia in diabetic animals as indicated by ECG changes. PARP-1 inhibition also reduced cardiac inflammation in diabetic animals as evidenced by histopathological changes. In addition, 4-AB administration improved the elevated blood pressure and the associated exaggerated vascular contractility, endothelial destruction and vascular inflammation seen in diabetic animals. Moreover, PARP-1 inhibition decreased serum levels of TNF-α and cardiac nitrite but increased cardiac GSH contents in diabetic animals. However, PARP-1 inhibition did not significantly affect the developed hyperglycemia. Our findings prove that PARP-1 enzyme plays an important role in diabetic cardiac complications through combining inflammation, oxidative stress, and fibrosis mechanisms. Copyright © 2016. Published by Elsevier B.V.

  18. Innate Immune Activation in Intestinal Homeostasis

    OpenAIRE

    Harrison, Oliver J.; Maloy, Kevin J.

    2011-01-01

    Loss of intestinal immune regulation leading to aberrant immune responses to the commensal microbiota are believed to precipitate the chronic inflammation observed in the gastrointestinal tract of patients with inflammatory bowel diseases (IBD), Crohn's disease and ulcerative colitis. Innate immune receptors that recognize conserved components derived from the microbiota are widely expressed by both epithelial cells and leucocytes of the gastrointestinal tract and play a key role in host prot...

  19. Intestinal Leiomyositis: A Cause of Chronic Intestinal Pseudo-Obstruction in 6 Dogs.

    Science.gov (United States)

    Zacuto, A C; Pesavento, P A; Hill, S; McAlister, A; Rosenthal, K; Cherbinsky, O; Marks, S L

    2016-01-01

    Intestinal leiomyositis is a suspected autoimmune disorder affecting the muscularis propria layer of the gastrointestinal tract and is a cause of chronic intestinal pseudo-obstruction in humans and animals. To characterize the clinical presentation, histopathologic features, and outcome of dogs with intestinal leiomyositis in an effort to optimize treatment and prognosis. Six client-owned dogs. Retrospective case series. Medical records were reviewed to describe signalment, clinicopathologic and imaging findings, histopathologic diagnoses, treatment, and outcome. All biopsy specimens were reviewed by a board-certified pathologist. Median age of dogs was 5.4 years (range, 15 months-9 years). Consistent clinical signs included vomiting (6/6), regurgitation (2/6), and small bowel diarrhea (3/6). Median duration of clinical signs before presentation was 13 days (range, 5-150 days). Diagnostic imaging showed marked gastric distension with dilated small intestines in 4/6 dogs. Full-thickness intestinal biopsies were obtained in all dogs by laparotomy. Histopathology of the stomach and intestines disclosed mononuclear inflammation, myofiber degeneration and necrosis, and fibrosis centered within the region of myofiber loss in the intestinal muscularis propria. All dogs received various combinations of immunomodulatory and prokinetic treatment, antimicrobial agents, antiemetics, and IV fluids, but none of the dogs showed a clinically relevant improvement with treatment. Median survival was 19 days after diagnosis (range, 3-270 days). Intestinal leiomyositis is a cause of intestinal pseudo-obstruction and must be diagnosed by full-thickness intestinal biopsy. This disease should be considered in dogs with acute and chronic vomiting, regurgitation, and small bowel diarrhea. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  20. Increased intestinal marker absorption due to regional permeability changes and decreased intestinal transit during sepsis in the rat

    International Nuclear Information System (INIS)

    Wang, Q.; Pantzar, N.; Jeppson, B.; Westroem, B.R.; Karlsson, B.W.

    1994-01-01

    The intestinal barrier properties are impaired during inflammation and sepsis, but the mechanisms behind this are unknown and were therefore investigated during experimental sepsis in rats. The different-sized intestinal absorption markers 51 Cr-labeled ethylenediaminetetraacetic acid (EDTA) and ovalbumin were gavaged to rats made septic by intra-abdominal bacterial implantation and to sham-operated rats. Regional tissue permeability was measured in diffusion chambers, and intestinal transit was evaluated by intestinal accumulation of gavaged 51 Cr-EDTA. In comparison with the sham-operated rats, septic rats had higher 51 Cr-EDTA levels in blood and urine and showed a prolonged intestinal transit. Septic rats also had a lower tissue permeability to both markers in the small intestines but higher permeability to ovalbumin in the colon. Rats receiving morphine to decrease intestinal motility showed similar changes, with a decreased intestinal transit and increased marker absorption. Thr results suggest that the increased intestinal absorption during sepsis was due to regional permeability changes and prolonged intestinal transit. 38 refs., 4 figs., 2 tabs

  1. Intestinal, extra-intestinal and systemic sequelae of Toxoplasma gondii induced acute ileitis in mice harboring a human gut microbiota.

    Directory of Open Access Journals (Sweden)

    Eliane von Klitzing

    acute ileitis following peroral high dose T. gondii infection. Thus, hma mice constitute a suitable model to further dissect the interactions between pathogens, human microbiota and vertebrate host immunity during acute intestinal inflammation.

  2. Intestinal alkaline phosphatase: novel functions and protective effects.

    Science.gov (United States)

    Lallès, Jean-Paul

    2014-02-01

    Important protective roles of intestinal alkaline phosphatase (IAP)--including regulation of intestinal surface pH, absorption of lipids, detoxification of free nucleotides and bacterial lipopolysaccharide, attenuation of intestinal inflammation, and possible modulation of the gut microbiota--have been reviewed recently. IAP is modulated by numerous nutritional factors. The present review highlights new findings on the properties of IAP and extends the list of its protective functions. Critical assessment of data suggests that some IAP properties are a direct result of dephosphorylation of proinflammatory moieties, while others (e.g., gut barrier protection and microbiota shaping) may be secondary to IAP-mediated downregulation of inflammation. IAP and tissue-nonspecific alkaline phosphatase isoforms characterize the small intestine and the colon, respectively. Gastrointestinal administration of exogenous IAP ameliorates gut inflammation and favors gut tissue regeneration, whereas enteral and systemic IAP administration attenuates systemic inflammation only. Finally, the IAP gene family has a strong evolutionary link to food-driven changes in gastrointestinal tract anatomy and microbiota composition. Therefore, stimulation of IAP activity by dietary intervention is a goal for preserving gut homeostasis and health by minimizing low-grade inflammation. © 2013 International Life Sciences Institute.

  3. High amylose resistant starch diet ameliorates oxidative stress, inflammation, and progression of chronic kidney disease

    Science.gov (United States)

    Inflammation is a major mediator of CKD progression and is partly driven by altered gut microbiome and intestinal barrier disruption, events which are caused by: urea influx in the intestine resulting in dominance of urease-possessing bacteria; disruption of epithelial barrier by urea-derived ammoni...

  4. A resistant starch fiber diet ameliorates oxidative stress, inflammation, and progression of chronic kidney disease (CKD)

    Science.gov (United States)

    Inflammation is a constant feature and a major mediator of CKD progression. It is, in part, driven by altered gut microbiome and disruption of intestinal epithelial barrier, events which are primarily caused by: 1- urea influx in the intestine resulting in dominance of urease-possessing bacteria; 2-...

  5. Neuropeptide Y (NPY) promotes inflammation-induced tumorigenesis by enhancing epithelial cell proliferation.

    Science.gov (United States)

    Jeppsson, Sabrina; Srinivasan, Shanthi; Chandrasekharan, Bindu

    2017-02-01

    We have demonstrated that neuropeptide Y (NPY), abundantly produced by enteric neurons, is an important regulator of intestinal inflammation. However, the role of NPY in the progression of chronic inflammation to tumorigenesis is unknown. We investigated whether NPY could modulate epithelial cell proliferation and apoptosis, and thus regulate tumorigenesis. Repeated cycles of dextran sodium sulfate (DSS) were used to model inflammation-induced tumorigenesis in wild-type (WT) and NPY knockout (NPY -/- ) mice. Intestinal epithelial cell lines (T84) were used to assess the effects of NPY (0.1 µM) on epithelial proliferation and apoptosis in vitro. DSS-WT mice exhibited enhanced intestinal inflammation, polyp size, and polyp number (7.5 ± 0.8) compared with DSS-NPY -/- mice (4 ± 0.5, P inflammation-induced tumorigenesis by NPY-epithelial cross talk as mediated by activation of PI3-K signaling and downregulation of miR-375. Our work exemplifies a novel role of neuropeptide Y (NPY) in regulating inflammation-induced tumorigenesis via two modalities: first by enhanced proliferation (PI3-K/pAkt), and second by downregulation of microRNA-375 (miR-375)-dependent apoptosis in intestinal epithelial cells. Our data establish the existence of a microRNA-mediated cross talk between enteric neurons producing NPY and intestinal epithelial cells, and the potential of neuropeptide-regulated miRNAs as potential therapeutic molecules for the management of inflammation-associated tumors in the gut.

  6. Non-Meckel Small Intestine Diverticulitis

    Directory of Open Access Journals (Sweden)

    Shamim Ejaz

    2017-08-01

    Full Text Available Non-Meckel small intestine diverticulitis can have many manifestations and its management is not well-defined. We report 4 unselect cases of small intestine diverticulitis; all patients were seen by the same physician at the Emergency Center at The University of Texas MD Anderson Cancer Center between 1999 and 2014. The median age at diagnosis of these patients was 82 years (range, 76–87 years. All 4 patients presented with acute onset of abdominal pain, and computed tomography scans showed characteristics of small intestine diverticulitis unrelated to cancer. Most of the diverticula were found in the region of the duodenum and jejuno-ileal segments of the small intestine. The patients, even those with peripancreatic inflammation and localized perforation, were treated conservatively. Non-Meckel diverticulitis can be overlooked in the initial diagnosis because of the location of the diverticulosis, the age of the patient, and the rarity of the disease. Because patients with non-Meckel small intestine diverticulitis can present with acute abdominal pain, non-Meckel small intestine diverticulitis should be considered in the differential diagnosis of patients with acute abdominal pain, and computed tomography scans can help identify the condition. Because of the rarity of non-Meckel small intestine diverticulitis, few studies have been published, and the data are inconclusive about how best to approach these patients. Our experience with these 4 elderly patients indicates that non-Meckel small intestine diverticulitis can be treated conservatively, which avoids the potential morbidity and mortality of a surgical approach.

  7. Sirtuin 2 Regulates Microvascular Inflammation during Sepsis

    Directory of Open Access Journals (Sweden)

    Nancy Buechler

    2017-01-01

    Full Text Available Objective. Sepsis and septic shock, the leading causes of death in noncoronary intensive care units, kill more than 200,000/year in the US alone. Circulating cell-endothelial cell interactions are the rate determining factor in sepsis inflammation. Sirtuin, a seven-member family of proteins (SIRT1–7, epigenetically controls inflammation. We have studied the roles of SIRTs 1, 3, and 6 in sepsis previously. In this project, we studied the role of SIRT2 on sepsis-related inflammation. Methods. Sepsis was induced in C57Bl/6 (WT, SIRT2 knockout (SIRT2KO, and SIRT2 overexpressing (SIRT2KI mice by cecal ligation and puncture (CLP. We studied leukocyte/platelet adhesion using intravital microscopy and E-selectin/ICAM-1 adhesion molecule expression in the small intestine with immunohistochemistry (IHC six hours post-CLP/sham surgery. We also studied 7-day survival rates in WT, SIRT2KO, and SIRT2KI sepsis mice. Results. Compared to WT mice, SIRT2KO mice show exaggeration while SIRT2KI mice show attenuation of cellular adhesion with sepsis in the small intestine. We also show that the small intestinal E-selectin and ICAM-1 expressions increased in SIRT2KO and decreased in SIRT2KI mice versus those in WT sepsis mice. We show that the 7-day survival rate is decreased in SIRT2KO and increased in SIRT2KI sepsis mice. Conclusion. SIRT2 modulates microvascular inflammation in sepsis and affects survival.

  8. Inflammation of the Orbit

    Science.gov (United States)

    ... Glaucoma (Video) Macular Degeneration Additional Content Medical News Inflammation of the Orbit (Inflammatory Orbital Pseudotumor) By James ... Introduction to Eye Socket Disorders Cavernous Sinus Thrombosis Inflammation of the Orbit Orbital Cellulitis Preseptal Cellulitis Tumors ...

  9. Inflammation and coagulation

    NARCIS (Netherlands)

    Levi, Marcel; van der Poll, Tom

    2010-01-01

    In the pathogenesis of sepsis, inflammation and coagulation play a pivotal role. Increasing evidence points to an extensive cross-talk between these two systems, whereby inflammation leads to activation of coagulation, and coagulation also considerably affects inflammatory activity. Molecular

  10. Intestinal microbiome landscaping

    NARCIS (Netherlands)

    Shetty, Sudarshan A.; Hugenholtz, Floor; Lahti, Leo; Smidt, Hauke; Vos, de Willem M.

    2017-01-01

    High individuality, large complexity and limited understanding of the mechanisms underlying human intestinal microbiome function remain the major challenges for designing beneficial modulation strategies. Exemplified by the analysis of intestinal bacteria in a thousand Western adults, we discuss

  11. Hypoxia and Inactivity Related Physiological Changes (Constipation, Inflammation Are Not Reflected at the Level of Gut Metabolites and Butyrate Producing Microbial Community: The PlanHab Study

    Directory of Open Access Journals (Sweden)

    Robert Šket

    2017-05-01

    the developed symptoms of low magnitude obesity-related syndromes was primarily driven by the onset of inactivity (lack of exercise in NBR that were exacerbated by systemic hypoxia (HBR and significantly alleviated by exercise, despite hypoxia (HAmb. Butyrate producing community in colon exhibited apparent resilience toward short-term modifications in host exercise or hypoxia. Progressive constipation (decreased intestinal motility and increased local inflammation marker suggest that changes in microbial colonization and metabolism were taking place at the location of small intestine.

  12. Alleviating Poverty Through Vocational Education: The Nigerian ...

    African Journals Online (AJOL)

    The paper concludes that well-articulated vocational education policy and programmes will assist in employment generations and poverty reduction in Nigeria. Keywords: Alleviating Poverty, Vocational Education, Nigerian Experience Journal of Technology and Education in Nigeria Vol. 10 (2) 2005: pp. 10-14 ...

  13. Chinese herbal medicine alleviating hyperandrogenism of PCOS ...

    African Journals Online (AJOL)

    Background: Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder in women hence Chinese herbal medicine (CHM) has been chosen by many clinicians and patients as alternative treatment for PCOS. The present study was to explore the effects of CHM in alleviating hyperandrogenism of PCOS ...

  14. ACHIEVING POVERTY ALLEVIATION IN NIGERIA THROUGH ...

    African Journals Online (AJOL)

    ... and the inconsistent financial policies of the Nigerian financial system. The paper concludes that the mortgage market in the country could be strengthened to act as an instrument for poverty alleviation and economic empowerment. It recommends the introduction of pro-poor mortgage facilities in the mortgage industry in ...

  15. Maintenance of a healthy trajectory of the intestinal microbiome during aging: A dietary approach

    NARCIS (Netherlands)

    Candela, M.; Biagi, E.; Brigidi, P.; O'Toole, P.W.; Vos, de W.M.

    2014-01-01

    Sharing an intense transgenomic metabolism with the host, the intestinal microbiota is an essential factor for several aspects of the human physiology. However, several age-related factors, such as changes diet, lifestyle, inflammation and frailty, force the deterioration of this intestinal

  16. Small Intestine Cancer Treatment

    Science.gov (United States)

    ... all of an organ that contains cancer. The resection may include the small intestine and nearby organs (if the cancer has spread). The doctor may remove the section of the small intestine that contains cancer and perform an anastomosis (joining the cut ends of the intestine together). ...

  17. The Relationship Among Perceived Stress, Symptoms, and Inflammation in Persons With Inflammatory Bowel Disease.

    Science.gov (United States)

    Targownik, Laura E; Sexton, Kathryn A; Bernstein, Matthew T; Beatie, Brooke; Sargent, Michael; Walker, John R; Graff, Lesley A

    2015-07-01

    Previous studies have demonstrated that stress is associated with increased disease activity in individuals with inflammatory bowel disease (IBD). The association between perceived stress and gastrointestinal inflammation is not well described. Participants were recruited from a population-based registry of individuals with known IBD. Symptomatic disease activity was assessed using validated clinical indices: the Manitoba IBD Index (MIBDI) and Harvey Bradshaw Index (HBI) for Crohn's disease (CD), and Powell Tuck Index (PTI) for ulcerative colitis (UC). Perceived stress was measured using Cohen's Perceived Stress Scale (CPSS). Intestinal inflammation was determined through measurement of fecal calprotectin (FCAL), with a level exceeding 250 μg/g indicating significant inflammation. Logistic regressions were used to evaluate the association between intestinal inflammation, perceived stress, and disease activity. Of the 478 participants with completed surveys and stool samples, perceived stress was associated with symptomatic activity (MIBDI) for both CD and UC (1.07 per 1-point increase on the CPSS, 95% confidence interval (CI) 1.03-1.10 and 1.03-1.11, respectively). There was no significant association between perceived stress and intestinal inflammation for either CD or UC. Active symptoms (MIBDI ≤3) were associated with intestinal inflammation in UC (odds ratio (OR) 3.94, 95% CI 1.65-9.43), but not in CD (OR 0.98, 95% CI 0.51-1.88). Symptomatic disease activity was unrelated to intestinal inflammation in CD and only weakly associated in UC. Although there was a strong relationship between perceived stress and gastrointestinal symptoms, perceived stress was unrelated to concurrent intestinal inflammation. Longitudinal investigation is required to determine the directionality of the relationship between perceived stress, inflammation, and symptoms in IBD.

  18. From inflammation to cancer.

    Science.gov (United States)

    Korniluk, A; Koper, O; Kemona, H; Dymicka-Piekarska, V

    2017-02-01

    The participation of inflammation in the progression of cancer for many years have been the subject of research. In the 19th century, there was evidence that an acute inflammation may inhibit the development of cancer. However, chronic inflammation affects the progression of the disease. Today, it is known that inflammation and cancer use similar mechanisms of development such as severe cell proliferation or angiogenesis. It has been shown that prolonged presence of inflammatory cells and factors in the tumor microenvironment can accelerate its growth and inhibit apoptosis of transformed cells. In this article we present a brief history of the discovery mechanisms and potential links between acute and chronic inflammation and cancer.

  19. Emodin alleviates bleomycin-induced pulmonary fibrosis in rats.

    Science.gov (United States)

    Guan, Ruijuan; Zhao, Xiaomei; Wang, Xia; Song, Nana; Guo, Yuhong; Yan, Xianxia; Jiang, Liping; Cheng, Wenjing; Shen, Linlin

    2016-11-16

    Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease with few treatment options and poor prognosis. Emodin, extracted from Chinese rhubarb, was found to be able to alleviate bleomycin (BLM)-induced pulmonary fibrosis, yet the underlying mechanism remains largely unknown. This study aimed to further investigate the effects of emodin on the inflammation and fibrosis of BLM-induced pulmonary fibrosis and the mechanism involved in rats. Our results showed that emodin improved pulmonary function, reduced weight loss and prevented death in BLM-treated rats. Emodin significantly relieved lung edema and fibrotic changes, decreased collagen deposition, and suppressed the infiltration of myofibroblasts [characterized by expression of α-smooth muscle actin (α-SMA)] and inflammatory cells (mainly macrophages and lymphocytes). Moreover, emodin reduced levels of TNF-α, IL-6, TGF-β1 and heat shock protein (HSP)-47 in the lungs of BLM-treated rats. In vitro, emodin profoundly inhibited TGF-β1-induced α-SMA, collagen IV and fibronectin expression in human embryo lung fibroblasts (HELFs). Emodin also inhibited TGF-β1-induced Smad2/3 and STAT3 activation, indicating that Smad2/3 and STAT3 inactivation mediates emodin-induced effects on TGF-β1-induced myofibroblast differentiation. These results suggest that emodin can exert its anti-fibrotic effect via suppression of TGF-β1 signaling and subsequently inhibition of inflammation, HSP-47 expression, myofibroblast differentiation and extracellular matrix (ECM) deposition. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  20. Changes in intestinal microbiota composition and metabolism coincide with increased intestinal permeability in young adults under prolonged physiological stress.

