RG Mucosal Immunity (MI)
AG Mukosale Immunitaet (MI)
http://hdl.handle.net/10033/6804
2024-03-28T16:13:31Z
2024-03-28T16:13:31Z
Drug-inducible remote control of gene expression by probiotic Escherichia coli Nissle 1917 in intestine, tumor and gall bladder of mice.
Loessner, Holger
Leschner, Sara
Endmann, Anne
Westphal, Kathrin
Wolf, Kathrin
Kochruebe, Katja
Miloud, Tewfik
Altenbuchner, Josef
Weiss, Siegfried
http://hdl.handle.net/10033/96597
2019-08-30T11:34:48Z
2009-12-01T00:00:00Z
Drug-inducible remote control of gene expression by probiotic Escherichia coli Nissle 1917 in intestine, tumor and gall bladder of mice.
Loessner, Holger; Leschner, Sara; Endmann, Anne; Westphal, Kathrin; Wolf, Kathrin; Kochruebe, Katja; Miloud, Tewfik; Altenbuchner, Josef; Weiss, Siegfried
The probiotic bacterium Escherichia coli Nissle 1917 (EcN) constitutes a prospective vector for delivering heterologous therapeutic molecules to treat several human disorders. To add versatility to this carrier system, bacteria should be equipped with expression modules that can be regulated deliberately in a temporal and quantitative manner. This approach is called in vivo remote control (IVRC) of bacterial vectors. Here, we have evaluated promoters P(araBAD), P(rhaBAD) and P(tet), which can be induced with L-arabinose, L-rhamnose or anhydrotetracycline, respectively. EcN harboring promoter constructs with luciferase as reporter gene were administered either orally to healthy mice or intravenously to tumor bearing animals. Subsequent to bacterial colonization of tissues, inducer substances were administered via the oral or systemic route. By use of in vivo bioluminescence imaging, the time course of reporter gene expression was analyzed. Each promoter displayed a specific in vivo induction profile depending on the niche of bacterial residence and the route of inducer administration. Importantly, we also observed colonization of gall bladders of mice when EcN was administered systemically at high doses. Bacteria in this anatomical compartment remained accessible to remote control of bacterial gene expression.
2009-12-01T00:00:00Z
The host response to the probiotic Escherichia coli strain Nissle 1917: specific up-regulation of the proinflammatory chemokine MCP-1.
Ukena, Sya N
Westendorf, Astrid M
Hansen, Wiebke
Rohde, Manfred
Geffers, Robert
Coldewey, Sina
Suerbaum, Sebastian
Buer, Jan
Gunzer, Florian
http://hdl.handle.net/10033/95975
2019-08-30T11:29:17Z
2005-01-01T00:00:00Z
The host response to the probiotic Escherichia coli strain Nissle 1917: specific up-regulation of the proinflammatory chemokine MCP-1.
Ukena, Sya N; Westendorf, Astrid M; Hansen, Wiebke; Rohde, Manfred; Geffers, Robert; Coldewey, Sina; Suerbaum, Sebastian; Buer, Jan; Gunzer, Florian
BACKGROUND: The use of live microorganisms to influence positively the course of intestinal disorders such as infectious diarrhea or chronic inflammatory conditions has recently gained increasing interest as a therapeutic alternative. In vitro and in vivo investigations have demonstrated that probiotic-host eukaryotic cell interactions evoke a large number of responses potentially responsible for the effects of probiotics. The aim of this study was to improve our understanding of the E. coli Nissle 1917-host interaction by analyzing the gene expression pattern initiated by this probiotic in human intestinal epithelial cells. METHODS: Gene expression profiles of Caco-2 cells treated with E. coli Nissle 1917 were analyzed with microarrays. A second human intestinal cell line and also pieces of small intestine from BALB/c mice were used to confirm regulatory data of selected genes by real-time RT-PCR and cytometric bead array (CBA) to detect secretion of corresponding proteins. RESULTS: Whole genome expression analysis revealed 126 genes specifically regulated after treatment of confluent Caco-2 cells with E. coli Nissle 1917. Among others, expression of genes encoding the proinflammatory molecules monocyte chemoattractant protein-1 ligand 2 (MCP-1), macrophage inflammatory protein-2 alpha (MIP-2alpha) and macrophage inflammatory protein-2 beta (MIP-2beta) was increased up to 10 fold. Caco-2 cells cocultured with E. coli Nissle 1917 also secreted high amounts of MCP-1 protein. Elevated levels of MCP-1 and MIP-2alpha mRNA could be confirmed with Lovo cells. MCP-1 gene expression was also up-regulated in mouse intestinal tissue. CONCLUSION: Thus, probiotic E. coli Nissle 1917 specifically upregulates expression of proinflammatory genes and proteins in human and mouse intestinal epithelial cells.
2005-01-01T00:00:00Z
Probiotic Escherichia coli Nissle 1917 inhibits leaky gut by enhancing mucosal integrity.
