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Escherichia coli Nissle 1917 distinctively modulates T-cell cycling and expansion via toll-like receptor 2 signaling 总被引:2,自引:0,他引:2
Sturm A Rilling K Baumgart DC Gargas K Abou-Ghazalé T Raupach B Eckert J Schumann RR Enders C Sonnenborn U Wiedenmann B Dignass AU 《Infection and immunity》2005,73(3):1452-1465
Although the probiotic Escherichia coli strain Nissle 1917 has been proven to be efficacious for the treatment of inflammatory bowel diseases, the underlying mechanisms of action still remain elusive. The aim of the present study was to analyze the effects of E. coli Nissle 1917 on cell cycling and apoptosis of peripheral blood and lamina propria T cells (PBT and LPT, respectively). Anti-CD3-stimulated PBT and LPT were treated with E. coli Nissle 1917-conditioned medium (E. coli Nissle 1917-CM) or heat-inactivated E. coli Nissle 1917. Cyclin B1, DNA content, and caspase 3 expression were measured by flow cytometry to assess cell cycle kinetics and apoptosis. Protein levels of several cell cycle and apoptosis modulators were determined by immunoblotting, and cytokine profiles were determined by cytometric bead array. E. coli Nissle 1917-CM inhibits cell cycling and expansion of peripheral blood but not mucosal T cells. Bacterial lipoproteins mimicked the effect of E. coli Nissle 1917-CM; in contrast, heat-inactivated E. coli Nissle 1917, lipopolysaccharide, or CpG DNA did not alter PBT cell cycling. E. coli Nissle 1917-CM decreased cyclin D2, B1, and retinoblastoma protein expression, contributing to the reduction of T-cell proliferation. E. coli Nissle 1917 significantly inhibited the expression of interleukin-2 (IL-2), tumor necrosis factor alpha, and gamma interferon but increased IL-10 production in PBT. Using Toll-like receptor 2 (TLR-2) knockout mice, we further demonstrate that the inhibition of PBT proliferation by E. coli Nissle 1917-CM is TLR-2 dependent. The differential reaction of circulating and tissue-bound T cells towards E. coli Nissle 1917 may explain the beneficial effect of E. coli Nissle 1917 in intestinal inflammation. E. coli Nissle 1917 may downregulate the expansion of newly recruited T cells into the mucosa and limit intestinal inflammation, while already activated tissue-bound T cells may eliminate deleterious antigens in order to maintain immunological homeostasis. 相似文献
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Glycol ethers such as ethylene glycol monomethyl ether (EGME)are common solvents used in many industrial products. A largenumber of individuals are exposed to EGME through differentexposure routes. We investigated the differential distributionof EGME following various routes of administration using wholebody autoradiographic (WBA) techniques. Male B6C3F1 mice weretreated with tracer iv or oral doses of [2-14C]EGME.(4.05 µgEGME/kg equivalent to 0.8 mCi/kg) and euthanized at 1 and 24hr following treatment. In both groups of animals the highestlevels of radioactivity were detected in the liver, urinarybladder, bone marrow, kidney, and epididymis, at 1- and 24-hrtime periods. Computer-assisted quantitation of WBA indicatedthat there was markedly higher deposition of [2-14 and/or itsmetabolites in various tissues of the orally treated animalsthan in animals treated intravenously. Our studies also suggestthat [2-14C]EGME is rapidly distributed either from blood orstomach to various tissues. Preferential deposition of radioactivityin the peripheral tissues of the bone, with a progressive inwardaccumulation in the bone marrow, was observed. Selective permeabilityof EGME and/or its metabolites was indicated by the higher uptakeby the epididymis than that by testis. The high levels of radioactivityin biosynthetically active tissues, e.g., the liver, bone marrow,and gastric mucosa, is an indication of persistent interactionof the compound with cellular components of these tissues. Theseinteractions may lead to EGME toxicity. 相似文献
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Zeeh JM Zorlu Riley NE Hoffmann P Ruwe M Goebell H Gerken G Dignass AU 《Scandinavian journal of gastroenterology》2001,36(1):66-70