    Science.gov (United States)

    Karl, J Philip; Margolis, Lee M; Madslien, Elisabeth H; Murphy, Nancy E; Castellani, John W; Gundersen, Yngvar; Hoke, Allison V; Levangie, Michael W; Kumar, Raina; Chakraborty, Nabarun; Gautam, Aarti; Hammamieh, Rasha; Martini, Svein; Montain, Scott J; Pasiakos, Stefan M

    2017-06-01

    The magnitude, temporal dynamics, and physiological effects of intestinal microbiome responses to physiological stress are poorly characterized. This study used a systems biology approach and a multiple-stressor military training environment to determine the effects of physiological stress on intestinal microbiota composition and metabolic activity, as well as intestinal permeability (IP). Soldiers ( n = 73) were provided three rations per day with or without protein- or carbohydrate-based supplements during a 4-day cross-country ski-march (STRESS). IP was measured before and during STRESS. Blood and stool samples were collected before and after STRESS to measure inflammation, stool microbiota, and stool and plasma global metabolite profiles. IP increased 62 ± 57% (mean ± SD, P Intestinal microbiota responses were characterized by increased α-diversity and changes in the relative abundance of >50% of identified genera, including increased abundance of less dominant taxa at the expense of more dominant taxa such as Bacteroides Changes in intestinal microbiota composition were linked to 23% of metabolites that were significantly altered in stool after STRESS. Together, pre-STRESS Actinobacteria relative abundance and changes in serum IL-6 and stool cysteine concentrations accounted for 84% of the variability in the change in IP. Findings demonstrate that a multiple-stressor military training environment induced increases in IP that were associated with alterations in markers of inflammation and with intestinal microbiota composition and metabolism. Associations between IP, the pre-STRESS microbiota, and microbiota metabolites suggest that targeting the intestinal microbiota could provide novel strategies for preserving IP during physiological stress. NEW & NOTEWORTHY Military training, a unique model for studying temporal dynamics of intestinal barrier and intestinal microbiota responses to stress, resulted in increased intestinal permeability concomitant with

  1. The friendly bacteria within us Commensal bacteria of the intestine ...

    Indian Academy of Sciences (India)

    Short chain fatty acids (SCFA) are main source of energy for colonic epithelial cells · SCFA – role in colonic disease · SCFA prevent mucosal inflammation · Immunoregulation by gut bacteria · Balance of bacterial species in the gut · Immunosensory detection of intestinal bacteria · Pathogenic bacteria release interleukin-8 ...

  2. (neutrophil) Activity, Chronic Gastritis, Gastric Atrophy And Intestinal ...

    African Journals Online (AJOL)

    Incidental (early gastric) cancer was found in 3%, dysplasia in 2% and reactive gastropathy in 7% of the cases. A statistically significant relationship was found between Helicobacter pylori colonization intensity and the degrees of neutrophil activity, chronic inflammation and intestinal metaplasia. Conclusion: We concluded ...

  3. poverty and poverty alleviation in globalised cities

    OpenAIRE

    Verena Ast

    2014-01-01

    In the light of increasing "division of the cities" and its underlying process of socio-spatial segregation researches focus more and more on the consequences of this process: the development of advantaged and disadvantaged districts within contemporary cities. Thereby especially poverty alleviation respectively poverty eradication in disadvantaged districts becomes an emerging and central field of intervention in social policies. This is due to the broad impact of poverty like higher risk of...

  4. Integration of family planning with poverty alleviation.

    Science.gov (United States)

    Peng, P

    1996-12-01

    The Chinese Communist Central Committee and the State Council aim to solve food and clothing problems among impoverished rural people by the year 2000. This goal was a priority on the agenda of the recent October 1996 National Conference on Poverty Alleviation and Development and the 1996 National Conference of the State Family Planning Commission. Poverty is attributed to rapid population growth and underdevelopment. Poverty is concentrated in parts of 18 large provinces. These provinces are characterized by Family Planning Minister Peng as having high birth rates, early marriage and childbearing, unplanned births, and multiple births. Overpopulation is tied to overconsumption, depletion of resources, deforestation, soil erosion, pollution, shortages of water, decreases in shares of cultivated land, degraded grasslands, and general destruction of the environment. Illiteracy in poor areas is over 20%, compared to the national average of 15%. Mortality and morbidity are higher. Family planning is harder to enforce in poor areas. Pilot programs in Sichuan and Guizhou provinces are promoting integration of family planning with poverty alleviation. Several conferences have addressed the integrated program strategies. Experience has shown that poverty alleviation occurs by controlled population growth and improved quality of life. Departments should "consolidate" their development efforts under Communist Party leadership at all levels. Approaches should emphasize self-reliance and public mobilization. The emphasis should be on women's participation in development. Women's income should be increased. Family planning networks at the grassroots level need to be strengthened simultaneously with increased poverty alleviation and development. The government strategy is to strengthen leadership, mobilize the public, and implement integrated programs.

  5. [Effect of Pentavac and MMR vaccination on the intestine.].

    Science.gov (United States)

    Thornjóðleifsson, Bjarni; Davíðsdóttir, Katrín; Agnarsson, Ulfur; Theodórs, Arndís; Gunnarsdóttir, Aðalbjœrg; Mœller, Elva; Jónsdóttir, Auður; Sigþórsson, Guðmundur; Kjeld, Matthías; Bjarnason, Ingvar

    2002-06-01

    The safety of infant vaccination has been questioned in recent years. In particular it has been suggested that the measles, mumps and rubella (MMR) vaccination leads to brain damage manifesting as autism consequent to the development of an "enterocolitis" in the immediate post-vaccination period. To assess if MMR vaccination is associated with sub-clinical intestinal inflammation which is central to the autistic "enterocolitis" theory. The study was not designed to test directly the association of autism to MMR vaccination. We studied 109/20 infants, before and two and four weeks after immunization with Pentavac and MMR vaccines, for the presence of intestinal inflammation (faecal calprotectin). Neither vaccination was associated with any significant increase in faecal calprotectin concentrations. The failure of the MMR vaccination to cause an intestinal inflammatory response provides evidence against the proposed gut-brain interaction that is central to the autistic "enterocolitis" hypothesis.

  6. Potential of Lactobacillus plantarum CCFM639 in Protecting against Aluminum Toxicity Mediated by Intestinal Barrier Function and Oxidative Stress.

    Science.gov (United States)

    Yu, Leilei; Zhai, Qixiao; Tian, Fengwei; Liu, Xiaoming; Wang, Gang; Zhao, Jianxin; Zhang, Hao; Narbad, Arjan; Chen, Wei

    2016-12-02

    Aluminum (Al) is a ubiquitous metal that can seriously harm the health of animals and humans. In our previous study, we demonstrated that Lactobacillus plantarum CCFM639 can decrease Al burden in the tissues of mice by inhibiting intestinal Al absorption. The main aim of the present research was to investigate whether the protection by the strain is also associated with enhancement of the intestinal barrier, alleviation of oxidative stress and modulation of the inflammatory response. In an in vitro cell model, two protection modes (intervention and therapy) were examined and the results indicated that L. plantarum CCFM639 alleviated Al-induced cytotoxicity. In a mouse model, L. plantarum CCFM639 treatment was found to significantly alleviate oxidative stress in the intestinal tract, regulate the function of the intestinal mucosal immune system, restore the integrity of tight junction proteins and maintain intestinal permeability. These results suggest that in addition to Al sequestration, L. plantarum CCFM639 can also inhibit Al absorption by protecting the intestinal barrier, alleviating Al-induced oxidative stress and inflammatory response. Therefore, L. plantarum CCFM639 has the potential to be a dietary supplement ingredient that provides protection against Al-induced gut injury.

  7. Potential of Lactobacillus plantarum CCFM639 in Protecting against Aluminum Toxicity Mediated by Intestinal Barrier Function and Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Leilei Yu

    2016-12-01

    Full Text Available Aluminum (Al is a ubiquitous metal that can seriously harm the health of animals and humans. In our previous study, we demonstrated that Lactobacillus plantarum CCFM639 can decrease Al burden in the tissues of mice by inhibiting intestinal Al absorption. The main aim of the present research was to investigate whether the protection by the strain is also associated with enhancement of the intestinal barrier, alleviation of oxidative stress and modulation of the inflammatory response. In an in vitro cell model, two protection modes (intervention and therapy were examined and the results indicated that L. plantarum CCFM639 alleviated Al-induced cytotoxicity. In a mouse model, L. plantarum CCFM639 treatment was found to significantly alleviate oxidative stress in the intestinal tract, regulate the function of the intestinal mucosal immune system, restore the integrity of tight junction proteins and maintain intestinal permeability. These results suggest that in addition to Al sequestration, L. plantarum CCFM639 can also inhibit Al absorption by protecting the intestinal barrier, alleviating Al-induced oxidative stress and inflammatory response. Therefore, L. plantarum CCFM639 has the potential to be a dietary supplement ingredient that provides protection against Al-induced gut injury.

  8. Poverty alleviation in Uganda: the case for a viable optimum ...

    African Journals Online (AJOL)

    Poverty alleviation is a long and painstaking process. It involves knowing what poverty is, its causes and means of alleviating it. Poverty is one of the scourges including disease and ignorance a combination of which deprives humanity of the basic needs for living. Among the strategies to alleviate poverty is effective ...

  9. Intestinal dendritic cells in the regulation of mucosal immunity

    DEFF Research Database (Denmark)

    Bekiaris, Vasileios; Persson, Emma K.; Agace, William Winston

    2014-01-01

    The intestine presents a huge surface area to the outside environment, a property that is of critical importance for its key functions in nutrient digestion, absorption, and waste disposal. As such, the intestine is constantly exposed to dietary and microbial-derived foreign antigens, to which im...... of the role these subsets play in the regulation of intestinal immune homeostasis and inflammation will help to define novel strategies for the treatment of intestinal pathologies and contribute to improved rational design of mucosal vaccines....... immune cells within the mucosa must suitably respond to maintain intestinal integrity, while also providing the ability to mount effective immune responses to potential pathogens. Dendritic cells (DCs) are sentinel immune cells that play a central role in the initiation and differentiation of adaptive...... immune responses. In the intestinal mucosa, DCs are located diffusely throughout the intestinal lamina propria, within gut-associated lymphoid tissues, including Peyer's patches and smaller lymphoid aggregates, as well as in intestinal-draining lymph nodes, including mesenteric lymph nodes...

  10. Tumor Necrosis Factor Induces Developmental Stage-Dependent Structural Changes in the Immature Small Intestine

    Directory of Open Access Journals (Sweden)

    Kathryn S. Brown

    2014-01-01

    Full Text Available Background. Premature infants are commonly subject to intestinal inflammation. Since the human small intestine does not reach maturity until term gestation, premature infants have a unique challenge, as either acute or chronic inflammation may alter the normal development of the intestinal tract. Tumor necrosis factor (TNF has been shown to acutely alter goblet cell numbers and villus length in adult mice. In this study we tested the effects of TNF on villus architecture and epithelial cells at different stages of development of the immature small intestine. Methods. To examine the effects of TNF-induced inflammation, we injected acute, brief, or chronic exposures of TNF in neonatal and juvenile mice. Results. TNF induced significant villus blunting through a TNF receptor-1 (TNFR1 mediated mechanism, leading to loss of villus area. This response to TNFR1 signaling was altered during intestinal development, despite constant TNFR1 protein expression. Acute TNF-mediated signaling also significantly decreased Paneth cells. Conclusions. Taken together, the morphologic changes caused by TNF provide insight as to the effects of inflammation on the developing intestinal tract. Additionally, they suggest a mechanism which, coupled with an immature immune system, may help to explain the unique susceptibility of the immature intestine to inflammatory diseases such as NEC.

  11. FLLL32, a curcumin analog, ameliorates intestinal injury in necrotizing enterocolitis.

    Science.gov (United States)

    Eckert, Jeffrey; Scott, Brian; Lawrence, Shelley M; Ihnat, Michael; Chaaban, Hala

    2017-01-01

    Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease that primarily affects premature infants. It is characterized by inflammation and leukocyte infiltration that can progress to intestinal necrosis, perforation, systemic inflammatory response, and death. In this study, we examined the effect of FLLL32, a curcumin analog, on an NEC-like neonatal intestinal injury model. NEC was induced in CD-1 mice pups using the Paneth cell ablation and Klebsiella infection model. Pups were divided into sham, NEC, and NEC + FLLL32 groups. At the end of the experiment, pups were euthanized; whole blood and small intestines were harvested. Intestinal inflammatory cytokine profile, in vivo intestinal permeability using serum fluorescein isothiocyanate-dextran, and histological injury scores were compared between the groups. FLLL32-treated pups had lower intestinal injury, improved intestinal permeability, and lower proinflammatory cytokine profiles compared to those in untreated pups with NEC. These results suggest that FLLL32 plays a protective role in NEC.

  12. Intestinal mast cells in gut inflammation and motility disturbances

    NARCIS (Netherlands)

    de Winter, Benedicte Y.; van den Wijngaard, Rene M.; de Jonge, Wouter J.

    2012-01-01

    Mast cells may be regarded as prototypes of innate immune cells that can be controlled by neuronal mediators. Their activation has been implicated in many types of neuro-inflammatory responses, and related disturbances of gut motility, via direct or indirect mechanisms that involve several

  13. Toxoplasma polymorphic effectors determine macrophage polarization and intestinal inflammation

    NARCIS (Netherlands)

    Jensen, K.D.C.; Wang, Y.; Tait Wonjo, E.D.; Shastri, A.J.; Hu, K.; Cornel, L.; Boedec, E.; Ong, Y.C.; Chien, Y.H.; Hunter, C.A.; Boothroyd, J.C.; Saeij, J.P.J.

    2011-01-01

    European and North American strains of the parasite Toxoplasma gondii belong to three distinct clonal lineages, type I, type II, and type III, which differ in virulence. Understanding the basis of Toxoplasma strain differences and how secreted effectors work to achieve chronic infection is a major

  14. Autophagy and tight junction proteins in the intestine and intestinal diseases

    Directory of Open Access Journals (Sweden)

    Chien-An A. Hu

    2015-09-01

    Full Text Available The intestinal epithelium (IE forms an indispensible barrier and interface between the intestinal interstitium and the luminal environment. The IE regulates water, ion and nutrient transport while providing a barrier against toxins, pathogens (bacteria, fungi and virus and antigens. The apical intercellular tight junctions (TJ are responsible for the paracellular barrier function and regulate trans-epithelial flux of ions and solutes between adjacent cells. Increased intestinal permeability caused by defects in the IE TJ barrier is considered an important pathogenic factor for the development of intestinal inflammation, diarrhea and malnutrition in humans and animals. In fact, defects in the IE TJ barrier allow increased antigenic penetration, resulting in an amplified inflammatory response in inflammatory bowel disease (IBD, necrotizing enterocolitis and ischemia-reperfusion injury. Conversely, the beneficial enhancement of the intestinal TJ barrier has been shown to resolve intestinal inflammation and apoptosis in both animal models of IBD and human IBD. Autophagy (self-eating mechanism is an intracellular lysosome-dependent degradation and recycling pathway essential for cell survival and homeostasis. Dysregulated autophagy has been shown to be directly associated with many pathological processes, including IBD. Importantly, the crosstalk between IE TJ and autophagy has been revealed recently. We showed that autophagy enhanced IE TJ barrier function by increasing transepithelial resistance and reducing the paracellular permeability of small solutes and ions, which is, in part, by targeting claudin-2, a cation-selective, pore-forming, transmembrane TJ protein, for lysosome (autophagy-mediated degradation. Interestingly, previous studies have shown that the inflamed intestinal mucosa in patients with active IBD has increased claudin-2 expression. In addition, inflammatory cytokines (for example, tumor necrosis factor-α, interleukin-6

  15. Intestinal Microbiota and the Innate Immune System - A Crosstalk in Crohn's Disease Pathogenesis.

    Science.gov (United States)

    Haag, Lea-Maxie; Siegmund, Britta

    2015-01-01

    Crohn's disease (CD) is a chronic, relapsing inflammatory disorder that can occur anywhere along the gastrointestinal tract. The precise etiology of CD is still unclear but it is widely accepted that a complex series of interactions between susceptibility genes, the immune system and environmental factors are implicated in the onset and perpetuation of the disease. Increasing evidence from experimental and clinical studies implies the intestinal microbiota in disease pathogenesis, thereby supporting the hypothesis that chronic intestinal inflammation arises from an abnormal immune response against the microorganisms of the intestinal flora in genetically susceptible individuals. Given that CD patients display changes in their gut microbiota composition, collectively termed "dysbiosis," the question raises whether the altered microbiota composition is a cause of disease or rather a consequence of the inflammatory state of the intestinal environment. This review will focus on the crosstalk between the gut microbiota and the innate immune system during intestinal inflammation, thereby unraveling the role of the microbiota in CD pathogenesis.

  16. Intestinal parasites and tuberculosis

    Directory of Open Access Journals (Sweden)

    Anuar Alonso Cedeño-Burbano

    2017-10-01

    Conclusions: The available evidence was insufficient to affirm that intestinal parasites predispose to developing tuberculous. The studies carried out so far have found statistically insignificant results.

  17. Nutritional components regulate the gut immune system and its association with intestinal immune disease development.

    Science.gov (United States)

    Lamichhane, Aayam; Kiyono, Hiroshi; Kunisawa, Jun

    2013-12-01

    The gut is equipped with a unique immune system for maintaining immunological homeostasis, and its functional immune disruption can result in the development of immune diseases such as food allergy and intestinal inflammation. Accumulating evidence has demonstrated that nutritional components play an important role in the regulation of gut immune responses and also in the development of intestinal immune diseases. In this review, we focus on the immunological functions of lipids, vitamins, and nucleotides in the regulation of the intestinal immune system and as potential targets for the control of intestinal immune diseases. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  18. Lamin-B in systemic inflammation, tissue homeostasis, and aging.

    Science.gov (United States)

    Chen, Haiyang; Zheng, Xiaobin; Zheng, Yixian

    2015-01-01

    Gradual loss of tissue function (or homeostasis) is a natural process of aging and is believed to cause many age-associated diseases. In human epidemiology studies, the low-grade and chronic systemic inflammation in elderly has been correlated with the development of aging related pathologies. Although it is suspected that tissue decline is related to systemic inflammation, the cause and consequence of these aging phenomena are poorly understood. By studying the Drosophila fat body and gut, we have uncovered a mechanism by which lamin-B loss in the fat body upon aging induces age-associated systemic inflammation. This chronic inflammation results in the repression of gut local immune response, which in turn leads to the over-proliferation and mis-differentiation of the intestinal stem cells, thereby resulting in gut hyperplasia. Here we discuss the implications and remaining questions in light of our published findings and new observations.

  19. Dietary l-arginine inhibits intestinal Clostridium perfringens colonisation and attenuates intestinal mucosal injury in broiler chickens.