Ukena, Sya N
Singh, Anurag
Dringenberg, Ulrike
Engelhardt, Regina
Seidler, Ursula
Hansen, Wiebke
Bleich, André
Bruder, Dunja
Franzke, Anke
Rogler, Gerhard
Suerbaum, Sebastian
Buer, Jan
Gunzer, Florian
Westendorf, Astrid M
http://hdl.handle.net/10033/94153
2019-08-30T11:35:13Z
2007-01-01T00:00:00Z
Probiotic Escherichia coli Nissle 1917 inhibits leaky gut by enhancing mucosal integrity.
Ukena, Sya N; Singh, Anurag; Dringenberg, Ulrike; Engelhardt, Regina; Seidler, Ursula; Hansen, Wiebke; Bleich, André; Bruder, Dunja; Franzke, Anke; Rogler, Gerhard; Suerbaum, Sebastian; Buer, Jan; Gunzer, Florian; Westendorf, Astrid M
BACKGROUND: Probiotics are proposed to positively modulate the intestinal epithelial barrier formed by intestinal epithelial cells (IECs) and intercellular junctions. Disruption of this border alters paracellular permeability and is a key mechanism for the development of enteric infections and inflammatory bowel diseases (IBDs). METHODOLOGY AND PRINCIPAL FINDINGS: To study the in vivo effect of probiotic Escherichia coli Nissle 1917 (EcN) on the stabilization of the intestinal barrier under healthy conditions, germfree mice were colonized with EcN or K12 E. coli strain MG1655. IECs were isolated and analyzed for gene and protein expression of the tight junction molecules ZO-1 and ZO-2. Then, in order to analyze beneficial effects of EcN under inflammatory conditions, the probiotic was orally administered to BALB/c mice with acute dextran sodium sulfate (DSS) induced colitis. Colonization of gnotobiotic mice with EcN resulted in an up-regulation of ZO-1 in IECs at both mRNA and protein levels. EcN administration to DSS-treated mice reduced the loss of body weight and colon shortening. In addition, infiltration of the colon with leukocytes was ameliorated in EcN inoculated mice. Acute DSS colitis did not result in an anion secretory defect, but abrogated the sodium absorptive function of the mucosa. Additionally, intestinal barrier function was severely affected as evidenced by a strong increase in the mucosal uptake of Evans blue in vivo. Concomitant administration of EcN to DSS treated animals resulted in a significant protection against intestinal barrier dysfunction and IECs isolated from these mice exhibited a more pronounced expression of ZO-1. CONCLUSION AND SIGNIFICANCE: This study convincingly demonstrates that probiotic EcN is able to mediate up-regulation of ZO-1 expression in murine IECs and confer protection from the DSS colitis-associated increase in mucosal permeability to luminal substances.
2007-01-01T00:00:00Z
Type I interferon drives tumor necrosis factor-induced lethal shock.
Huys, Liesbeth
Van Hauwermeiren, Filip
Dejager, Lien
Dejonckheere, Eline
Lienenklaus, Stefan
Weiss, Siegfried
Leclercq, Georges
Libert, Claude
http://hdl.handle.net/10033/87237
2019-08-30T11:35:14Z
2009-08-31T00:00:00Z
Type I interferon drives tumor necrosis factor-induced lethal shock.
Huys, Liesbeth; Van Hauwermeiren, Filip; Dejager, Lien; Dejonckheere, Eline; Lienenklaus, Stefan; Weiss, Siegfried; Leclercq, Georges; Libert, Claude
Tumor necrosis factor (TNF) is reputed to have very powerful antitumor effects, but it is also a strong proinflammatory cytokine. Injection of TNF in humans and mice leads to a systemic inflammatory response syndrome with major effects on liver and bowels. TNF is also a central mediator in several inflammatory diseases. We report that type I interferons (IFNs) are essential mediators of the lethal response to TNF. Mice deficient in the IFN-alpha receptor 1 (IFNAR-1) or in IFN-beta are remarkably resistant to TNF-induced hypothermia and death. After TNF injection, IFNAR-1(-/-) mice produced less IL-6, had less bowel damage, and had less apoptosis of enterocytes and hepatocytes compared with wild-type (WT) mice. Extensive gene expression analysis in livers of WT and IFNAR-1(-/-) mice revealed a large deficiency in the response to TNF in the knockout mice, especially of IFN-stimulated response element-dependent genes, many of which encode chemokines. In livers of IFNAR-1(-/-) mice, fewer infiltrating white blood cells (WBCs) were detected by immunohistochemistry. Deficiency of type I IFN signaling provided sufficient protection for potentially safer therapeutic use of TNF in tumor-bearing mice. Our data illustrate that type I IFNs act as essential mediators in TNF-induced lethal inflammatory shock, possibly by enhancing cell death and inducing chemokines and WBC infiltration in tissues.
2009-08-31T00:00:00Z