44 research outputs found

    Effect of the CLA and VSL#3 treatment on colon histopathology on experimental <i>Helicobacter typhlonius</i>-induced colorectal cancer.

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    <p>Bacterial-free 129/SvEv and IL-10 gene deficient (IL-10−/−) 129/SvEv mice in a 129/SvEv background (n = 60) were treated with the VSL#3 probiotic (n = 20), CLA-supplemented (1 g/100 g) (n = 20) or control diets (n = 20) for 32 days and then were infected with <i>H. typhlonius</i> in order to develop experimental colorectal cancer associated with colitis. After the necropsy, all specimens underwent blinded histological examination and were scored 1–4 on mucosal wall thickening (A), leukocyte infiltration (B), adenomas (C) and adenocarcinomas (D). Data are represented as mean ± standard error. Points with an asterisk are significantly different when compared to the control group (<i>P</i><0.05).</p

    Effect of VSL#3 and dietary conjugated linoleic acid (CLA) supplementation on experimental <i>Helicobacter typhlonius</i>-induced colorectal cancer.

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    <p>Bacterial-free 129/SvEv and IL-10 gene deficient (IL-10−/−) 129/SvEv mice in a 129/SvEv background (n = 60) were treated with the VSL#3 probiotic (n = 20), CLA-supplemented (1 g/100 g) (n = 20) or control diets (n = 20) for 32 days and then were infected with <i>H. typhlonius</i> in order to develop experimental colorectal cancer associated with colitis. The disease activity index, a composite score reflecting clinical signs of the disease, was assessed daily for mice undergoing the DSS challenge (A). Colon, spleen and mesenteric lymph nodes (MLN) (B–D) were macroscopically scored for inflammation. Data are represented as mean ± standard error. Points with an asterisk are significantly different when compared to the control group (<i>P</i><0.05).</p

    VSL#3 and conjugated linoleic acid (CLA) modulate colonic gene expression.

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    <p>C57BL/6J mice (n = 60) were treated with the VSL#3 probiotic (n = 20), CLA-supplemented (1 g/100 g) (n = 20) or control diets (n = 20) for 32 days and challenged i.p. with azoxymethane (10 mg/kg) followed by 2% dextran sodium sulfate (DSS) in the drinking water for 7 days to induce colitis-associated colorectal cancer (CRC). Mice were euthanized on day 68. Expression of CD36 (A), cyclooxygenase 2 (COX2) (B), peroxisome proliferator-activated receptor γ (PPAR γ) (C) and angiostatin (D) were assessed by real-time quantitative PCR. Data are represented as mean ± standard error. Points with an asterisk are significantly different when compared to the control group (<i>P</i><0.05).</p

    Effect of VSL#3 and dietary conjugated linoleic acid (CLA) supplementation on experimental azoxymethane-induced colorectal cancer.

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    <p>C57BL/6J mice (n = 60) were treated with the VSL#3 probiotic (n = 20), CLA-supplemented (1 g/100 g) (n = 20) or control diets (n = 20) for 32 days and challenged i.p. with azoxymethane (10 mg/kg) followed by 2% dextran sodium sulfate (DSS) in the drinking water for 7 days to induce colitis-associated colorectal cancer (CRC). The disease activity index, a composite score reflecting clinical signs of the disease (i.e. perianal soiling, rectal bleeding, diarrhea, and piloerection) was assessed daily for mice undergoing the DSS challenge (A). Mice were euthanized on day 68. Colon and mesenteric lymph nodes (MLN) (B&C) were macroscopically scored for inflammation. Data are represented as mean ± standard error. Points with an asterisk are significantly different when compared to the control group (<i>P</i><0.05).</p

    VSL#3 and conjugated linoleic acid (CLA) modulate immune cell subsets in mesenteric lymph nodes (MLN), colonic lamina propria lymphocytes (LPL) and spleen.

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    <p>C57BL/6J mice (n = 60) were treated with the VSL#3 probiotic (n = 20), CLA-supplemented (1 g/100 g) (n = 20) or control diets (n = 20) for 32 days and challenged i.p. with azoxymethane (10 mg/kg) followed by 2% dextran sodium sulfate (DSS) in the drinking water for 7 days to induce colitis-associated colorectal cancer (CRC). Mice were euthanized on day 68. MLN (A–C), spleen (D) and LPL (E–F) from wild type mice were immunophenotyped to identify immune cells subsets by flow cytometry. Data are represented as mean ± standard error. Points with an asterisk are significantly different when compared to the control group (<i>P</i><0.05).</p

    The Role of Peroxisome Proliferator-Activated Receptor γ in Immune Responses to Enteroaggregative <em>Escherichia coli</em> Infection