    Science.gov (United States)

    Zhang, Beibei; Lv, Zengpeng; Li, Huixian; Guo, Shuangshuang; Liu, Dan; Guo, Yuming

    2017-09-01

    We investigated the effects of dietary l-arginine level and feeding duration on the intestinal damage of broilers induced by Clostridium perfringens (CP) in vivo, and the antimicrobial effect of its metabolite nitric oxide (NO) in vitro. The in vivo experiment was designed as a factorial arrangement of three dietary treatments×two challenge statuses. Broilers were fed a basal diet (CON) or a high-arginine diet (ARG) containing 1·87 % l-arginine, or CON for the first 8 d and ARG from days 9 to 28 (CON/ARG). Birds were co-infected with or without Eimeria and CP (EM/CP). EM/CP challenge led to intestinal injury, as evidenced by lower plasma d-xylose concentration (Pl-arginine supplementation (Pl-arginine supplementation (Pl-arginine supplementation elevated (Pl-arginine supplementation could inhibit CP overgrowth and alleviate intestinal mucosal injury by modulating innate immune responses, enhancing barrier function and producing NO.

  20. Hypoxia and Mucosal Inflammation

    Science.gov (United States)

    Colgan, Sean P.; Campbell, Eric L.; Kominsky, Douglas J.

    2016-01-01

    Sites of inflammation are defined by significant changes in metabolic activity. Recent studies have suggested that O2 metabolism and hypoxia play a prominent role in inflammation so-called “inflammatory hypoxia,” which results from a combination of recruited inflammatory cells (e.g., neutrophils and monocytes), the local proliferation of multiple cell types, and the activation of multiple O2-consuming enzymes during inflammation. These shifts in energy supply and demand result in localized regions of hypoxia and have revealed the important function off the transcription factor HIF (hypoxia-inducible factor) in the regulation of key target genes that promote inflammatory resolution. Analysis of these pathways has provided multiple opportunities for understanding basic mechanisms of inflammation and has defined new targets for intervention. Here, we review recent work addressing tissue hypoxia and metabolic control of inflammation and immunity. PMID:27193451

  1. Endocannabinoids alleviate proinflammatory conditions by modulating innate immune response in muller glia during inflammation.

    Science.gov (United States)

    Krishnan, Gopinath; Chatterjee, Nivedita

    2012-11-01

    Muller cells play a prominent role in inflammatory conditions of the retina. They are part of the retinal innate immune response. The endocannabinoid system functions as an immune modulator in both the peripheral immune system as well as the central nervous system. We hypothesized that the neuroprotective ability of exogenous endocannabinoids in the retina is partially mediated through Muller glia. This study reports that exposure to endocannabinoids in activated but not resting primary human Muller glia inhibit production of several proinflammatory cytokines, while elevating anti-inflammatory mediators. Cytokine generation in activated Muller glia is regulated by endocannabinoids through the mitogen-activated protein kinase (MAPK) family at multiple signaling stages. Anandamide (AEA) acts to control MAPK phosphorylation through MKP-1. Both AEA and 2-arachidonoylglycerol (2-AG) inhibit the transcription factor NF-κB and increases the regulatory protein, IL1-R-associated kinase 1-binding protein 1. Endocannabinoids also increase expression of Tristetraprolin in activated Muller cells, which is implicated in affecting AU-rich proinflammatory cytokine mRNA. We demonstrate that exogenous application of AEA and 2-AG aid in retinal cell survival under inflammatory conditions by creating an anti-inflammatory milieu. Endocannabinoids or synthetic cannabinoid therapy may therefore orchestrate a molecular switch to bias the innate immune system suchthat the balance of pro- and anti-inflammatory cytokine generation creates a prosurvival milieu. Copyright © 2012 Wiley Periodicals, Inc.

  2. Ethnic and paleolithic diet: Where do they stand in inflammation alleviation? A discussion

    Directory of Open Access Journals (Sweden)

    Seema Patel

    2017-12-01

    To quell the morbidities and mortalities associated with the metabolic syndromes, nonpharmacologic approaches are preferred. Dietary interventions are critical in this regard. Among the array of dietary patterns, paleo diet has garnered much attention in the last decade. This diet rich in phytochemicals and unsaturated fatty acids is deemed wholesome for the body. Several studies have proven this claim, yet their nutritional adequacy for all age groups is contentious. The popularity of ethnic foods is rising; but their nutrition and safety position can vary. Although some of them are close to paleo food, some are unhealthy. This review explores the mechanism by which paleo diet restores homeostasis of the body and how its inherent nutritional deficiency can be amended with conventional diet, by the formulation of personalized diet. This compilation is expected to be insightful for dietary optimization.

  3. The essential oil from the twigs of Cinnamomum cassia Presl alleviates pain and inflammation in mice.

    Science.gov (United States)

    Sun, Lan; Zong, Shao-Bo; Li, Jia-Chun; Lv, Yao-Zhong; Liu, Li-Na; Wang, Zheng-Zhong; Zhou, Jun; Cao, Liang; Kou, Jun-Ping; Xiao, Wei

    2016-12-24

    Cinnamomum cassia Presl (Lauraceae) can be found southern China and its bark is commonly used for centuries as ingredient in food and cosmetic industry. The twigs of Cinnamomum cassia Presl is popularly used in China to treat inflammatory processes, pain, menstrual disorders, hypertension, fever etc. The aim of this study is to evaluate the antinociceptive and anti-inflammatory properties of the essential oil (EO) from the twigs of Cinnamomum cassia Presl. The chemical characterization of the EO was performed by gas chromatography coupled with mass spectrometry (GC-MS). The EO doses of 15, 30, and 60mg/kg were employed in the biological assays. The antinociceptive effects of the EO were evaluated using the models of acetic acid-induced writhing, oxytocin-induced writhing, and formalin and complete Freund's adjuvant (CFA) -induced overt pain tests. we also investigated the effect of the EO in pain intensity to a mechanical stimulus (mechanical hyperalgesia) after carrageenan by using an electronic version of von Frey filaments. Evaluation of anti-inflammatory activity was based on paw edema induced by carrageenan (300µg/25µL/paw) in mice. The levels of cytokines, NO, and PGE2 in paw skin tissue were determined according to instructions. COX-2 and iNOS proteins in paw skin tissue were assessed by Western Blot. The EO (15, 30, and 60mg/kg) reduced the number of abdominal writhings induced by acetic acid with inhibition of 38.0%, 55.4% and 58.7%, respectively. The EO (15, 30, and 60mg/kg) also reduced the number of abdominal writhings induced by oxytocin with inhibition of 27.3%, 51.7% and 69.0%, respectively. The EO significant inhibited the inflammatory (second phase: 10-30min) phase of the formalin-induced paw flinching and licking at the doses of 15, 30, and 60mg/kg. The EO at the tested doses of 15, 30, and 60mg/kg showed inhibited CFA-induced paw flinching and licking. The EO (15, 30, and 60mg/kg) also inhibited carrageenan-induced mechanical hyperalgesia and paw edema. It also decreased the levels of cytokines (TNF-α, and IL-1β), NO, and PGE2 in carrageenan-induced mice paw skin tissue. Moreover, Western blot analysis showed that COX-2 and iNOS expressions in paw skin tissue of mice were significantly reduced. These results demonstrate that the antinociceptive and anti-inflammatory properties of the EO from the twigs of Cinnamomum cassia Presl, corroborating its use in folk medicine. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. HemoHIM, a herbal preparation, alleviates airway inflammation caused by cigarette smoke and lipopolysaccharide

    OpenAIRE

    Shin, Na-Rae; Kim, Sung-Ho; Ko, Je-Won; Park, Sung-Hyeuk; Lee, In-Chul; Ryu, Jung-Min; Kim, Jong-Choon; Shin, In-Sik

    2017-01-01

    HemoHIM, herbal preparation has designed for immune system recovery. We investigated the anti-inflammatory effect of HemoHIM on cigarette smoke (CS) and lipopolysaccharide (LPS) induced chronic obstructive pulmonary disease (COPD) mouse model. To induce COPD, C57BL/6 mice were exposed to CS for 1 h per day (eight cigarettes per day) for 4 weeks and intranasally received LPS on day 26. HemoHIM was administrated to mice at a dose of 50 or 100 mg/kg 1h before CS exposure. HemoHIM reduced the inf...

  5. adhesive intestinal obstruction

    African Journals Online (AJOL)

    2006-06-01

    Jun 1, 2006 ... ABSTRACT. Background: Adhesions after abdominal and pelvic surgery are a major cause of intestinal obstruction in the western world and the pathology is steadily gaining prominence in our practice. Objective: To determine the magnitude of adhesive intestinal obstruction; to determine the types.

  6. Alleviating soil acidity through plant organic compounds

    Directory of Open Access Journals (Sweden)

    Meda Anderson R.

    2001-01-01

    Full Text Available A laboratory experiment was conducted to evaluate the effects of water soluble plant extracts on soil acidity. The plant materials were: black oat, oil seed radish, white and blue lupin, gray and dwarf mucuna, Crotalaria spectabilis and C. breviflora, millet, pigeon pea, star grass, mato grosso grass, coffee leaves, sugar cane leaves, rice straw, and wheat straw. Plant extracts were added on soil surface in a PVC soil column at a rate of 1.0 ml min-1. Both soil and drainage water were analyzed for pH, Ca, Al, and K. Plant extracts applied on the soil surface increased soil pH, exchangeable Ca ex and Kex and decreased Al ex. Oil seed radish, black oat, and blue lupin were the best and millet the worst materials to alleviate soil acidity. Oil seed radish markedly increased Al in the drainage water. Chemical changes were associated with the concentrations of basic cations in the plant extract: the higher the concentration the greater the effects in alleviating soil acidity.

  7. Neural predictive control for active buffet alleviation

    Science.gov (United States)

    Pado, Lawrence E.; Lichtenwalner, Peter F.; Liguore, Salvatore L.; Drouin, Donald

    1998-06-01

    The adaptive neural control of aeroelastic response (ANCAR) and the affordable loads and dynamics independent research and development (IRAD) programs at the Boeing Company jointly examined using neural network based active control technology for alleviating undesirable vibration and aeroelastic response in a scale model aircraft vertical tail. The potential benefits of adaptive control includes reducing aeroelastic response associated with buffet and atmospheric turbulence, increasing flutter margins, and reducing response associated with nonlinear phenomenon like limit cycle oscillations. By reducing vibration levels and thus loads, aircraft structures can have lower acquisition cost, reduced maintenance, and extended lifetimes. Wind tunnel tests were undertaken on a rigid 15% scale aircraft in Boeing's mini-speed wind tunnel, which is used for testing at very low air speeds up to 80 mph. The model included a dynamically scaled flexible fail consisting of an aluminum spar with balsa wood cross sections with a hydraulically powered rudder. Neural predictive control was used to actuate the vertical tail rudder in response to strain gauge feedback to alleviate buffeting effects. First mode RMS strain reduction of 50% was achieved. The neural predictive control system was developed and implemented by the Boeing Company to provide an intelligent, adaptive control architecture for smart structures applications with automated synthesis, self-optimization, real-time adaptation, nonlinear control, and fault tolerance capabilities. It is designed to solve complex control problems though a process of automated synthesis, eliminating costly control design and surpassing it in many instances by accounting for real world non-linearities.

  8. Effect of ecoimmunonutrition supports on maintenance of integrity of intestinal mucosal barrier in severe acute pancreatitis in dogs.

    Science.gov (United States)

    Xu, Gui-fang; Lu, Zheng; Gao, Jun; Li, Zhao-shen; Gong, Yan-fang

    2006-04-20

    One of the major causes of death in severe acute pancreatitis (SAP) is severe infection owing to bacterial translocation. Some clinical studies suggested that ecoimmunonutrition (EIN) as a new strategy had better treatment effect on SAP patients. But the experiment studies on the precise mechanism of the effect of EIN were less reported. In this study, we mainly investigated the effects of EIN on bacterial translocation in SAP model of dogs. SAP was induced by retrograde infusion of 5% sodium taurocholate into the pancreatic duct in healthy hybrid dogs. The SAP dogs were supported with either parenteral nutrition (PN) or elemental enteral nutrition (EEN) or EIN. The levels of serum amylase, serum aminotransferase and plasma endotoxin were detected before and after pancreatitis induction. On the 7th day after nutrition supports, peritoneal fluid, mesenteric lymph nodes (MLN), liver, and pancreas were collected for bacterial culture with standard techniques to observe the incidence of bacterial translocation. Pathology changes of pancreas were analyzed by histopathologic grading and scoring of the severity of pancreas, and the degree of intestinal mucosal damage was assessed by measuring mucosal thickness, villus height, and crypt depth of ileum. Compared with PN and EEN, EIN significantly decreased the levels of serum amylase, serum aminotransferase, plasma endotoxin, and the incidence of bacterial translocation. Furthermore, compared with the others, the histology scores of inflammation in pancreas and the ileum injury (ileum mocosa thickness, villus height, and crypt depth) were significantly alleviated by EIN (P dogs. Early EIN was safe and more effective treatment for SAP dogs.

  9. Tumor necrosis factor receptor 1-dependent depletion of mucus in immature small intestine: a potential role in neonatal necrotizing enterocolitis

    OpenAIRE

    McElroy, Steven J.; Prince, Lawrence S.; Weitkamp, Jörn-Hendrik; Reese, Jeff; Slaughter, James C.; Polk, D. Brent

    2011-01-01

    Necrotizing enterocolitis (NEC) is a leading cause of morbidity and mortality in premature infants. NEC is believed to occur when intestinal bacteria invade the intestinal epithelial layer, causing subsequent inflammation and tissue necrosis. Mucins are produced and secreted by epithelial goblet cells as a key component of the innate immune system and barrier function of the intestinal tract that help protect against bacterial invasion. To better understand the role of mucins in NEC, we quant...

  10. Immunopathophysiology of inflammatory bowel disease: how genetics link barrier dysfunction and innate immunity to inflammation.

    Science.gov (United States)

    Mehta, Minesh; Ahmed, Shifat; Dryden, Gerald

    2017-08-01

    Inflammatory bowel diseases (IBD) comprise a distinct set of clinical symptoms resulting from chronic or relapsing immune activation and corresponding inflammation within the gastrointestinal (GI) tract. Diverse genetic mutations, encoding important aspects of innate immunity and mucosal homeostasis, combine with environmental triggers to create inappropriate, sustained inflammatory responses. Recently, significant advances have been made in understanding the interplay of the intestinal epithelium, mucosal immune system, and commensal bacteria as a foundation of the pathogenesis of inflammatory bowel disease. Complex interactions between specialized intestinal epithelial cells and mucosal immune cells determine different outcomes based on the environmental input: the development of tolerance in the presence of commensal bacterial or the promotion of inflammation upon recognition of pathogenic organisms. This article reviews key genetic abnormalities involved in inflammatory and homeostatic pathways that enhance susceptibility to immune dysregulation and combine with environmental triggers to trigger the development of chronic intestinal inflammation and IBD.

  11. Pancreatic Digestive Enzyme Blockade in the Intestine Increases Survival After Experimental Shock

    Science.gov (United States)

    DeLano, Frank A.; Hoyt, David B.; Schmid-Schönbein, Geert W.

    2015-01-01

    Shock, sepsis, and multiorgan failure are associated with inflammation, morbidity, and high mortality. The underlying pathophysiological mechanism is unknown, but evidence suggests that pancreatic enzymes in the intestinal lumen autodigest the intestine and generate systemic inflammation. Blocking these enzymes in the intestine reduces inflammation and multiorgan dysfunction. We investigated whether enzymatic blockade also reduces mortality after shock. Three rat shock models were used here: hemorrhagic shock, peritonitis shock induced by placement of cecal material into the peritoneum, and endotoxin shock. One hour after initiation of hemorrhagic, peritonitis, or endotoxin shock, animals were administered one of three different pancreatic enzyme inhibitors—6-amidino-2-naphtyl p-guanidinobenzoate di-methanesulfate, tranexamic acid, or aprotinin—into the lumen of the small intestine. In all forms of shock, blockade of digestive proteases with protease inhibitor attenuated entry of digestive enzymes into the wall of the intestine and subsequent autodigestion and morphological damage to the intestine, lung, and heart. Animals treated with protease inhibitors also survived in larger numbers than untreated controls over a period of 12 weeks. Surviving animals recovered completely and returned to normal weight within 14 days after shock. The results suggest that the active and concentrated digestive enzymes in the lumen of the intestine play a central role in shock and multi-organ failure, which can be treated with protease inhibitors that are currently available for use in the clinic. PMID:23345609

  12. Fundamentals of inflammation

    National Research Council Canada - National Science Library

    Serhan, Charles N; Ward, Peter A; Gilroy, Derek W

    2010-01-01

    .... Uncontrolled inflammation has emerged as a pathophysiologic basis for many widely occurring diseases in the general population that were not initially known to be linked to the inflammatory response...

  13. Alleviate Cellular Congestion Through Opportunistic Trough Filling

    Directory of Open Access Journals (Sweden)

    Yichuan Wang

    2014-04-01

    Full Text Available The demand for cellular data service has been skyrocketing since the debut of data-intensive smart phones and touchpads. However, not all data are created equal. Many popular applications on mobile devices, such as email synchronization and social network updates, are delay tolerant. In addition, cellular load varies significantly in both large and small time scales. To alleviate network congestion and improve network performance, we present a set of opportunistic trough filling schemes that leverage the time-variation of network congestion and delay-tolerance of certain traffic in this paper. We consider average delay, deadline, and clearance time as the performance metrics. Simulation results show promising performance improvement over the standard schemes. The work shed lights on addressing the pressing issue of cellular overload.

  14. Rainwater harvesting for drought disaster alleviation

    International Nuclear Information System (INIS)

    Widodo, B.; Prinzand, D.; Malik, A.H.

    2005-01-01

    Too little water and too much water can be as devastating as well. Drought usually does not show up instantly like flood, but it creeps slowly. Drought that is less popular than flood has impact more serious than flood. It is difficult to be identified when it comes and when it goes away. However, it is suddenly understood when water becomes scare, or no more water is available in wells, rivers and reservoirs. Managing flood and drought has to be at an integrated basis. Rainwater harvesting (RWH) combined with water conservation methods can be developed to alleviate drought disaster as well as flood disaster in the same time. RWH and water conservation must be an integral part of integrated water resources management. Preventing drought could be automatically reducing the extent of flood that means preventing people and the environment from the disasters. (author)

  15. Debug your bugs-how NLRs shape intestinal host-microbe interactions

    Directory of Open Access Journals (Sweden)

    Philip eRosenstiel

    2013-12-01

    Full Text Available The host’s ability to discriminate friend and foe and to establish a precise homeostasis with its associated microbiota is crucial for its survival and fitness. Among the mediators of intestinal host-microbe interactions, NOD-like receptor (NLR proteins take center stage. They are present in the epithelial lining and innate immune cells that constantly monitor microbial activities at the intestinal barrier. Dysfunctional NLRs predispose to intestinal inflammation as well as sensitization to extra-intestinal immune-mediated diseases and are linked to the alteration of microbial communities. Here, we review advances in our understanding of their reciprocal relationship in the regulation of intestinal homeostasis and implications for intestinal health.

  16. Intestinal solute carriers

    DEFF Research Database (Denmark)

    Steffansen, Bente; Nielsen, Carsten Uhd; Brodin, Birger

    2004-01-01

    A large amount of absorptive intestinal membrane transporters play an important part in absorption and distribution of several nutrients, drugs and prodrugs. The present paper gives a general overview on intestinal solute carriers as well as on trends and strategies for targeting drugs and...... membrane transporters in the small intestine in order to increase oral bioavailabilities of drug or prodrug, the major influence on in vivo pharmacokinetics is suggested to be dose-dependent increase in bioavailability as well as prolonged blood circulation due to large capacity facilitated absorption...