BACKGROUND: Lymphocytes are widely believed to be responsible for persistent intestinal inflammation in inflammatory bowel diseases. Mycophenolate mofetil (MMF) is a potent immunosuppressant that inhibits lymphocyte proliferation and has been shown to be effective in preventing allograft rejection after organ transplantation. The purpose of this study was to assess the modulating effects of MMF on intestinal inflammation in an experimental model of colitis in rats. METHODS: Colitis was induced by rectal instillation of trinitrobenzenesulfonic acid (TNBS) in ethanol in male Sprague-Dawley rats. One group of rats (n = 10) was treated with MMF i.p. (25 mg/kg b.w.) daily for 1 week starting 24 h after induction of colitis. A second group of rats (n = 10) was treated with MMF at the same dose 2 days, I day and 1 h prior to induction of colitis. Control animals (n = 10) received vehicle only. After being killed, colonic tissue was macroscopically evaluated for necrosis and microscopically for ulcerations. Sections were stained and examined for the presence of granulocytes. RESULTS: Administration of MMF after induction of TNBS colitis reduced macroscopic injury by 62% compared to control animals (P = 0.01). Microscopic ulcerations were reduced by 64% compared to controls (P = 0.009). In addition, posttreatment significantly reduced the number of granulocytes. MMF pretreatment did not significantly prevent macroscopic or microscopic tissue damage, or change the number of granulocytes. CONCLUSION: Systemic administration of MMF significantly ameliorates tissue damage in a model of experimental colitis in rats suggesting that this compound may play an important role as an immunosuppressant in the therapy of inflammatory bowel diseases. 相似文献
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Pascu M Müller AR Wiedenmann B Dignass AU 《International journal of colorectal disease》2003,18(3):271-275
BACKGROUND: Toxic megacolon is a life-threatening complication most commonly observed in patients with ulcerative colitis or Crohn's disease that is characterized by total or segmental nonobstructive colonic dilatation of at least 6 cm on plain abdominal films associated with systemic toxicity. CASE REPORT: We report an unusual case of fulminant steroid-refractory ulcerative colitis complicated by toxic megacolon treated successfully with the immunosuppressant tacrolimus. CONCLUSION: Tacrolimus administration induced clinical remission and bridged the time interval, until the standard immunosuppressant azathioprine could maintain clinical remission, thereby avoiding eminent emergency colectomy. 相似文献
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Blumenstein I Bock H Weber C Rambow A Tacke W Kihn R Pfaff R Orlemann S Schaeffer R Schröder O Dignass A Hartmann F Stein J 《Inflammatory bowel diseases》2008,14(1):53-60
BACKGROUND: Studies examining the treatment reality of IBD patients in Germany have been limited, as networking among deliverers of care and reliable documentation of medical, demographic, and economic data are lacking. The aim of the present study was to establish an internet-based treatment registry in order to evaluate treatment of IBD patients in Germany. METHODS: Between November 1(st), 2005, and January 31, 2007, 1024 outpatients with prevalent IBD from 10 gastroenterological private practices and 3 hospitals (UC = 439, CD = 567, ID = 18) were enrolled in the study. An internet-based registry was established that included data about medical history, disease status, diagnostic procedures, laboratory test results, and medical treatment. Data for private practices and hospitals were pooled in order to compare treatment habits between these types of medical facilities. The cost of medication was determined according to medications prescribed. RESULTS: There was no significant difference between the 2 patient groups in demographic and clinical characteristics. Marked differences were observed in medical treatment. The most frequently prescribed medications in the private practices for patients in remission and those with active disease were aminosalicylates and corticosteroids. Immunomodulators played a marginal role. In contrast, in the hospitals azathioprine/6-MP was predominantly used for the maintenance of remission. Patients with fistulizing CD were treated with infliximab. The mean annual cost of medications was 1826 +/- 1331euro/patient (median 1353euro) in the private practices and 1849euro +/- 2897euro/patient (median 960euro) at the University Hospital. CONCLUSIONS: The registry provides the first detailed data about the reality of treatment of IBD patients in Germany and reveals the necessity for networking among attending physicians in order to implement guidelines-conformed treatment. 相似文献
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