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    <div><p>Background</p><p>Enteroaggregative <i>Escherichia coli</i> (EAEC) is recognized as an emerging cause of persistent diarrhea and enteric disease worldwide. Mucosal immunity towards EAEC infections is incompletely understood due in part to the lack of appropriate animal models. This study presents a new mouse model and investigates the role of peroxisome proliferator-activated receptor gamma (PPARγ) in the modulation of host responses to EAEC in nourished and malnourished mice.</p> <p>Methods/Principal Findings</p><p>Wild-type and T cell-specific PPARγ null C57BL/6 mice were fed protein-deficient diets at weaning and challenged with 5×10<sup>9</sup>cfu EAEC strain JM221 to measure colonic gene expression and immune responses to EAEC. Antigen-specific responses to <i>E. coli</i> antigens were measured in nourished and malnourished mice following infection and demonstrated the immunosuppressive effects of malnutrition at the cellular level. At the molecular level, both pharmacological blockade and deletion of PPARγ in T cells resulted in upregulation of TGF-β, IL-6, IL-17 and anti-microbial peptides, enhanced Th17 responses, fewer colonic lesions, faster clearance of EAEC, and improved recovery. The beneficial effects of PPARγ blockade on weight loss and EAEC clearance were abrogated by neutralizing IL-17 <i>in vivo</i>.</p> <p>Conclusions</p><p>Our studies provide <i>in vivo</i> evidence supporting the beneficial role of mucosal innate and effector T cell responses on EAEC burden and suggest pharmacological blockade of PPARγ as a novel therapeutic intervention for EAEC infection.</p> </div

    Pharmacological blockade of peroxisome proliferator-activated receptor γ (PPARγ) associated with antimicrobial response and bacterial clearance.

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    <p>Enteroaggregative <i>Escherichia coli</i> (EAEC) burden in colon was assessed by quantitative real time RT-PCR using bacterial DNA isolated from feces of infected mice treated with PPARγ antagonist GW9662 (n = 9) or left untreated (n = 9). Data is presented as CFU/mg of tissue. S100A8 and S100A9 gene expression was analyzed in colonic tissue from C57BL/6 malnourished mice at day 5 days PI (n = 10) using quantitative real-time RT-PCR (B and C). S100 proteins are presented as values normalized to β-actin. Asterisks indicate values where differences are statistically significant (<i>p</i><0.05).</p

    Immune responses during enteroaggregative Escherichia coli (EAEC) infection in peroxisome proliferator-activated receptor γ (PPARγ)-deficient mice associated with bacterial clearance.

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    <p>Antigen specific recall responses of spleenocytes from mice infected with EAEC were measured ex vivo using the lymphocyte blastogenesis test. EAEC JM221 whole cell and whole cell sonicate were used in parallel to two negative controls, <i>E. coli</i> HS and mutant EAEC Aff/I strains as well as one positive control, concanavalin A (ConA). Lymphocyte proliferation is expressed stimulation indexes which are calculated by dividing the counts per minute (CPM) of antigen-stimulated wells by the CPM of unstimulated wells (A). IL-17 expression was assessed in colonic lamina propria (B) and whole blood (C) CD4+ T cells by flow cytometry and in the colon by quantitative real time RT-PCR (D) 14 days PI. Mice per group: n = 10. Asterisks indicate values where differences are statistically significant (<i>p</i><0.05) while bars connect groups where comparisons are made.</p

    Gene expression suggests a T helper 17 response in mice when peroxisome proliferator-activated receptor γ (PPARγ) is antagonized.

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    <p>Gene expression data from colonic tissue of malnourished C57BL/6 mice was analyzed using quantitative real-time RT-PCR and reported as values normalized to β-actin. IL-6, IL-1β, MCP-1, CCL20, and CXCL1 were quantified at day 5PI (mice per group: n = 10) (A–E) while IL-6, TGF-β, and IL-17 were quantified 14 days PI (n = 10) (F–H). Asterisks indicate values where differences are statistically significant (<i>p</i><0.05) while bars connect groups where comparisons are made.</p

    Early beneficial effects of PPARγ deficiency in T cells during enteroaggregative Escherichia coli (EAEC) challenge.

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    <p>Growth retardation in wild type (A) and T cell specific PPARγ deficient mice (B) is expressed as percent growth from day 0 after challenge. Gene expression for IL-6 and TNF-α in colonic tissue of malnourished C57BL/6 and PPARγ CD4cre+ mice was analyzed using quantitative real-time RT-PCR on day 5 PI (C). Representative photomicrographs of colonic specimens of infected mice at 5 or 14 days PI in infected wild type mice (D,E,I,J), infected mice lacking PPARγ expression in T cells (F,G,K,L), and uninfected controls (H,M). The top panel corresponds to nourished mice whereas the bottom panel corresponds to malnourished mice. Original magnification 200×. Boxes and arrows are areas where an amplified image (400×) is provided to emphasize examples of leukocyte infiltration, mucosal thickening, goblet cell hyperplasia, and vasodilation. Mice per group: n = 8. Asterisks indicate values where differences are statistically significant (<i>p</i><0.05).</p
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