  17. Intestinal solute carriers

    DEFF Research Database (Denmark)

    Steffansen, Bente; Nielsen, Carsten Uhd; Brodin, Birger

    2004-01-01

    membrane transporters in the small intestine in order to increase oral bioavailabilities of drug or prodrug, the major influence on in vivo pharmacokinetics is suggested to be dose-dependent increase in bioavailability as well as prolonged blood circulation due to large capacity facilitated absorption......A large amount of absorptive intestinal membrane transporters play an important part in absorption and distribution of several nutrients, drugs and prodrugs. The present paper gives a general overview on intestinal solute carriers as well as on trends and strategies for targeting drugs and...

  18. Factors Influencing the Gut Microbiota, Inflammation, and Type 2 Diabetes.

    Science.gov (United States)

    Wen, Li; Duffy, Andrew

    2017-07-01

    The gut microbiota is a complex community of bacteria residing in the intestine. Animal models have demonstrated that several factors contribute to and can significantly alter the composition of the gut microbiota, including genetics; the mode of delivery at birth; the method of infant feeding; the use of medications, especially antibiotics; and the diet. There may exist a gut microbiota signature that promotes intestinal inflammation and subsequent systemic low-grade inflammation, which in turn promotes the development of type 2 diabetes. There are preliminary studies that suggest that the consumption of probiotic bacteria such as those found in yogurt and other fermented milk products can beneficially alter the composition of the gut microbiome, which in turn changes the host metabolism. Obesity, insulin resistance, fatty liver disease, and low-grade peripheral inflammation are more prevalent in patients with low α diversity in the gut microbiome than they are in patients with high α diversity. Fermented milk products, such as yogurt, deliver a large number of lactic acid bacteria to the gastrointestinal tract. They may modify the intestinal environment, including inhibiting lipopolysaccharide production and increasing the tight junctions of gut epithelia cells. © 2017 American Society for Nutrition.

  19. Wine consumption and intestinal redox homeostasis

    Science.gov (United States)

    Biasi, Fiorella; Deiana, Monica; Guina, Tina; Gamba, Paola; Leonarduzzi, Gabriella; Poli, Giuseppe

    2014-01-01

    Regular consumption of moderate doses of wine is an integral part of the Mediterranean diet, which has long been considered to provide remarkable health benefits. Wine׳s beneficial effect has been attributed principally to its non-alcoholic portion, which has antioxidant properties, and contains a wide variety of phenolics, generally called polyphenols. Wine phenolics may prevent or delay the progression of intestinal diseases characterized by oxidative stress and inflammation, especially because they reach higher concentrations in the gut than in other tissues. They act as both free radical scavengers and modulators of specific inflammation-related genes involved in cellular redox signaling. In addition, the importance of wine polyphenols has recently been stressed for their ability to act as prebiotics and antimicrobial agents. Wine components have been proposed as an alternative natural approach to prevent or treat inflammatory bowel diseases. The difficulty remains to distinguish whether these positive properties are due only to polyphenols in wine or also to the alcohol intake, since many studies have reported ethanol to possess various beneficial effects. Our knowledge of the use of wine components in managing human intestinal inflammatory diseases is still quite limited, and further clinical studies may afford more solid evidence of their beneficial effects. PMID:25009781

  20. Prophylactic Ozone Administration Reduces Intestinal Mucosa Injury Induced by Intestinal Ischemia-Reperfusion in the Rat

    Directory of Open Access Journals (Sweden)

    Ozkan Onal

    2015-01-01

    prevented intestine from ischemia reperfusion injury. It is thought that the therapeutic effect of ozone is associated with increase in antioxidant enzymes and protection of cells from oxidation and inflammation.

  1. Lactococcus lactis expressing food-grade β-galactosidase alleviates lactose intolerance symptoms in post-weaning Balb/c mice.

    Science.gov (United States)

    Li, Jingjie; Zhang, Wen; Wang, Chuan; Yu, Qian; Dai, Ruirui; Pei, Xiaofang

    2012-12-01

    The endogenous β-galactosidase expressed in intestinal microbes is demonstrated to help humans in lactose usage, and treatment associated with the promotion of beneficial microorganism in the gut is correlated with lactose tolerance. From this point, a kind of recombinant live β-galactosidase delivery system using food-grade protein expression techniques and selected probiotics as vehicle was promoted by us for the purpose of application in lactose intolerance subjects. Previously, a recombinant Lactococcus lactis MG1363 strain expressing food-grade β-galactosidase, the L. lactis MG1363/FGZW, was successfully constructed and evaluated in vitro. This study was conducted to in vivo evaluate its efficacy on alleviating lactose intolerance symptoms in post-weaning Balb/c mice, which were orally administered with 1 × 10⁶ CFU or 1 × 10⁸ CFU of L. lactis MG1363/FGZW daily for 4 weeks before lactose challenge. In comparison with naïve mice, the mice administered with L. lactis MG1363/FGZW showed significant alleviation of diarrhea symptoms in less total feces weight within 6 h post-challenge and suppressed intestinal motility after lactose challenge, although there was no significant increase of β-galactosidase activity in small intestine. The alleviation also correlated with higher species abundance, more Bifidobacterium colonization, and stronger colonization resistance in mice intestinal microflora. Therefore, this recombinant L. lactis strain effectively alleviated diarrhea symptom induced by lactose uptake in lactose intolerance model mice with the probable mechanism of promotion of lactic acid bacteria to differentiate and predominantly colonize in gut microbial community, thus making it a promising probiotic for lactose intolerance subjects.

  2. The enteric nervous system promotes intestinal health by constraining microbiota composition.

    Directory of Open Access Journals (Sweden)

    Annah S Rolig

    2017-02-01

    Full Text Available Sustaining a balanced intestinal microbial community is critical for maintaining intestinal health and preventing chronic inflammation. The gut is a highly dynamic environment, subject to periodic waves of peristaltic activity. We hypothesized that this dynamic environment is a prerequisite for a balanced microbial community and that the enteric nervous system (ENS, a chief regulator of physiological processes within the gut, profoundly influences gut microbiota composition. We found that zebrafish lacking an ENS due to a mutation in the Hirschsprung disease gene, sox10, develop microbiota-dependent inflammation that is transmissible between hosts. Profiling microbial communities across a spectrum of inflammatory phenotypes revealed that increased levels of inflammation were linked to an overabundance of pro-inflammatory bacterial lineages and a lack of anti-inflammatory bacterial lineages. Moreover, either administering a representative anti-inflammatory strain or restoring ENS function corrected the pathology. Thus, we demonstrate that the ENS modulates gut microbiota community membership to maintain intestinal health.

  3. The enteric nervous system promotes intestinal health by constraining microbiota composition

    Science.gov (United States)

    Mittge, Erika K.; Ganz, Julia; Troll, Josh V.; Melancon, Ellie; Wiles, Travis J.; Alligood, Kristin; Stephens, W. Zac; Eisen, Judith S.; Guillemin, Karen

    2017-01-01

    Sustaining a balanced intestinal microbial community is critical for maintaining intestinal health and preventing chronic inflammation. The gut is a highly dynamic environment, subject to periodic waves of peristaltic activity. We hypothesized that this dynamic environment is a prerequisite for a balanced microbial community and that the enteric nervous system (ENS), a chief regulator of physiological processes within the gut, profoundly influences gut microbiota composition. We found that zebrafish lacking an ENS due to a mutation in the Hirschsprung disease gene, sox10, develop microbiota-dependent inflammation that is transmissible between hosts. Profiling microbial communities across a spectrum of inflammatory phenotypes revealed that increased levels of inflammation were linked to an overabundance of pro-inflammatory bacterial lineages and a lack of anti-inflammatory bacterial lineages. Moreover, either administering a representative anti-inflammatory strain or restoring ENS function corrected the pathology. Thus, we demonstrate that the ENS modulates gut microbiota community membership to maintain intestinal health. PMID:28207737

  4. FLLL32, a curcumin analog, ameliorates intestinal injury in necrotizing enterocolitis

    Directory of Open Access Journals (Sweden)

    Eckert J

    2017-06-01

    Full Text Available Jeffrey Eckert,1 Brian Scott,1,2 Shelley M Lawrence,3 Michael Ihnat,4 Hala Chaaban1 1Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 2Department of Pediatrics, University of Texas Health Science Center at San Antonio, San Antonio, TX, 3Department of Pediatrics, University of California San Diego, San Diego, CA, 4Department of Pharmaceutical Sciences, University of Oklahoma, College of Pharmacy, Oklahoma City, OK, USA Background: Necrotizing enterocolitis (NEC is a devastating gastrointestinal disease that primarily affects premature infants. It is characterized by inflammation and leukocyte infiltration that can progress to intestinal necrosis, perforation, systemic inflammatory response, and death. In this study, we examined the effect of FLLL32, a curcumin analog, on an NEC-like neonatal intestinal injury model. Methods: NEC was induced in CD-1 mice pups using the Paneth cell ablation and Klebsiella infection model. Pups were divided into sham, NEC, and NEC + FLLL32 groups. At the end of the experiment, pups were euthanized; whole blood and small intestines were harvested. Intestinal inflammatory cytokine profile, in vivo intestinal permeability using serum fluorescein isothiocyanate-dextran, and histological injury scores were compared between the groups. Results and conclusion: FLLL32-treated pups had lower intestinal injury, improved intestinal permeability, and lower proinflammatory cytokine profiles compared to those in untreated pups with NEC. These results suggest that FLLL32 plays a protective role in NEC. Keywords: necrotizing enterocolitis, neonatal intestinal inflammation, curcumin, FLLL32, STAT3 inhibitors

  5. Impact of government poverty alleviation programmes on the socio ...

    African Journals Online (AJOL)

    Despite these programmes, poverty still exists among Nigerians especially the youth. This study therefore examines the impact of government poverty alleviation programmes on the youth. The population of the study comprised of all youths who have benefited from government poverty alleviation programmes. The Random ...

  6. An Appraisal of Poverty Alleviation Programmes in Nigeria | Forae ...

    African Journals Online (AJOL)

    An Appraisal of Poverty Alleviation Programmes in Nigeria. OF Forae, AO Benedict. Abstract. The paper analyses Nigerias past poverty alleviation measures as well as assessing the reasons for their inability to achieve set goals and targets. It is also aimed at formulating a framework for building and implementing future ...

  7. Where Does Inflammation Fit?

    Science.gov (United States)

    Biasucci, Luigi M; La Rosa, Giulio; Pedicino, Daniela; D'Aiello, Alessia; Galli, Mattia; Liuzzo, Giovanna

    2017-09-01

    This review focuses on the complex relationship between inflammation and the onset of acute coronary syndrome and heart failure. In the last few years, two important lines of research brought new and essential information to light in the pathogenesis of acute coronary syndrome: a) the understanding of the immune mediate mechanisms of inflammation in Ischemic Heart Disease (IHD) and b) evidence that the inflammatory mechanisms associated with atherosclerosis and its complications can be modulated by anti-inflammatory molecules. A large amount of data also suggests that inflammation is a major component in the development and exacerbation of heart failure (HF), in a symbiotic relationship. In particular, recent evidence underlies peculiar aspects of the phenomenon: oxidative stress and autophagy; DAMPS and TLR-4 signaling activation; different macrophages lineage and the contribution of NLRP-3 inflammasome; adaptive immune system. A possible explanation that could unify the pathogenic mechanism of these different conditions is the rising evidence that increased bowel permeability may allow translation of gut microbioma product into the circulation. These findings clearly establish the role of inflammation as the great trigger for two of the major cardiovascular causes of death and morbidity. Further studies are needed, to better clarify the issue and to define more targeted approaches to reduce pathological inflammation while preserving the physiological one.

  8. TRPA1 mediates mechanical sensitization in nociceptors during inflammation.

    Directory of Open Access Journals (Sweden)

    Richard C Lennertz

    Full Text Available Inflammation is a part of the body's natural response to tissue injury which initiates the healing process. Unfortunately, inflammation is frequently painful and leads to hypersensitivity to mechanical stimuli, which is difficult to treat clinically. While it is well established that altered sensory processing in the spinal cord contributes to mechanical hypersensitivity (central sensitization, it is still debated whether primary afferent neurons become sensitized to mechanical stimuli after tissue inflammation. We induced inflammation in C57BL/6 mice via intraplantar injection of Complete Freund's Adjuvant. Cutaneous C fibers exhibited increased action potential firing to suprathreshold mechanical stimuli. We found that abnormal responses to intense mechanical stimuli were completely suppressed by acute incubation of the receptive terminals with the TRPA1 inhibitor, HC-030031. Further, elevated responses were predominantly exhibited by a specific subgroup of C fibers, which we determined to be C-Mechano Cold sensitive fibers. Thus, in the presence of HC-030031, C fiber mechanical responses in inflamed mice were not different than responses in saline-injected controls. We also demonstrate that injection of the HC-030031 compound into the hind paw of inflamed mice alleviates behavioral mechanical hyperalgesia without affecting heat hyperalgesia. Further, we pharmacologically anesthetized the TRPA1-expressing fibers in vivo by co-injecting the membrane-impermeable sodium channel inhibitor QX-314 and the TRPA1 agonist cinnamaldehyde into the hind paw. This approach also alleviated behavioral mechanical hyperalgesia in inflamed mice but left heat hypersensitivity intact. Our findings indicate that C-Mechano Cold sensitive fibers exhibit enhanced firing to suprathreshold mechanical stimuli in a TRPA1-dependent manner during inflammation, and that input from these fibers drives mechanical hyperalgesia in inflamed mice.

  9. Intestinal microbiota in pathophysiology and management of irritable bowel syndrome.

    Science.gov (United States)

    Lee, Kang Nyeong; Lee, Oh Young

    2014-07-21

    Irritable bowel syndrome (IBS) is a functional bowel disorder without any structural or metabolic abnormalities that sufficiently explain the symptoms, which include abdominal pain and discomfort, and bowel habit changes such as diarrhea and constipation. Its pathogenesis is multifactorial: visceral hypersensitivity, dysmotility, psychosocial factors, genetic or environmental factors, dysregulation of the brain-gut axis, and altered intestinal microbiota have all been proposed as possible causes. The human intestinal microbiota are composed of more than 1000 different bacterial species and 10(14) cells, and are essential for the development, function, and homeostasis of the intestine, and for individual health. The putative mechanisms that explain the role of microbiota in the development of IBS include altered composition or metabolic activity of the microbiota, mucosal immune activation and inflammation, increased intestinal permeability and impaired mucosal barrier function, sensory-motor disturbances provoked by the microbiota, and a disturbed gut-microbiota-brain axis. Therefore, modulation of the intestinal microbiota through dietary changes, and use of antibiotics, probiotics, and anti-inflammatory agents has been suggested as strategies for managing IBS symptoms. This review summarizes and discusses the accumulating evidence that intestinal microbiota play a role in the pathophysiology and management of IBS.

  10. The symbiotic bacterial surface factor polysaccharide A on Bacteroides fragilis inhibits IL-1β-induced inflammation in human fetal enterocytes via toll receptors 2 and 4.

    Directory of Open Access Journals (Sweden)

    Fei Jiang

    Full Text Available Colonizing bacteria interacting with the immature, unlike the mature, human intestine favors inflammation over immune homeostasis. As a result, ten percent of premature infants under 1500 grams weight develop an inflammatory necrosis of the intestine after birth, e.g., necrotizing enterocolitis (NEC. NEC is a major health problem in this population causing extensive morbidity and mortality and an enormous expenditure of health care dollars. NEC can be prevented by giving preterm infants their mother's expressed breast milk or ingesting selective probiotic organisms. Vaginally delivered, breast fed newborns develop health promoting bacteria ("pioneer" bacteria which preferentially stimulate intestinal host defense and anti-inflammation. One such "pioneer" organism is Bacteroides fragilis with a polysaccharide (PSA on its capsule. B. fragilis has been shown developmentally in intestinal lymphocytes and dendritic cells to produce a balanced T-helper cell (TH1/TH2 response and to reduce intestinal inflammation by activity through the TLR2 receptor stimulating IL-10 which inhibits IL-17 causing inflammation. No studies have been done on the role of B. fragilis PSA on fetal enterocytes and its increased inflammation. Accordingly, using human and mouse fetal intestinal models, we have shown that B. fragilis with PSA and PSA alone inhibits IL-1β-induced IL-8 inflammation in fetal and NEC intestine. We have also begun to define the mechanism for this unique inflammation noted in fetal intestine. We have shown that B. fragilis PSA anti-inflammation requires both the TLR2 and TLR4 receptor and is in part mediated by the AP1 transcription factor (TLR2 which is developmentally regulated. These observations may help to devise future preventative treatments of premature infants against NEC.

  11. An Online Alternative to Alleviate Communication Apprehension

    Directory of Open Access Journals (Sweden)

    Seyit Ahmet Çapan

    2013-05-01

    Full Text Available Anxiety is an affective factor commonly associated with one’s overall performance in a foreign language. As a component of foreign language anxiety, communication apprehension specifically correlates with successful oral production. A plethora of research (Bailey, Onwuegbuzie & Daley, 2003; Foss & Reitzel, 1988 has indicated that high levels of communication apprehension negatively affects one’s L2 communication abilities. Thus, this study intends to remedy negative effects of communication apprehension on EFL learners by virtual meetings held through computer-mediated communication. The participants (N: 18 in this study were selected through purposive sampling. The study employed both quantitative and qualitative techniques. To analyze the data collected, a non-parametric test, Wilcoxon Signed Rank Test, was utilized. The results indicated that computer-mediated communication via voice over IP tools made a significant contribution to alleviate communication apprehension levels in the participants with varying degrees of apprehension levels. The study yielded the most drastic reduction in the high apprehension group, since the participants in this group made a significant progress and ended up with moderate levels of communication apprehension. Also, the participants’ self-reports revealed that computer-mediated communication yielded remarkably positive changes in their attitudes towards communicating in the target language. Moreover, the study revealed that computer-mediated communication helped to increase their intercultural awareness. Finally, participants provided a bunch of practical suggestions as possible solutions for reducing communication apprehension.

  12. Alleviating energy poverty for the world's poor

    International Nuclear Information System (INIS)

    Sagar, Ambuj D.

    2005-01-01

    Improving energy services for poor households in developing countries remains one of the most pressing challenges facing the development community. The dependence of these households on traditional forms of energy leads to significant health impacts as well as other major disbenefits, yet there has been little progress in meeting this challenge. This viewpoint argues for an 'energy-poverty alleviation' fund to help provide modern energy services to these households. It also proposes an approach through which to create such a fund, namely by introducing an incremental levy on petroleum. Notably, this scheme does not need a global agreement since a levy could be introduced by major oil-exporting countries. The implementation of this mechanism would result in a climate-friendly outcome (even before taking into account the elimination of products of incomplete combustion resulting from the traditional household use of biomass-based fuels) while providing immense socio-economic benefits to the world's poor. Such an approach would allow significant progress on the sustainable development front while reducing global greenhouse gas emissions, and therefore is very much consistent with the United Nations Framework Convention on Climate Change

  13. [Nanometer silver dressing alleviates pain after circumcision].

    Science.gov (United States)

    Chen, Cheng; Zhang, Qian; Xi, Zhi-jun; Li, Ning-chen; Jin, Jie; Zhang, Kai

    2011-03-01

    Postoperative pain is a common problem in male circumcision. We investigated the effect of nanometer silver dressing (Shenzhen AGT Pharm. Co. Ltd.) in relieving pain following male circumcision. Sixty patients undergoing circumcision in the outpatient department were randomized into an experimental and a control group, the incision covered with nanometer silver dressing in the former and with vaseline dressing in the latter. None of the patients received any analgesics or other pain-killing therapies after surgery. The postoperative pain intensity was accessed using the modified numeric pain intensity assessment scale at 1, 2, 3, 5 and 7 days after the operation, and statistical analyses were performed using SPSS 12.0 software. The patients averaged (31.13 +/- 13.94) years in age, and had no significant differences in age and body mass index (BMI) between the two groups. At 1, 2, 3 and 5 days, postoperative pain intensity was significantly lower in the experimental than in the control group (P > 0.05). Multiple regression analysis revealed that postoperative pain score was not correlated with patients' age, BMI and types of disease, but with the types of dressing. Nanometer silver dressing can significantly alleviate postoperative pain of circumcision, and is particularly applicable to such moist parts as the perineum, genitals, and urethra.

  14. High-fat Diet-induced Intestinal Hyperpermeability is Associated with Increased Bile Acids in the Large Intestine of Mice.

    Science.gov (United States)

    Murakami, Yuki; Tanabe, Soichi; Suzuki, Takuya

    2016-01-01

    Metabolic syndrome is characterized by low-grade chronic systemic inflammation, which is associated with intestinal hyperpermeability. This study examined the effects of 3 high-fat diets (HFDs) composed of different fat sources (soybean oil and lard) on the intestinal permeability, tight junction (TJ) protein expression, and cecal bile acid (BA) concentrations in mice, and then analyzed their interrelations. C57/BL6 mice were fed the control diet, HFD (soybean oil), HFD (lard), and HFD (mix; containing equal concentrations of soybean oil and lard) for 8 wk. Glucose tolerance, intestinal permeability, TJ protein expression, and cecal BA concentration were evaluated. Feeding with the 3 HDFs similarly increased body weight, liver weight, and fat pad weight, and induced glucose intolerance and intestinal hyperpermeability. The expression of TJ proteins, zonula occludens-2 and junctional adhesion molecule-A, were lower in the colons of the 3 HFD groups than in the control group (P acid and ω-muricholic acids, were detected (P < 0.05). These results suggest that the HFD-induced intestinal hyperpermeability is associated with increased BA secretion. The abundance of SBAs in the large intestine may be responsible for the hyperpermeability. © 2015 Institute of Food Technologists®

  15. Sinonasal inflammation in COPD

    DEFF Research Database (Denmark)

    Håkansson, Kåre; Konge, Lars; Thomsen, Sf

    2013-01-01

    In this review we demonstrate that patients with chronic obstructive pulmonary disease (COPD) frequently report sinonasal symptoms. Furthermore, we present evidence that smoking on its own can cause nasal disease, and that in COPD patients, nasal inflammation mimics that of the bronchi. All...... this evidence suggests that COPD related sinonasal disease does exist and that smoking on its own rather than systemic inflammation triggers the condition. However, COPD related sinonasal disease remains to be characterized in terms of symptoms and endoscopic findings. In addition, more studies are needed...... to quantify the negative impact of sinonasal symptoms on the quality of life in COPD patients....

  16. Natural resolution of inflammation.

    Science.gov (United States)

    Freire, Marcelo O; Van Dyke, Thomas E

    2013-10-01

    Inflammation is a protective response essential for maintaining human health and for fighting disease. As an active innate immune reaction to challenge, inflammation gives rise to clinical cardinal signs: rubor, calor, dolor, tumor and functio laesa. Termination of acute inflammation was previously recognized as a passive process; a natural decay of pro-inflammatory signals. We now understand that the natural resolution of inflammation involves well-integrated, active, biochemical programs that return tissues to homeostasis. This review focuses on recent advances in the understanding of the role of endogenous lipid mediators that modulate cellular fate and inflammation. Biosynthesis of eicosanoids and other lipids in exudates coincides with changes in the types of inflammatory cells. Resolution of inflammation is initiated by an active class switch in lipid mediators, such as classic prostaglandins and leukotrienes, to the production of proresolution mediators. Endogenous pro-resolving lipid mediators, including arachidonic acid-derived lipoxins, aspirin-triggered lipoxins, ω3-eicosapentaenoic acid-derived resolvins of the E-series, docosahexaenoic acid-derived resolvins of the D-series, protectins and maresins, are biosynthesized during the resolution phase of acute inflammation. Depending on the type of injury and the type of tissue, the initial cells that respond are polymorphonuclear leukocytes, monocytes/macrophages, epithelial cells or endothelial cells. The selective interaction of specific lipid mediators with G protein-coupled receptors expressed on innate immune cells (e.g. G protein-coupled receptor 32, lipoxin A4 receptor/formyl peptide receptor2, chemokine-like receptor 1, leukotriene B4 receptor type 1 and cabannoid receptor 2) induces cessation of leukocyte infiltration; vascular permeability/edema returns to normal with polymorphonuclear neutrophil death (mostly via apoptosis), the nonphlogistic infiltration of monocyte/macrophages and the removal

  17. Mechanisms of Body Weight Reduction and Metabolic Syndrome Alleviation by Tea

    Science.gov (United States)

    Yang, Chung S.; Zhang, Jinsong; Zhang, Le; Huang, Jinbao; Wang, Yijun

    2016-01-01

    Tea, a popular beverage made from leaves of the plant Camellia sinensis, has been shown to reduce body weight, alleviate metabolic syndrome, and prevent diabetes and cardiovascular diseases in animal models and humans. Such beneficial effects have generally been observed in most human studies when the level of tea consumption was 3 to 4 cups (600–900 mg tea catechins) or more per day. Green tea is more effective than black tea. In spite of numerous studies, the fundamental mechanisms for these actions still remain unclear. From a review of the literature, we propose that the two major mechanisms are: 1) decreasing absorption of lipids and proteins by tea constituents in the intestine, thus reducing calorie intake; and 2) activating AMPK by tea polyphenols that are bioavailable in the liver, skeletal muscle, and adipose tissues. The relative importance of these two mechanisms depends on the types of tea and diet consumed by individuals. The activated AMPK would decrease gluconeogenesis and fatty acid synthesis and increase catabolism, leading to body weight reduction and MetS alleviation. Other mechanisms and the health relevance of these beneficial effects of tea consumption remain to be further investigated. PMID:26577614

  18. Intestinal stromal cells in mucosal immunity and homeostasis.

    Science.gov (United States)

    Owens, B M J; Simmons, A

    2013-03-01

    A growing body of evidence suggests that non-hematopoietic stromal cells of the intestine have multiple roles in immune responses and inflammation at this mucosal site. Despite this, many still consider gut stromal cells as passive structural entities, with past research focused heavily on their roles in fibrosis, tumor progression, and wound healing, rather than their contributions to immune function. In this review, we discuss our current knowledge of stromal cells in intestinal immunity, highlighting the many immunological axes in which stromal cells have a functional role. We also consider emerging data that broaden the potential scope of their contribution to immunity in the gut and argue that these so-called "non-immune" cells are reclassified in light of their diverse contributions to intestinal innate immunity and the maintenance of mucosal homeostasis.

  19. Radioprotection of intestinal crypt cells by cox-inhibitors

    International Nuclear Information System (INIS)

    Bisnar, Paul O.; Dones, Rosa Angela S.A.; Serna, Paulene-Ver A.; Deocaris, Chester C.; Guttierez, Kalangitan V.; Deocaris, Custer C.

    2006-01-01

    The regulation of tissue homeostasis in the gastrointestinal epithelium after epithelial injury focuses on the prostaglandins(PGs) as its major mediators. The two cyclooxygenase isoforms, cox-1 and cox-2, catalyze synthesis of PGs. Cox-1 is the predominant cyclooxygenase isoform found in the normal intestine. In contrast, cox-2 is present at low levels in normal intestine but is elevated at sites of inflammation, and in adenomas and carcinomas. To study the effects of various commercially-available cox-inhibitors (Ketorolac: cox-1 selective; Celecoxib: cox-2 selective; and Indocid: cox-1/2 non-selective), we determine mouse crypt epithelial cell fate after genotoxic injury with whole-body gamma-ray exposure at 15 Gy. Intestinal tissues of mice treated with cox-2 inhibitors that showed invariable apoptotic event, however, have increased occurrence of regenerating cells. Our results suggest a potential application of cox-2 selective inhibitors as radioprotective agent for normal cells after radiotherapy. (Author)

  20. Retinoic acid suppresses intestinal mucus production and exacerbates experimental enterocolitis

    Directory of Open Access Journals (Sweden)

    Stefan H. Oehlers

    2012-07-01

    Exposure to retinoids for the treatment of acne has been linked to the etiology of inflammatory bowel disease (IBD. The intestinal mucus layer is an important structural barrier that is disrupted in IBD. Retinoid-induced alteration of mucus physiology has been postulated as a mechanism linking retinoid treatment to IBD; however, there is little direct evidence for this interaction. The zebrafish larva is an emerging model system for investigating the pathogenesis of IBD. Importantly, this system allows components of the innate immune system, including mucus physiology, to be studied in isolation from the adaptive immune system. This study reports the characterization of a novel zebrafish larval model of IBD-like enterocolitis induced by exposure to dextran sodium sulfate (DSS. The DSS-induced enterocolitis model was found to recapitulate several aspects of the zebrafish trinitrobenzene-sulfonic-acid (TNBS-induced enterocolitis model, including neutrophilic inflammation that was microbiota-dependent and responsive to pharmacological intervention. Furthermore, the DSS-induced enterocolitis model was found to be a tractable model of stress-induced mucus production and was subsequently used to identify a role for retinoic acid (RA in suppressing both physiological and pathological intestinal mucin production. Suppression of mucin production by RA increased the susceptibility of zebrafish larvae to enterocolitis when challenged with enterocolitic agents. This study illustrates a direct effect of retinoid administration on intestinal mucus physiology and, subsequently, on the progression of intestinal inflammation.

  1. Diagnosis of intestinal and extra intestinal amoebiasis

    International Nuclear Information System (INIS)

    Lopez, Myriam Consuelo; Quiroz, Damian Arnoldo; Pinilla, Analida Elizabeth

    2007-01-01

    The objective is to carry out a review of the national and international literature as of the XXth century in order to update the advances for the diagnosis of complex odd Entamoeba histolytic / Entamoeba dispar and that of intestinal and extra intestinal amoebiasis that may be of use to the scientific community. As well as to unify the diagnostic criteria of this parasitosis known as a public health problem, and as a consequence of that, optimize the quality of population care. Data source: there was a systematic search for the scientific literature Publisher in Spanish and English since 1960 until today, this selection started on the first semester of 2006 until 2007, in the development of the line on intestinal and extra-intestinal amoebiasis of the Medical School of the National University of Colombia. A retrospective search process was carried out, systematically reviewing the most relevant articles as well as the products of this research line. In deciding how to make this article, there was a continuous search in different data bases such as Medline, SciELO and other bases in the library of the National University of Colombia, as well as other classical books related to the subject. For that purpose the terms amoebiasis, odd Entamoeba histolytic, Entamoeba, diagnosis, epidemiology, dysentery, amoebic liver abscess, were used. Studies selection: titles and abstracts were reviewed to select the original publications and the most representative ones related to this article's subject. Data extraction: the articles were classified according to the subject, the chronology and the authors according to the scientific contribution to solve the problem. Synthesis of the data: in the fi rst instance, a chronological critical analysis was carried out to order and synthesize the progress made in the diagnosis until confirmation of the experts' agreements in the field of amoebiasis was obtained throughout the world. Conclusion: this article summarizes what has taken place

  2. HDAC1 and HDAC2 restrain the intestinal inflammatory response by regulating intestinal epithelial cell differentiation.

    Directory of Open Access Journals (Sweden)

    Naomie Turgeon

    Full Text Available Acetylation and deacetylation of histones and other proteins depends on histone acetyltransferases and histone deacetylases (HDACs activities, leading to either positive or negative gene expression. HDAC inhibitors have uncovered a role for HDACs in proliferation, apoptosis and inflammation. However, little is known of the roles of specific HDACs in intestinal epithelial cells (IEC. We investigated the consequences of ablating both HDAC1 and HDAC2 in murine IECs. Floxed Hdac1 and Hdac2 homozygous mice were crossed with villin-Cre mice. Mice deficient in both IEC HDAC1 and HDAC2 weighed less and survived more than a year. Colon and small intestinal sections were stained with hematoxylin and eosin, or with Alcian blue and Periodic Acid Schiff for goblet cell identification. Tissue sections from mice injected with BrdU for 2 h, 14 h and 48 h were stained with anti-BrdU. To determine intestinal permeability, 4-kDa FITC-labeled dextran was given by gavage for 3 h. Microarray analysis was performed on total colon RNAs. Inflammatory and IEC-specific gene expression was assessed by Western blot or semi-quantitative RT-PCR and qPCR with respectively total colon protein and total colon RNAs. HDAC1 and HDAC2-deficient mice displayed: 1 increased migration and proliferation, with elevated cyclin D1 expression and phosphorylated S6 ribosomal protein, a downstream mTOR target; 2 tissue architecture defects with cell differentiation alterations, correlating with reduction of secretory Paneth and goblet cells in jejunum and goblet cells in colon, increased expression of enterocytic markers such as sucrase-isomaltase in the colon, increased expression of cleaved Notch1 and augmented intestinal permeability; 3 loss of tissue homeostasis, as evidenced by modifications of claudin 3 expression, caspase-3 cleavage and Stat3 phosphorylation; 4 chronic inflammation, as determined by inflammatory molecular expression signatures and altered inflammatory gene expression

  3. Ex vivo culture of intestinal crypt organoids as a model system for assessing cell death induction in intestinal epithelial cells and enteropathy

    NARCIS (Netherlands)

    Grabinger, T.; Luks, L.; Kostadinova, F.; Zimberlin, C.; Medema, J. P.; Leist, M.; Brunner, T.

    2014-01-01

    Intestinal epithelial cells (IECs) not only have a critical function in the absorption of nutrients, but also act as a physical barrier between our body and the outside world. Damage and death of the epithelial cells lead to the breakdown of this barrier function and inflammation due to access of

  4. Arctigenin alleviates ER stress via activating AMPK

    Science.gov (United States)

    Gu, Yuan; Sun, Xiao-xiao; Ye, Ji-ming; He, Li; Yan, Shou-sheng; Zhang, Hao-hao; Hu, Li-hong; Yuan, Jun-ying; Yu, Qiang

    2012-01-01

    Aim: To investigate the protective effects of arctigenin (ATG), a phenylpropanoid dibenzylbutyrolactone lignan from Arctium lappa L (Compositae), against ER stress in vitro and the underlying mechanisms. Methods: A cell-based screening assay for ER stress regulators was established. Cell viability was measured using MTT assay. PCR and Western blotting were used to analyze gene and protein expression. Silencing of the CaMKKβ, LKB1, and AMPKα1 genes was achieved by RNA interference (RNAi). An ATP bioluminescent assay kit was employed to measure the intracellular ATP levels. Results: ATG (2.5, 5 and 10 μmol/L) inhibited cell death and unfolded protein response (UPR) in a concentration-dependent manner in cells treated with the ER stress inducer brefeldin A (100 nmol/L). ATG (1, 5 and 10 μmol/L) significantly attenuated protein synthesis in cells through inhibiting mTOR-p70S6K signaling and eEF2 activity, which were partially reversed by silencing AMPKα1 with RNAi. ATG (1-50 μmol/L) reduced intracellular ATP level and activated AMPK through inhibiting complex I-mediated respiration. Pretreatment of cells with the AMPK inhibitor compound C (25 μmol/L) rescued the inhibitory effects of ATG on ER stress. Furthermore, ATG (2.5 and 5 μmol/L) efficiently activated AMPK and reduced the ER stress and cell death induced by palmitate (2 mmol/L) in INS-1 β cells. Conclusion: ATG is an effective ER stress alleviator, which protects cells against ER stress through activating AMPK, thus attenuating protein translation and reducing ER load. PMID:22705729

  5. Why may allopregnanolone help alleviate loneliness?

    Science.gov (United States)

    Cacioppo, S; Cacioppo, J T

    2015-12-01

    Impaired biosynthesis of Allopregnanolone (ALLO), a brain endogenous neurosteroid, has been associated with numerous behavioral dysfunctions, which range from anxiety- and depressive-like behaviors to aggressive behavior and changes in responses to contextual fear conditioning in rodent models of emotional dysfunction. Recent animal research also demonstrates a critical role of ALLO in social isolation. Although there are likely aspects of perceived social isolation that are uniquely human, there is also continuity across species. Both human and animal research show that perceived social isolation (which can be defined behaviorally in animals and humans) has detrimental effects on physical health, such as increased hypothalamic pituitary adrenal (HPA) activity, decreased brain-derived neurotrophic factor (BDNF) expression, and increased depressive behavior. The similarities between animal and human research suggest that perceived social isolation (loneliness) may also be associated with a reduction in the synthesis of ALLO, potentially by reducing BDNF regulation and increasing HPA activity through the hippocampus, amygdala, and bed nucleus of the stria terminalis (BNST), especially during social threat processing. Accordingly, exogenous administration of ALLO (or ALLO precursor, such as pregnenolone), in humans may help alleviate loneliness. Congruent with our hypothesis, exogenous administration of ALLO (or ALLO precursors) in humans has been shown to improve various stress-related disorders that show similarities between animals and humans i.e., post-traumatic stress disorders, traumatic brain injuries. Because a growing body of evidence demonstrates the benefits of ALLO in socially isolated animals, we believe our ALLO hypothesis can be applied to loneliness in humans, as well. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Inflammation, Immunity, and Hypertension.

    Science.gov (United States)

    Agita, Arisya; Alsagaff, M Thaha

    2017-04-01

    The immune system, inflammation and hypertension are related to each other. Innate and adaptive immunity system triggers an inflammatory process, in which blood pressure may increase, stimulating organ damage. Cells in innate immune system produce ROS, such as superoxide and hydrogen peroxide, which aimed at killing pathogens. Long-term inflammation process increases ROS production, causing oxidative stress which leads to endothelial dysfunction. Endothelial function is to regulate blood vessel tone and structure. When inflammation lasts, NO bioavailability decreases, disrupting its main function as vasodilator, so that blood vessels relaxation and vasodilatation are absent. Effector T cells and regulatory lymphocytes, part of the adaptive immune system, plays role in blood vessels constriction in hypertension. Signals from central nervous system and APC activates effector T lymphocyte differentiation and accelerate through Th-1 and Th-17 phenotypes. Th-1 and Th-17 effectors participate in inflammation which leads to increased blood pressure. One part of CD4+ is the regulatory T cells (Tregs) that suppress immune response activation as they produce immunosuppressive cytokines, such as TGF-β and IL-10. Adoptive transfer of Tregs cells can reduce oxidative stress in blood vessels, endothelial dysfunction, infiltration of aortic macrophages and T cells as well as proinflammatory cytokine levels in plasma circulation.

  7. Inflammation, Immunity, and Hypertension

    Directory of Open Access Journals (Sweden)

    Arisya Agita

    2017-04-01

    Full Text Available The immune system, inflammation and hypertension are related to each other. Innate and adaptive immunity system triggers an inflammatory process, in which blood pressure may increase, stimulating organ damage. Cells in innate immune system produce ROS, such as superoxide and hydrogen peroxide, which aimed at killing pathogens. Long-term inflammation process increases ROS production, causing oxidative stress which leads to endothelial dysfunction. Endothelial function is to regulate blood vessel tone and structure. When inflammation lasts, NO bioavailability decreases, disrupting its main function as vasodilator, so that blood vessels relaxation and vasodilatation are absent. Effector T cells and regulatory lymphocytes, part of the adaptive immune system, plays role in blood vessels constriction in hypertension. Signals from central nervous system and APC activates effector T lymphocyte differentiation and accelerate through Th-1 and Th-17 phenotypes. Th-1 and Th-17 effectors participate in inflammation which leads to increased blood pressure. One part of CD4+ is the regulatory T cells (Tregs that suppress immune response activation as they produce immunosuppressive cytokines, such as TGF-β and IL-10. Adoptive transfer of Tregs cells can reduce oxidative stress in blood vessels, endothelial dysfunction, infiltration of aortic macrophages and T cells as well as proinflammatory cytokine levels in plasma circulation.

  8. CNS and inflammation

    African Journals Online (AJOL)

    EL-HAKIM

    overproduction8. The most intense interest in inflammation in the. CNS has arisen from its potential role in diseases including acute brain injury, stroke, epilepsy, multiple sclerosis, motor neurone disease, movement disorders, and more recently some psychiatric disorders such as depression, anxiety and schizophrenia.

  9. Inflammation and Alzheimer's disease

    NARCIS (Netherlands)

    Akiyama, H.; Barger, S.; Barnum, S.; Bradt, B.; Bauer, J.; Cole, G. M.; Cooper, N. R.; Eikelenboom, P.; Emmerling, M.; Fiebich, B. L.; Finch, C. E.; Frautschy, S.; Griffin, W. S.; Hampel, H.; Hull, M.; Landreth, G.; Lue, L.; Mrak, R.; Mackenzie, I. R.; McGeer, P. L.; O'Banion, M. K.; Pachter, J.; Pasinetti, G.; Plata-Salaman, C.; Rogers, J.; Rydel, R.; Shen, Y.; Streit, W.; Strohmeyer, R.; Tooyoma, I.; van Muiswinkel, F. L.; Veerhuis, R.; Walker, D.; Webster, S.; Wegrzyniak, B.; Wenk, G.; Wyss-Coray, T.

    2000-01-01

    Inflammation clearly occurs in pathologically vulnerable regions of the Alzheimer's disease (AD) brain, and it does so with the full complexity of local peripheral inflammatory responses. In the periphery, degenerating tissue and the deposition of highly insoluble abnormal materials are classical

  10. Glucocorticoids and chronic inflammation.

    Science.gov (United States)

    Straub, Rainer H; Cutolo, Maurizio

    2016-12-01

    Glucocorticoids are steroid hormones that once bound to their receptor interact with the DNA binding domain. Almost 1000-2000 genes are sensitive to their effects, including immune/inflammatory response genes. However, their role in pathophysiology and therapy is still debated. We performed a literature survey using the key words glucocorticoids, inflammation, autoimmune disease, rheumatology and adrenal glands in order to define important targets for this review on glucocorticoids. Considering endogenous/exogenous glucocorticoids in chronic inflammatory diseases brought up five major points for discussion: inadequately low production of endogenous cortisol relative to systemic inflammation (the disproportion principle); changes of the systemic and local cortisol-to-cortisone shuttle (reactivation and degradation of cortisol); inflammation-induced glucocorticoid resistance; highlights of present glucocorticoid therapy; and the role of circadian rhythms in action of cortisol. Much of this information becomes understandable in the context of neurohormonal energy regulation as recently summarized. The optimization of long-term low-dose glucocorticoid therapy in chronic inflammatory diseases arises from the understanding of the above mentioned aspects. Since glucocorticoid resistance is a consequence of inflammation, adequate anti-inflammatory therapy is mandatory. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  11. Immunsystemet ved kronisk inflammation

    DEFF Research Database (Denmark)

    Bendtzen, Klaus

    2008-01-01

    Innate and adaptive immunity has evolved as a defence against infections and as an important repair mechanism after physical injury. If elimination of microbes and healing is not achieved, or if the immune system is dysregulated, chronic inflammation ensues. Immune cells become engaged in prolonged...

  12. Idiopathic granulomatous orbital inflammation

    NARCIS (Netherlands)

    Mombaerts, I.; Schlingemann, R. O.; Goldschmeding, R.; Koornneef, L.

    1996-01-01

    PURPOSE: Granulomatous orbital inflammation may occur as an isolated condition of unknown origin. These idiopathic granulomatous lesions are believed to belong to the orbital pseudotumor group by some authors, whereas others consider them sarcoidosis limited to the orbit. The aim of this study is to

  13. Cytokines and intraocular inflammation

    NARCIS (Netherlands)

    Hoekzema, R.; Murray, P. I.; Kijlstra, A.

    1990-01-01

    Although new endogenous mediators of inflammatory and immune responses are reported almost on a monthly basis, the cytokines IL-1, TNF, and IL-6 have emerged as the primary regulators of local inflammation in man. In this paper, uveitogenic and other properties of these particular cytokines are

  14. Intestinal anisakidosis (anisakiosis).

    Science.gov (United States)

    Takei, Hidehiro; Powell, Suzanne Z

    2007-10-01

    A case of intestinal anisakidosis in a 42-year-old man in Japan is presented. His chief complaint was an acute onset of severe abdominal pain. Approximately 12 hours before the onset of this symptom, he had eaten sliced raw mackerel ("sashimi"). Upper endoscopy was unremarkable. At exploratory laparotomy, an edematous, diffusely thickened segment of jejunum was observed, which was resected. The postoperative course was uneventful. The segment of small intestine showed a granular indurated area on the mucosal surface, and microscopically, a helminthic larva penetrating the intestinal wall, which was surrounded by a cuff of numerous neutrophils and eosinophils, as well as diffuse acute serositis. A cross section of the larva revealed the internal structures, pathognomonic of Anisakis simplex. Although anisakidosis is rare in the United States, with the increasing popularity of Japanese cuisine, the incidence is expected to increase, and pathologists should be familiar with this disease.

  15. Intestinal failure: a review

    Science.gov (United States)

    Allan, Philip; Lal, Simon

    2018-01-01

    Intestinal failure (IF) is the inability of the gut to absorb necessary water, macronutrients (carbohydrate, protein, and fat), micronutrients, and electrolytes sufficient to sustain life and requiring intravenous supplementation or replacement. Acute IF (types 1 and 2) is the initial phase of the illness and may last for weeks to a few months, and chronic IF (type 3) from months to years. The challenge of caring for patients with IF is not merely the management of the underlying condition leading to IF or the correct provision of appropriate nutrition or both but also the prevention of complications, whether thromboembolic phenomenon (for example, venous occlusion), central venous catheter-related bloodstream infection, IF-associated liver disease, or metabolic bone disease. This review looks at recent questions regarding chronic IF (type 3), its diagnosis and management, the role of the multidisciplinary team, and novel therapies, including hormonal treatment for short bowel syndrome but also surgical options for intestinal lengthening and intestinal transplant. PMID:29399329

  16. Small intestine diverticuli

    International Nuclear Information System (INIS)

    Pomakov, P.; Risov, A.

    1991-01-01

    The routine method of contrast matter passage applied to 850 patients with different gastrointestinal diseases proved inefficient to detect any small-intestinal diverticuli. The following modiffications of the method have been tested in order to improve the diagnostic possibilities of the X-ray: study at short intervals, assisted passage, enteroclysm, pharmacodynamic impact, retrograde filling of the ileum by irrigoscopy. Twelve diverticuli of the small-intestinal loops were identified: 5 Meckel's diverticuli, 2 solitary of which one of the therminal ileum, 2 double diverticuli and 1 multiple diverticulosis of the jejunum. The results show that the short interval X-ray examination of the small intestines is the method of choice for identifying local changes in them. The solitary diverticuli are not casuistic scarcity, its occurrence is about 0.5% at purposeful X-ray investigation. The assisted passage method is proposed as a method of choice for detection of the Meckel's diverticulum. 5 figs., 3 tabs. 18 refs

  17. Chronic intestinal pseudoobstruction syndrome

    International Nuclear Information System (INIS)

    Yeon, Kyung Mo; Seo, Jeong Kee; Lee, Yong Seok

    1992-01-01

    Chronic intestinal pseudoobstruction syndrome is a rare clinical condition in which impaired intestinal peristalsis causes recurrent symptoms of bowel obstruction in the absence of a mechanical occlusion. This syndrome may involve variable segments of small or large bowel, and may be associated with urinary bladder retention. This study included 6 children(3 boys and 3 girls) of chronic intestinal obstruction. Four were symptomatic at birth and two were of the ages of one month and one year. All had abdominal distension and deflection difficulty. Five had urinary bladder distension. Despite parenteral nutrition and surgical intervention(ileostomy or colostomy), bowel obstruction persisted and four patients expired from sepses within one year. All had gaseous distension of small and large bowel on abdominal films. In small bowel series, consistent findings were variable degree of dilatation, decreased peristalsis(prolonged transit time) and microcolon or microrectum. This disease entity must be differentiated from congenital megacolon, ileal atresia and megacystis syndrome

  18. Small Intestinal Infections.

    Science.gov (United States)

    Munot, Khushboo; Kotler, Donald P

    2016-06-01

    Small intestinal infections are extremely common worldwide. They may be bacterial, viral, or parasitic in etiology. Most are foodborne or waterborne, with specific etiologies differing by region and with diverse pathophysiologies. Very young, very old, and immune-deficient individuals are the most vulnerable to morbidity or mortality from small intestinal infections. There have been significant advances in diagnostic sophistication with the development and early application of molecular diagnostic assays, though these tests have not become mainstream. The lack of rapid diagnoses combined with the self-limited nature of small intestinal infections has hampered the development of specific and effective treatments other than oral rehydration. Antibiotics are not indicated in the absence of an etiologic diagnosis, and not at all in the case of some infections.

  19. ADAM12 alleviates the skeletal muscle pathology in mdx dystrophic mice

    DEFF Research Database (Denmark)

    Kronqvist, Pauliina; Kawaguchi, Nobuko; Albrechtsen, Reidar

    2002-01-01

    we examined the role of the transmembrane ADAM12, a disintegrin and metalloprotease, which is normally associated with development and regeneration of skeletal muscle. We demonstrate that ADAM12 overexpression in the dystrophin-deficient mdx mice alleviated the muscle pathology in these animals......Muscular dystrophy is characterized by muscle degeneration and insufficient regeneration and replacement of muscle fibers by connective tissue. New therapeutic strategies directed toward various forms of muscular dystrophy are needed to preserve muscle mass and promote regeneration. In this study......, as evidenced by less muscle cell necrosis and inflammation, lower levels of serum creatine kinase, and less uptake of Evans Blue dye into muscle fibers. These studies demonstrate that ADAM12 directly or indirectly contributes to muscle cell regeneration, stability, and survival....

  20. Maintenance of a healthy trajectory of the intestinal microbiome during aging: a dietary approach.

    Science.gov (United States)

    Candela, Marco; Biagi, Elena; Brigidi, Patrizia; O'Toole, Paul W; De Vos, Willem M

    2014-01-01

    Sharing an intense transgenomic metabolism with the host, the intestinal microbiota is an essential factor for several aspects of the human physiology. However, several age-related factors, such as changes diet, lifestyle, inflammation and frailty, force the deterioration of this intestinal microbiota-host mutualistic interaction, compromising the possibility to reach longevity. In this scenario, the NU-AGE project involves the development of dietary interventions specifically tailored to the maintenance of a healthy trajectory of the intestinal microbiome, counteracting all processes connected to the pathophysiology of the human aging. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  1. The intestinal calcistat

    Directory of Open Access Journals (Sweden)

    M K Garg

    2013-01-01

    Full Text Available The main physiological function of vitamin D is maintenance of calcium homeostasis by its effect on calcium absorption, and bone health in association with parathyroid gland. Vitamin D deficiency (VDD is defined as serum 25-hydroxy vitamin D (25OHD levels <20 ng/ml. Do all subjects with VDD have clinical disease according to this definition? We hypothesize that there exist an intestinal calcistat, which controls the calcium absorption independent of PTH levels. It consists of calcium sensing receptor (CaSR on intestinal brush border, which senses calcium in intestinal cells and vitamin D system in intestinal cells. CaSR dampens the generation of active vitamin D metabolite in intestinal cells and decrease active transcellular calcium transport. It also facilitates passive paracellular diffusion of calcium in intestine. This local adaptation adjusts the fractional calcium absorption according the body requirement. Failure of local adaptation due to decreased calcium intake, decreased supply of 25OHD, mutation in CaSR or vitamin D system decreases systemic calcium levels and systemic adaptations comes into the play. Systemic adaptations consist of rise in PTH and increase in active vitamin D metabolites. These adaptations lead to bone resorption and maintenance of calcium homeostasis. Not all subjects with varying levels of VDD manifest with secondary hyperparathyroidism and decreased in bone mineral density. We suggest that rise in PTH is first indicator of VDD along with decrease in BMD depending on duration of VDD. Hence, subjects with any degree of VDD with normal PTH and BMD should not be labeled as vitamin D deficient. These subjects can be called subclinical VDD, and further studies are required to assess beneficial effect of vitamin D supplementation in this subset of population.

  2. inflammation and iron metabolism

    Directory of Open Access Journals (Sweden)

    A Dzedzej

    2016-08-01

    Full Text Available Following acute physical activity, blood hepcidin concentration appears to increase in response to exercise-induced inflammation, but the long-term impact of exercise on hepcidin remains unclear. Here we investigated changes in hepcidin and the inflammation marker interleukin-6 to evaluate professional basketball players’ response to a season of training and games. The analysis also included vitamin D (25(OHD3 assessment, owing to its anti-inflammatory effects. Blood samples were collected for 14 players and 10 control non-athletes prior to and after the 8-month competitive season. Athletes’ performance was assessed with the NBA efficiency score. At the baseline hepcidin correlated with blood ferritin (r=0.61; 90% CL ±0.31, but at the end of the season this correlation was absent. Compared with the control subjects, athletes experienced clear large increases in hepcidin (50%; 90% CI 15-96% and interleukin-6 (77%; 90% CI 35-131% and a clear small decrease in vitamin D (-12%; 90% CI -20 to -3% at the season completion. Correlations between change scores of these variables were unclear (r = -0.21 to 0.24, 90% CL ±0.5, but their uncertainty generally excluded strong relationships. Athletes were hence concluded to have experienced acute inflammation at the beginning but chronic inflammation at the end of the competitive season. At the same time, the moderate correlation between changes in vitamin D and players’ performance (r=0.43 was suggestive of its beneficial influence. Maintaining the appropriative concentration of vitamin D is thus necessary for basketball players’ performance and efficiency. The assessment of hepcidin has proven to be useful in diagnosing inflammation in response to chronic exercise.

  3. Vasoactive Intestinal Peptide Nanomedicine for the Management of Inflammatory Bowel Disease.

    Science.gov (United States)

    Jayawardena, Dulari; Anbazhagan, Arivarasu N; Guzman, Grace; Dudeja, Pradeep K; Onyuksel, Hayat

    2017-11-06

    Inflammatory bowel disease (IBD) is a chronic relapsing disorder of the intestine, with increasing incidence worldwide. At present, the management of IBD is an unmet medical need due to the ineffectiveness of currently available drugs in treating all patients, and there is strong demand for novel therapeutics. In this regard, vasoactive intestinal peptide, a potent anti-inflammatory endogenous hormone, has shown promise in managing multiple immune disorders in animal models. However, when administered in the free form, VIP undergoes rapid degradation in vivo, and with continuous infusion, it causes severe dose limiting side effects. To overcome these barriers, we have developed a superior mode to deliver VIP in its native form, using sterically stabilized micelles (VIP-SSM). Our previous studies demonstrated that, VIP, when administered in SSM, prevented joint damage and inflammation in a mouse model of rheumatoid arthritis at a significantly lower dose than the free peptide, completely abrogating the serious side effect of hypotension associated with VIP. In the current study, we demonstrate the therapeutic benefit of VIP-SSM over free peptide in reversing severe colitis associated with IBD. First, we conducted preliminary studies with dextran sulfate sodium (DSS) induced colitis in mice, to determine the effectiveness of VIP administered on alternate days in reducing disease severity. Thereafter, a single intra peritoneal injection of VIP-SSM or the free peptide was used to determine its therapeutic effect on the reversal of colitis and associated diarrhea. The results demonstrated that when administered on alternate days, both VIP-SSM and VIP were capable of alleviating DSS colitis in mice. However, when administered as a single dose, in a therapeutic setting, VIP-SSM showed superior benefits compared to the free peptide in ameliorating colitis phenotype. Namely, the loss of solid fecal pellets and increased fluid accumulation in colon resulting from DSS insult

  4. Inflammation: depression fans the flames and feasts on the heat.

    Science.gov (United States)

    Kiecolt-Glaser, Janice K; Derry, Heather M; Fagundes, Christopher P

    2015-11-01

    Depression and inflammation fuel one another. Inflammation plays a key role in depression's pathogenesis for a subset of depressed individuals; depression also primes larger cytokine responses to stressors and pathogens that do not appear to habituate. Accordingly, treatment decisions may be informed by attention to questions of how (pathways) and for whom (predispositions) these links exist, which are the focus of this article. When combined with predisposing factors (moderators such as childhood adversity and obesity), stressors and pathogens can lead to exaggerated or prolonged inflammatory responses. The resulting sickness behaviors (e.g., pain, disturbed sleep), depressive symptoms, and negative health behaviors (e.g., poor diet, a sedentary lifestyle) may act as mediating pathways that lead to further, unrestrained inflammation and depression. Depression, childhood adversity, stressors, and diet can all influence the gut microbiome and promote intestinal permeability, another pathway to enhanced inflammatory responses. Larger, more frequent, or more prolonged inflammatory responses could have negative mental and physical health consequences. In clinical practice, inflammation provides a guide to potential targets for symptom management by signaling responsiveness to certain therapeutic strategies. For example, a theme across research with cytokine antagonists, omega-3 fatty acids, celecoxib, and exercise is that anti-inflammatory interventions have a substantially greater impact on mood in individuals with heightened inflammation. Thus, when inflammation and depression co-occur, treating them in tandem may enhance recovery and reduce the risk of recurrence. The bidirectional links between depression, inflammation, and disease suggest that effective depression treatments could have a far-reaching impact on mood, inflammation, and health.

  5. Dipotassium Glycyrrhizate Inhibits HMGB1-Dependent Inflammation and Ameliorates Colitis in Mice.

    Directory of Open Access Journals (Sweden)

    Roberta Vitali

    Full Text Available High mobility group box-1 (HMGB1 is a DNA-binding protein that is released from injured cells during inflammation. Advances in targeting HMGB1 represent a major challenge to improve the treatment of acute/chronic inflammation.This study is aimed at verifying whether the inhibition of HMGB1 through dipotassium glycyrrhizate (DPG is a good strategy to reduce intestinal inflammation.Human colon adenocarcinoma cell line, HT29, human epithelial colorectal adenocarcinoma, Caco2, and murine macrophage cell line, RAW 264.7, were cultured to investigate the effect of DPG on the secretion of HMGB1. Acute colitis was induced in C57BL/6 mice through administration of 3% dextran sodium sulphate (DSS; a combined treatment with DSS and 3 or 8 mg/kg/day DPG was used to investigate the effects of DPG on intestinal inflammation. Animals were euthanized at seventh day and colonic samples underwent molecular and histological analyses.DPG significantly reduces in vitro the release of HMGB1 in the extracellular matrix as well as expression levels of pro-inflammatory cytokines, TNF-alpha, IL-1beta and IL-6, by inhibiting HMGB1. Moreover, DPG significantly decreases the severity of DSS-induced colitis in mice. Murine colonic samples show decreased mRNA levels of pro-inflammatory cytokines TNF-alpha, IL-1beta and IL-6, as well as HMGB1 receptors, RAGE and TLR4. Finally, HMGB1, abundantly present in the feces of mice with DSS-induced colitis, is strongly reduced by DPG.HMGB1 is an early pro-inflammatory cytokine and an active protagonist of mucosal gut inflammation. DPG exerts inhibitory effects against HMGB1 activity, significantly reducing intestinal inflammation. Thus, we reason that DPG could represent an innovative tool for the management of human intestinal inflammation.

  6. Small intestine aspirate and culture

    Science.gov (United States)

    ... ency/article/003731.htm Small intestine aspirate and culture To use the sharing features on this page, please enable JavaScript. Small intestine aspirate and culture is a lab test to check for infection ...

  7. Alleviation of Carbon-Tetrachloride-Induced Liver Injury and Fibrosis by Betaine Supplementation in Chickens.

    Science.gov (United States)

    Tsai, Meng-Tsz; Chen, Ching-Yi; Pan, Yu-Hui; Wang, Siou-Huei; Mersmann, Harry J; Ding, Shih-Torng

    2015-01-01

    Betaine is a food component with well-reported hepatoprotection effects. However, the effects and mechanisms of betaine on liver fibrosis development are still insufficient. Because metabolic functions of chicken and human liver is similar, we established a chicken model with carbon Tetrachloride- (CCl4-) induced fibrosis for studying antifibrotic effect of betaine in vivo and in vitro. Two-week-old male chicks were supplemented with betaine (1%, w/v) in drinking water for 2 weeks prior to the initiation of CCl4 treatment (i.p.) until sacrifice. Primary chicken hepatocytes were treated with CCl4 and betaine to mimic the in vivo supplementation. The supplementation of betaine significantly alleviated liver fibrosis development along with the inhibition of lipid peroxidation, hepatic inflammation cytokine, and transforming growth factor-β1 expression levels. These inhibitive effects were also accompanied with the attenuation of hepatic stellate cell activation. Furthermore, our in vitro studies confirmed that betaine provides antioxidant capacity for attenuating the hepatocyte necrosis by CCl4. Altogether, our results highlight the antioxidant ability of betaine, which alleviates CCl4-induced fibrogenesis process along with the suppression of hepatic stellate cells activation. Since betaine is a natural compound without toxicity, we suggest betaine can be used as a potent nutritional or therapeutic factor for reducing liver fibrosis.

  8. Alleviation of Carbon-Tetrachloride-Induced Liver Injury and Fibrosis by Betaine Supplementation in Chickens

    Directory of Open Access Journals (Sweden)

    Meng-Tsz Tsai

    2015-01-01

    Full Text Available Betaine is a food component with well-reported hepatoprotection effects. However, the effects and mechanisms of betaine on liver fibrosis development are still insufficient. Because metabolic functions of chicken and human liver is similar, we established a chicken model with carbon Tetrachloride- (CCl4- induced fibrosis for studying antifibrotic effect of betaine in vivo and in vitro. Two-week-old male chicks were supplemented with betaine (1%, w/v in drinking water for 2 weeks prior to the initiation of CCl4 treatment (i.p. until sacrifice. Primary chicken hepatocytes were treated with CCl4 and betaine to mimic the in vivo supplementation. The supplementation of betaine significantly alleviated liver fibrosis development along with the inhibition of lipid peroxidation, hepatic inflammation cytokine, and transforming growth factor-β1 expression levels. These inhibitive effects were also accompanied with the attenuation of hepatic stellate cell activation. Furthermore, our in vitro studies confirmed that betaine provides antioxidant capacity for attenuating the hepatocyte necrosis by CCl4. Altogether, our results highlight the antioxidant ability of betaine, which alleviates CCl4-induced fibrogenesis process along with the suppression of hepatic stellate cells activation. Since betaine is a natural compound without toxicity, we suggest betaine can be used as a potent nutritional or therapeutic factor for reducing liver fibrosis.

  9. Regulation of intestinal immune responses through TLR activation: implications for pro- and prebiotics

    Directory of Open Access Journals (Sweden)

    Sander eDe Kivit

    2014-02-01

    Full Text Available The intestinal mucosa is constantly facing a high load of antigens including bacterial antigens derived from the microbiota and food. Despite this, the immune cells present in the gastrointestinal tract do not initiate a pro-inflammatory immune response. Toll-like receptors (TLRs are pattern recognition receptors expressed by various cells in the gastrointestinal tract, including intestinal epithelial cells (IEC and resident immune cells in the lamina propria. Many diseases, including chronic intestinal inflammation (e.g. inflammatory bowel disease, irritable bowel syndrome (IBS, allergic gastroenteritis (e.g. eosinophilic gastroenteritis and allergic IBS and infections are nowadays associated with a deregulated microbiota. The microbiota may directly interact with TLR. In addition, differences in intestinal TLR expression in health and disease may suggest that TLR play an essential role in disease pathogenesis and may be novel targets for therapy. TLR signaling in the gut is involved in either maintaining intestinal homeostasis or the induction of an inflammatory response. This mini review provides an overview of the current knowledge regarding the contribution of intestinal epithelial TLR signaling in both tolerance induction or promoting intestinal inflammation, with a focus on food allergy. We will also highlight a potential role of the microbiota in regulating gut immune responses, especially through TLR activation.

  10. RHOA GTPase Controls YAP-Mediated EREG Signaling in Small Intestinal Stem Cell Maintenance

    Directory of Open Access Journals (Sweden)

    Ming Liu

    2017-12-01

    Full Text Available Summary: RHOA, a founding member of the Rho GTPase family, is critical for actomyosin dynamics, polarity, and morphogenesis in response to developmental cues, mechanical stress, and inflammation. In murine small intestinal epithelium, inducible RHOA deletion causes a loss of epithelial polarity, with disrupted villi and crypt organization. In the intestinal crypts, RHOA deficiency results in reduced cell proliferation, increased apoptosis, and a loss of intestinal stem cells (ISCs that mimic effects of radiation damage. Mechanistically, RHOA loss reduces YAP signaling of the Hippo pathway and affects YAP effector epiregulin (EREG expression in the crypts. Expression of an active YAP (S112A mutant rescues ISC marker expression, ISC regeneration, and ISC-associated Wnt signaling, but not defective epithelial polarity, in RhoA knockout mice, implicating YAP in RHOA-regulated ISC function. EREG treatment or active β-catenin Catnblox(ex3 mutant expression rescues the RhoA KO ISC phenotypes. Thus, RHOA controls YAP-EREG signaling to regulate intestinal homeostasis and ISC regeneration. : In this article, Zheng and colleagues show that inducible RHOA deletion in mice causes defects in intestine epithelial polarity and deficiencies in intestinal stem cell proliferation, survival, and regeneration. They further demonstrate by genetic rescues that RHOA controls a YAP-EREG axis to mediate canonical Wnt signaling, intestinal stem cell function, and intestinal homeostasis. Keywords: mouse model, intestinal stem cell, regeneration, Rho GTPase, RhoA, Hippo signaling, YAP, Wnt signaling

  11. Escin: inhibiting inflammation and promoting gastrointestinal transit to attenuate formation of postoperative adhesions.

    Science.gov (United States)

    Fu, Fenghua; Hou, Yuezhi; Jiang, Wanglin; Wang, Ronghua; Liu, Ke

    2005-12-01

    Postoperative peritoneal adhesions are common, serious complications of general abdominal and gynecologic surgery that can lead to chronic abdominal pain, intestinal obstruction, and infertility. As yet, there are no ideal drugs that may be prescribed for patients to prevent adhesion formation effectively. In this study the effects of escin, a natural drug, on the various steps of adhesion formation were investigated. The effects of escin on increased vascular permeability induced by acetic acid in a mouse model of acute inflammation, granuloma formation in a subchronic inflammatory rat model, gastrointestinal transit in rats with intestinal paralysis, intestinal motility in postoperative patients, and postoperative adhesion formation in a rat model were observed. It was shown that escin could inhibit acute inflammation and granuloma formation, cause acceleration of gastrointestinal transit, help recover intestinal motility, and attenuate the formation of postoperative adhesions. The findings suggest that escin attenuates the formation of postoperative adhesions by inhibiting inflammation and promoting gastrointestinal transit. Thus it may be concluded that both inhibition of inflammation and increased gastrointestinal motility during the early postoperative period have a positive effect on decreasing the formation of adhesions.

  12. Stress induces endotoxemia and low-grade inflammation by increasing barrier permeability

    Directory of Open Access Journals (Sweden)

    Karin ede Punder

    2015-05-01

    Full Text Available Chronic non-communicable diseases (NCDs are the leading causes of work absence, disability and mortality worldwide. Most of these diseases are associated with low-grade inflammation. Here we hypothesize that stresses (defined as homeostatic disturbances can induce low-grade inflammation by increasing the availability of water, sodium and energy-rich substances to meet the increased metabolic demand induced by the stressor. One way of triggering low-grade inflammation is by increasing intestinal barrier permeability through activation of various components of the stress system. Although beneficial to meet the demands necessary during stress, increased intestinal barrier permeability also raises the possibility of the translocation of bacteria and their toxins across the intestinal lumen into the blood circulation. In combination with modern life-style factors, the increase in bacteria/bacterial toxin translocation arising from a more permeable intestinal wall causes a low-grade inflammatory state. We support this hypothesis with numerous studies finding associations with NCDs and markers of endotoxemia, suggesting that this process plays a pivotal and perhaps even a causal role in the development of low-grade inflammation and its related diseases.

  13. NOD2 and inflammation: current insights

    Directory of Open Access Journals (Sweden)

    Negroni A

    2018-02-01

    Full Text Available Anna Negroni,1 Maria Pierdomenico,2 Salvatore Cucchiara,2 Laura Stronati3 1Division of Health Protection Technologies, Territorial and Production Systems Sustainability Department, ENEA, Rome, Italy; 2Department of Pediatrics and Infantile Neuropsychiatry, Pediatric Gastroenterology and Liver Unit, Sapienza University of Rome, Rome, Italy; 3Department of Cellular Biotechnology and Hematology, Sapienza University of Rome, Rome, Italy Abstract: The nucleotide-binding oligomerization domain (NOD protein, NOD2, belonging to the intracellular NOD-like receptor family, detects conserved motifs in bacterial peptidoglycan and promotes their clearance through activation of a proinflammatory transcriptional program and other innate immune pathways, including autophagy and endoplasmic reticulum stress. An inactive form due to mutations or a constitutive high expression of NOD2 is associated with several inflammatory diseases, suggesting that balanced NOD2 signaling is critical for the maintenance of immune homeostasis. In this review, we discuss recent developments about the pathway and mechanisms of regulation of NOD2 and illustrate the principal functions of the gene, with particular emphasis on its central role in maintaining the equilibrium between intestinal microbiota and host immune responses to control inflammation. Furthermore, we survey recent studies illustrating the role of NOD2 in several inflammatory diseases, in particular, inflammatory bowel disease, of which it is the main susceptibility gene. Keywords: innate immunity, intestinal homeostasis, ER stress, autophagy, inflammatory bowel disease, extraintestinal disease

  14. Can Earth Sciences Help Alleviate Global Poverty?

    Science.gov (United States)

    Mutter, J. C.

    2004-12-01

    essential and could hold the key to making gains toward alleviating the burden of global poverty.

  15. Stages of Small Intestine Cancer

    Science.gov (United States)

    ... all of an organ that contains cancer. The resection may include the small intestine and nearby organs (if the cancer has spread). The doctor may remove the section of the small intestine that contains cancer and perform an anastomosis (joining the cut ends of the intestine together). ...

  16. COPD exacerbations, inflammation and treatment

    NARCIS (Netherlands)

    Bathoorn, Derk

    2007-01-01

    This thesis describes investigations into the inflammation in COPD, and its treatment. Inflammation in COPD is a central factor in the onset of the disease and its progression. During acute deteriorations of the disease, exacerbations, the inflammation is more severe, and depending on the cause of

  17. Aqueous extract of Hibiscus sabdarrifa calyx alleviates anemia and ...

    African Journals Online (AJOL)

    Aqueous extract of Hibiscus sabdarrifa calyx alleviates anemia and organ damage in Trypanosoma brucei brucei infected rats. IA Umar, E Daikwo, NG Maryoms, A Gidado, LB Buratai, FS Saka, MA Ibrahim ...

  18. Intestinal inflammatory myofibroblastic tumour

    African Journals Online (AJOL)

    abdominal X-ray of patients 1, 3 and 4 demonstrated dilated small bowel loops with fluid levels in keeping with intestinal ... myxoid/vascular pattern characterised by a variable admixture of capillary-calibre blood vessels, .... in the present study had a past history of abdominal trauma or surgery. Ancillary histopathological ...

  19. Small intestine and microbiota.

    Science.gov (United States)

    Cotter, Paul D

    2011-03-01

    To highlight the recent studies which have enhanced our appreciation of the composition of the microbiota in the human small intestine and its relevance to the health of the host. In the past number of years, the composition of the microorganisms present in our small intestines has been the subject of greater scrutiny than ever before. These investigations have been possible as a consequence of the development and utilization of new molecular tools which have revolutionized the field of microbial ecology and have focused predominantly on the small intestinal microbiota associated with pediatric celiac disease, inflammatory bowel disease, irritable bowel syndrome and pouchitis. The impact of invasive procedures, such as small bowel transplant, ileostomy and ileal pouch anal anastomosis, on the ileal microbiota has also been investigated. The ever greater appreciation of the link between the small intestinal microbiota and the health status of the host has the potential to lead to the development of new strategies to alter this microbiota in a targeted way to prevent or treat specific disorders.

  20. Intestinal obstruction repair

    Science.gov (United States)

    ... Ileostomy and your diet Ileostomy - caring for your stoma Ileostomy - changing your pouch Ileostomy - discharge Ileostomy - what to ask your doctor Intestinal or bowel obstruction - discharge Low-fiber diet Surgical wound care - open Types of ileostomy When you have nausea ...

  1. adhesive intestinal obstruction

    African Journals Online (AJOL)

    2006-06-01

    Jun 1, 2006 ... obstruction. Brit. I. Surg. 1998; 85: 1071-1074. The acute abdomen: Intestinal obstruction. In: Primary surgery, Vol. 1. Edited by Maurice King et al. Oxford. Med. PubL, Oxford. 1990; 142-169. Fluids and electrolyte management. In: Essentials of pediatric surgery. Edited by Marc Rowe et al. Mosby,. St. Louis ...

  2. Intestinal Complications of IBD

    Science.gov (United States)

    ... localized pocket of pus caused by infection from bacteria. More common in Crohn’s than in colitis, an abscess may form in the intestinal wall—sometimes causing it to bulge out. Visible abscesses, such as those around the anus, look like boils and treatment often involves lancing. Symptoms of ...

  3. Intestinal failure in childhood

    African Journals Online (AJOL)

    Short bowel syndrome (SBS) was one of the first recognised conditions of protracted IF. With the increasing and successful use of long-term PN during the last three decades, several other causes of IF have emerged. Long-term PN and home-PN are the mainstay of therapy, independent of the nature of “Intestinal failure” ...

  4. Entrepreneurship Development and Poverty Alleviation: An Empirical Review

    OpenAIRE

    Mohammad Delwar Hussain; Rosni Bakar; Abul Bashar Bhuiyan

    2014-01-01

    The main purpose of this paper is to corroborate the relationship between entrepreneurship development and poverty alleviation constructed on empirical reviews. In this study, we conducted general search to accumulate empirical literatures by the name of entrepreneurship development and poverty alleviation in different online database sources such as Google Scholars, Springer Link, Wiley, Science Direct, JSTOR, Emerald full text, Scopus, and EBSCO HOST etc. We found innovation, entrepreneursh...

  5. Intestinal fungi contribute to development of alcoholic liver disease

    Science.gov (United States)

    Yang, An-Ming; Inamine, Tatsuo; Hochrath, Katrin; Chen, Peng; Wang, Lirui; Llorente, Cristina; Bluemel, Sena; Hartmann, Phillipp; Koyama, Yukinori; Kisseleva, Tatiana; Torralba, Manolito G.; Moncera, Kelvin; Beeri, Karen; Chen, Chien-Sheng; Freese, Kim; Hellerbrand, Claus; Lee, Serene M.L.; Hoffman, Hal M.; Mehal, Wajahat Z.; Garcia-Tsao, Guadalupe; Mutlu, Ece A.; Keshavarzian, Ali; Brown, Gordon D.; Bataller, Ramon; Stärkel, Peter; Fouts, Derrick E.

    2017-01-01

    Chronic liver disease with cirrhosis is the 12th leading cause of death in the United States, and alcoholic liver disease accounts for approximately half of all cirrhosis deaths. Chronic alcohol consumption is associated with intestinal bacterial dysbiosis, yet we understand little about the contribution of intestinal fungi, or mycobiota, to alcoholic liver disease. Here we have demonstrated that chronic alcohol administration increases mycobiota populations and translocation of fungal β-glucan into systemic circulation in mice. Treating mice with antifungal agents reduced intestinal fungal overgrowth, decreased β-glucan translocation, and ameliorated ethanol-induced liver disease. Using bone marrow chimeric mice, we found that β-glucan induces liver inflammation via the C-type lectin–like receptor CLEC7A on Kupffer cells and possibly other bone marrow–derived cells. Subsequent increases in IL-1β expression and secretion contributed to hepatocyte damage and promoted development of ethanol-induced liver disease. We observed that alcohol-dependent patients displayed reduced intestinal fungal diversity and Candida overgrowth. Compared with healthy individuals and patients with non–alcohol-related cirrhosis, alcoholic cirrhosis patients had increased systemic exposure and immune response to mycobiota. Moreover, the levels of extraintestinal exposure and immune response correlated with mortality. Thus, chronic alcohol consumption is associated with an altered mycobiota and translocation of fungal products. Manipulating the intestinal mycobiome might be an effective strategy for attenuating alcohol-related liver disease. PMID:28530644

  6. Postconditioning attenuates acute intestinal ischemia–reperfusion injury

    Directory of Open Access Journals (Sweden)

    Ilker Sengul

    2013-03-01

    Full Text Available The aim of this study was to test the hypothesis that postconditioning (POC would reduce the detrimental effects of the acute intestinal ischemia–reperfusion (I/R compared to those of the abrupt onset of reperfusion. POC has a protective effect on intestinal I/R injury by inhibiting events in the early minutes of reperfusion in rats. Twenty-four Wistar–Albino rats were subjected to the occlusion of superior mesenteric artery for 30 minutes, then reperfused for 120 minutes, and randomized to the four different modalities of POC: (1 control (no intervention; (2 POC-3 (three cycles of 10 seconds of reperfusion–reocclusion, 1 minute total intervention; (3 POC-6 (six cycles of 10 seconds of reperfusion–reocclusion, 2 minutes total intervention; and (4 sham operation (laparotomy only. The arterial blood samples [0.3 mL total creatine kinase (CK and 0.6 mL malondialdehyde (MDA] and the intestinal mucosal MDA were collected from each after reperfusion. POC, especially POC-6, was effective in attenuating postischemic pathology by decreasing the intestinal tissue MDA levels, serum total CK activity, inflammation, and total histopathological injury scores. POC exerted a protective effect on the intestinal mucosa by reducing the mesenteric oxidant generation, lipid peroxidation, and neutrophil accumulation. The six-cycle algorithm demonstrated the best protection.

  7. Inflammation in Epileptic Encephalopathies.

    Science.gov (United States)

    Shandra, Oleksii; Moshé, Solomon L; Galanopoulou, Aristea S

    2017-01-01

    West syndrome (WS) is an infantile epileptic encephalopathy that manifests with infantile spasms (IS), hypsarrhythmia (in ~60% of infants), and poor neurodevelopmental outcomes. The etiologies of WS can be structural-metabolic pathologies (~60%), genetic (12%-15%), or of unknown origin. The current treatment options include hormonal treatment (adrenocorticotropic hormone and high-dose steroids) and the GABA aminotransferase inhibitor vigabatrin, while ketogenic diet can be given as add-on treatment in refractory IS. There is a need to identify new therapeutic targets and more effective treatments for WS. Theories about the role of inflammatory pathways in the pathogenesis and treatment of WS have emerged, being supported by both clinical and preclinical data from animal models of WS. Ongoing advances in genetics have revealed numerous genes involved in the pathogenesis of WS, including genes directly or indirectly involved in inflammation. Inflammatory pathways also interact with other signaling pathways implicated in WS, such as the neuroendocrine pathway. Furthermore, seizures may also activate proinflammatory pathways raising the possibility that inflammation can be a consequence of seizures and epileptogenic processes. With this targeted review, we plan to discuss the evidence pro and against the following key questions. Does activation of inflammatory pathways in the brain cause epilepsy in WS and does it contribute to the associated comorbidities and progression? Can activation of certain inflammatory pathways be a compensatory or protective event? Are there interactions between inflammation and the neuroendocrine system that contribute to the pathogenesis of WS? Does activation of brain inflammatory signaling pathways contribute to the transition of WS to Lennox-Gastaut syndrome? Are there any lead candidates or unexplored targets for future therapy development for WS targeting inflammation? © 2017 Elsevier Inc. All rights reserved.

  8. Peritoneal dialysis and inflammation.

    Science.gov (United States)

    Velloso, Marina Souza Silva; Otoni, Alba; de Paula Sabino, Adriano; de Castro, Whocely Victor; Pinto, Sérgio Wyton Lima; Marinho, Maria Aparecida Silva; Rios, Danyelle Romana Alves

    2014-03-20

    Peritoneal dialysis (PD) is a kidney replacement therapy for end stage renal disease (ESRD) patients. Despite being a lifesaving treatment, the rate of mortality in patients under PD is elevated, mainly due to the chronic peritoneal dysfunction which is characterized by inflammation, peritoneal fibrosis and neoangiogenesis. The inflammatory process is trigged and modulated by the type of the peritoneal dialysis solutions (PDSs) used during PD. Currently, different PDSs are commercially available: (i) the conventional solutions; (ii) solutions of neutral pH containing low concentration of glucose degradation products (GDPs); (iii) solutions with icodextrin; and (iv) solutions containing taurine. Therefore, the aim of this review is to describe the different types of peritoneal dialysis solutions used during PD and their relationship with systemic and intraperitoneal inflammation. Some studies suggested that solutions of neutral pH containing low concentration of GDPs, icodextrin and taurine have better biocompatibility and lower influence on the inflammatory process compared to the conventional one. On the other hand, the studies, in general, were performed with a small population and for a short period of time. Therefore, further well-designed and -controlled clinical trials with larger number of individuals are required in order to better understand the role of different peritoneal dialysis solution types in the development of inflammation in patients with chronic peritoneal dialysis. Accordingly, studies that are more well-designed, well-controlled and with a larger number of patients are needed to explain and define the role of different types of PDS in the inflammation development in patients with chronic peritoneal dialysis. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Inflammation in epileptic encephalopathies

    Science.gov (United States)

    Shandra, Oleksii; Moshé, Solomon L.; Galanopoulou, Aristea S.

    2017-01-01

    West syndrome (WS) is an infantile epileptic encephalopathy (EE) that manifests with infantile spasms, hypsarrhythmia (in ~60% of infants) and poor neurodevelopmental outcomes. The etiologies of WS can be structural-metabolic pathologies (~60%), genetic (12–15%) or of unknown origin. The current treatment options include hormonal treatment [adrenocorticotropic hormone (ACTH) and high dose steroids], the GABA aminotransferase inhibitor vigabatrin, while ketogenic diet can be given as add-on treatment in refractory IS. There is a need to identify new therapeutic targets and more effective treatments for WS. Theories about the role of inflammatory pathways in the pathogenesis and treatment of WS have emerged, being supported by both clinical and preclinical data from animal models of WS. Ongoing advances in genetics have revealed numerous genes involved in the pathogenesis of WS, including genes directly or indirectly involved in inflammation. Inflammatory pathways also interact with other signaling pathways implicated in WS, such as the neuroendocrine pathway. Furthermore, seizures may also activate pro-inflammatory pathways raising the possibility that inflammation can be a consequence of seizures and epileptogenic processes. With this targeted review we plan to discuss the evidence pro and against the following key questions. Does activation of inflammatory pathways in the brain cause epilepsy in WS and does it contribute to the associated comorbidities and progression? Can activation of certain inflammatory pathways be a compensatory or protective event? Are there interactions between inflammation and the neuroendocrine system that contribute to the pathogenesis of West syndrome? Does activation of brain inflammatory signaling pathways contribute to the transition of WS to Lennox-Gastaut syndrome? Are there any lead candidates or unexplored targets for future therapy development for WS targeting inflammation? PMID:28427564

  10. Crystals, inflammation, and osteoarthritis.

    Science.gov (United States)

    Rosenthal, Ann K

    2011-03-01

    Calcium pyrophosphate dihydrate (CPPD) and basic calcium phosphate (BCP) crystals are common components of osteoarthritic joint fluids and tissues. Why these crystals form and how they contribute to joint damage in osteoarthritis remain unclear. With renewed interest in inflammation as a key component of osteoarthritis the role of calcium-containing crystals in this common disease warrants re-examination. There is ample evidence supporting a pathogenic role for inflammation in osteoarthritis, and the innate immune system likely participates in this inflammatory process. Recent work reinforces the almost universal existence of calcium-containing crystals in tissues from patients with end-stage osteoarthritis. Calcium-containing crystals may contribute to inflammation in osteoarthritis tissues through their direct interactions with components of the innate immune system, as well as by inducing or amplifying other inflammatory signals. There is increasing evidence that calcium-containing crystals contribute to osteoarthritis and their inflammatory properties may mediate detrimental effects through innate immunity signals. Calcium-containing crystals may thus represent important therapeutic targets in osteoarthritis.

  11. Modification of composition and spatial distribution of intestinal microbiota following antibiotic therapy in immunocompetent defined flora C3H/HeN mice

    Science.gov (United States)

    Background: Luminal bacteria and/or their products play a pivotal role in the pathogenesis of chronic intestinal inflammation associated with inflammatory bowel diseases (IBD). While host responses to resident flora may initiate IBD, the subsets of bacteria responsible for mediating inflammation in ...

  12. Intraluminal Flagellin Differentially Contributes to Gut Dysbiosis and Systemic Inflammation following Burn Injury.

    Directory of Open Access Journals (Sweden)

    Logan Grimes

    Full Text Available Burn injury is associated with a loss of gut barrier function, resulting in systemic dissemination of gut-derived bacteria and their products. The bacterial protein and TLR5 agonist, flagellin, induces non-specific innate immune responses. Because we detected flagellin in the serum of burn patients, we investigated whether gut-derived flagellin was a primary or secondary contributor to intestinal dysfunction and systemic inflammation following burn injury. The apical surface of polarized human intestinal epithelial cells (IECs, Caco-2BBe, were exposed to 50 or 500 ng of purified flagellin and 1 x 105 of an intestinal E. coli (EC isolate as follows: 1 flagellin added 30 min prior to EC, 2 flagellin and EC added simultaneously, or 3 EC added 30 min prior to flagellin. Our results showed that luminal flagellin and EC modulated each other's biological actions, which influenced their ability to induce basolateral secretion of inflammatory cytokines and subsequent translocation of bacteria and their products. A low dose of flagellin accompanied by an enteric EC in the lumen, tempered inflammation in a dose- and time-dependent manner. However, higher doses of flagellin acted synergistically with EC to induce both intestinal and systemic inflammation that compromised barrier integrity, increasing systemic inflammation following burn injury, a process we have termed flagellemia. In a murine model of burn injury we found that oral gavage of flagellin (1 μg/mouse significantly affected the gut microbiome after burn injury. In these mice, flagellin disseminated out of the intestine into the serum and to distal organs (mesenteric lymph nodes and lungs where it induced secretion of monocyte chemoattractant protein (MCP-1 and CXCL1/KC (mouse equivalent of human IL-8 at 24 and 48h post-burn. Our results illustrated that gut-derived flagellin alone or accompanied by a non-pathogenic enteric EC strain can function as an initiator of luminal and systemic

  13. Preclinical Cancer Chemoprevention Studies Using Animal Model of Inflammation-Associated Colorectal Carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, Takuji [Cytopatholgy Division, Tohkai Cytopathology Institute, Cancer Research and Prevention (TCI-CaRP), 5-1-2 Minami-uzura, Gifu 500-8285 (Japan); Department of Tumor Pathology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194 (Japan)

    2012-07-16

    Inflammation is involved in all stages of carcinogenesis. Inflammatory bowel disease, such as ulcerative colitis and Crohn’s disease is a longstanding inflammatory disease of intestine with increased risk for colorectal cancer (CRC). Several molecular events involved in chronic inflammatory process are reported to contribute to multi-step carcinogenesis of CRC in the inflamed colon. They include over-production of free radicals, reactive oxygen and nitrogen species, up-regulation of inflammatory enzymes in arachidonic acid biosynthesis pathway, up-regulation of certain cytokines, and intestinal immune system dysfunction. In this article, firstly I briefly introduce our experimental animal models where colorectal neoplasms rapidly develop in the inflamed colorectum. Secondary, data on preclinical cancer chemoprevention studies of inflammation-associated colon carcinogenesis by morin, bezafibrate, and valproic acid, using this novel inflammation-related colorectal carcinogenesis model is described.

  14. Preclinical Cancer Chemoprevention Studies Using Animal Model of Inflammation-Associated Colorectal Carcinogenesis

    International Nuclear Information System (INIS)

    Tanaka, Takuji

    2012-01-01

    Inflammation is involved in all stages of carcinogenesis. Inflammatory bowel disease, such as ulcerative colitis and Crohn’s disease is a longstanding inflammatory disease of intestine with increased risk for colorectal cancer (CRC). Several molecular events involved in chronic inflammatory process are reported to contribute to multi-step carcinogenesis of CRC in the inflamed colon. They include over-production of free radicals, reactive oxygen and nitrogen species, up-regulation of inflammatory enzymes in arachidonic acid biosynthesis pathway, up-regulation of certain cytokines, and intestinal immune system dysfunction. In this article, firstly I briefly introduce our experimental animal models where colorectal neoplasms rapidly develop in the inflamed colorectum. Secondary, data on preclinical cancer chemoprevention studies of inflammation-associated colon carcinogenesis by morin, bezafibrate, and valproic acid, using this novel inflammation-related colorectal carcinogenesis model is described

  15. Comparative study of cotton, polyglactin and polyglecaprone sutures in intestinal anastomoses in dogs.

    Science.gov (United States)

    Bernis-Filho, Walter Octaviano; Wouters, Flademir; Wouters, Angélica Aparecida Barth; Bernis, Valéria Magro Octaviano; Lopes, Luiz Roberto; Andreollo, Nelson Adami

    2013-01-01

    Over the years, many sutures were developed and then abandoned. Until now was not found an ideal suture to the intestinal tract or other tissues in general, making the choice a difficult task. To evaluate, macroscopically and microscopically, the healing process of intestinal anastomoses in dogs using polyglecaprone 25, polyglactin 910 and cotton sutures. Twenty adult male dogs were operated on and underwent to three small bowel anastomosis using the technique with submucosal sutures. Were used three threads and the anastomoses were evaluated at different postoperative periods - group I - three days; group II - seven days; group III - 14 days and group IV - 21days. Macroscopic analysis was to assess the presence or absence of peritonitis, aspect of the anastomosis and adhesions. Histological studies of the anastomoses, using hematoxylin and eosin and Masson's trichrome analyzed the exudative inflammation, granulomatous inflammation, the mucosal epithelial coating and collagen fibers. The macroscopic analysis showed good coaptation of the edges with a moderate degree of adhesion between the intestines and omentum three to 21 days after surgery. The microscopic evaluation revealed exudative inflammation with neutrophils and fibrin, which ranged from mild to moderate until the 14th day; granulomatous inflammation with macrophages, multinucleated giant cells and epithelioid cells were more evident at 14th day for the cotton, presence of granulation tissue (fibroblasts) and collagen fibers, a moderate way, from the 7th for the three threads. All three threads showed similar behavior and thus they can be indicated for anastomoses of the small intestine.

  16. Interactions between intestinal microbiota and innate immune system in pediatric inflammatory bowel disease.

    Science.gov (United States)

    Cucchiara, Salvatore; Stronati, Laura; Aloi, Marina

    2012-10-01

    Inflammatory bowel disease (IBD) is the result of an altered immune homeostasis within the intestinal mucosa against the gut microbiota, leading to chronic inflammation in genetically predisposed individuals. Under normal conditions, the immune system defends against pathogens and prevents the passage of excessive intestinal bacteria; regulatory pathways must maintain a low-grade, controlled inflammation in a healthy gut, but also induce a protective response against pathogens. The innate immune system is the first-line defense from microbes; dendritic cells, macrophages, and epithelial cells produce an initial, immediate response. The immune system constantly controls commensal bacteria and utilizes constitutive antimicrobial mechanisms to sustain immune homeostasis. The discovery that several genes linked to IBD modulate microbial recognition and innate immune pathways, such as nucleotide oligomerization domain 2 (Nod2), and genes that mediate autophagy (ie, ATG16L1, IRGM), has highlighted the critical role of host-microbe interactions in controlling intestinal immune homeostasis. Commensal microorganisms actively interact with the intestinal mucosa and influence the activity of the immune system as well as the amplitude of the immune response. In contrast, host factors can influence microbes, which in turn modulate disease susceptibility. In this paper, we focus on the mechanisms that mediate host-microbe interactions and how the disruption of this balance leads to chronic intestinal inflammation in IBD.

  17. Maintaining Intestinal Health: The Genetics and Immunology of Very Early Onset Inflammatory Bowel DiseaseSummary

    Directory of Open Access Journals (Sweden)

    Judith R. Kelsen

    2015-09-01

    Full Text Available Inflammatory bowel disease (IBD is a multifactoral disease caused by dysregulated immune responses to commensal or pathogenic microbes in the intestine, resulting in chronic intestinal inflammation. An emerging population of patients with IBD younger than 5 years of age represent a unique form of disease, termed very early onset IBD (VEO-IBD, which is phenotypically and genetically distinct from older-onset IBD. VEO-IBD is associated with increased disease severity, aggressive progression, and poor responsiveness to most conventional therapies. Further investigation into the causes and pathogenesis of VEO-IBD will help improve treatment strategies and may lead to a better understanding of the mechanisms that are essential to maintain intestinal health or provoke the development of targeted therapeutic strategies to limit intestinal inflammation and promote tissue repair. Here, we discuss the phenotypic nature of VEO-IBD, the recent identification of novel gene variants associated with disease, and functional immunologic studies interrogating the contribution of specific genetic variants to the development of chronic intestinal inflammation. Keywords: Inflammatory Bowel Disease, Very Early Onset Inflammatory Bowel Disease, Whole Exome Sequencing, Mucosal Immunology

  18. Intestinal barrier function and the brain-gut axis.

    Science.gov (United States)

    Alonso, Carmen; Vicario, María; Pigrau, Marc; Lobo, Beatriz; Santos, Javier

    2014-01-01

    The luminal-mucosal interface of the intestinal tract is the first relevant location where microorganism-derived antigens and all other potentially immunogenic particles face the scrutiny of the powerful mammalian immune system. Upon regular functioning conditions, the intestinal barrier is able to effectively prevent most environmental and external antigens to interact openly with the numerous and versatile elements that compose the mucosal-associated immune system. This evolutionary super system is capable of processing an astonishing amount of antigens and non-immunogenic particles, approximately 100 tons in one individual lifetime, only considering food-derived components. Most important, to develop oral tolerance and proper active immune responses needed to prevent disease and inflammation, this giant immunogenic load has to be managed in a way that physiological inflammatory balance is constantly preserved. Adequate functioning of the intestinal barrier involves local and distant regulatory networks integrating the so-called brain-gut axis. Along this complex axis both brain and gut structures participate in the processing and execution of response signals to external and internal changes coming from the digestive tract, using multidirectional pathways to communicate. Dysfunction of brain-gut axis facilitates malfunctioning of the intestinal barrier, and vice versa, increasing the risk of uncontrolled immunological reactions that may trigger mucosal and brain low-grade inflammation, a putative first step to the initiation of more permanent gut disorders. In this chapter, we describe the structure, function and interactions of intestinal barrier, microbiota and brain-gut axis in both healthy and pathological conditions.

  19. Melatonin alleviates inflammasome-induced pyroptosis through inhibiting NF-κB/GSDMD signal in mice adipose tissue.

    Science.gov (United States)

    Liu, Zhenjiang; Gan, Lu; Xu, Yatao; Luo, Dan; Ren, Qian; Wu, Song; Sun, Chao

    2017-08-01

    Pyroptosis is a proinflammatory form of cell death that is associated with pathogenesis of many chronic inflammatory diseases. Melatonin is substantially reported to possess anti-inflammatory properties by inhibiting inflammasome activation. However, the effects of melatonin on inflammasome-induced pyroptosis in adipocytes remain elusive. Here, we demonstrated that melatonin alleviated lipopolysaccharides (LPS)-induced inflammation and NLRP3 inflammasome formation in mice adipose tissue. The NLRP3 inflammasome-mediated pyroptosis was also inhibited by melatonin in adipocytes. Further analysis revealed that gasdermin D (GSDMD), the key executioner of pyroptosis, was the target for melatonin inhibition of adipocyte pyroptosis. Importantly, we determined that nuclear factor κB (NF-κB) signal was required for the GSDMD-mediated pyroptosis in adipocytes. We also confirmed that melatonin alleviated adipocyte pyroptosis by transcriptional suppression of GSDMD. Moreover, GSDMD physically interacted with interferon regulatory factor 7 (IRF7) and subsequently formed a complex to promote adipocyte pyroptosis. Melatonin also attenuated NLRP3 inflammasome activation and pyroptosis, which was induced by LPS or obesity. In summary, our results demonstrate that melatonin alleviates inflammasome-induced pyroptosis by blocking NF-κB/GSDMD signal in mice adipose tissue. Our data reveal a novel function of melatonin on adipocyte pyroptosis, suggesting a new potential therapy for melatonin to prevent and treat obesity caused systemic inflammatory response. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Dopamine D2 Receptor Is Involved in Alleviation of Type II Collagen-Induced Arthritis in Mice.

    Science.gov (United States)

    Lu, Jian-Hua; Liu, Yi-Qian; Deng, Qiao-Wen; Peng, Yu-Ping; Qiu, Yi-Hua

    2015-01-01

    Human and murine lymphocytes express dopamine (DA) D2-like receptors including DRD2, DRD3, and DRD4. However, their roles in rheumatoid arthritis (RA) are less clear. Here we showed that lymphocyte DRD2 activation alleviates both imbalance of T-helper (Th)17/T-regulatory (Treg) cells and inflamed symptoms in a mouse arthritis model of RA. Collagen-induced arthritis (CIA) was prepared by intradermal injection of chicken collagen type II (CII) in tail base of DBA/1 mice or Drd2 (-/-) C57BL/6 mice. D2-like receptor agonist quinpirole downregulated expression of proinflammatory Th17-related cytokines interleukin- (IL-) 17 and IL-22 but further upregulated expression of anti-inflammatory Treg-related cytokines transforming growth fa