Joerg Emmrich

Publications of Joerg Emmrich

• Bacterial Immunotherapy-Antitumoral Potential of the Streptococcal Toxin Streptolysin S-

  Authors: Claudia Maletzki, Bernd Kreikemeyer, Peggy Bodammer, Joerg Emmrich, Michael Linnebacher

  03/2012;

  ISBN: 978-953-51-0394-3

• Prophylactic application of bovine colostrum ameliorates murine colitis via induction of immunoregulatory cells.

  Authors: Peggy Bodammer, Claudia Maletzki, Grit Waitz, Joerg Emmrich

  The Journal of nutrition. 06/2011; 141(6):1056-61.

  Epidemiologic studies suggest a relationship between early weaning and the incidence of inflammatory bowel disease. Herein, we addressed the question whether bovine colostrum, the first milk producedEpidemiologic studies suggest a relationship between early weaning and the incidence of inflammatory bowel disease. Herein, we addressed the question whether bovine colostrum, the first milk produced by mammals, is able to prevent dextran sulfate sodium (DSS)-induced colitis in mice. Prior to induction of colitis with 5% DSS, Naval Medical Research Institute mice were fed bovine colostrum [BV-20 or 200 mg/kg body weight (BW)], BSA (20 mg/kg BW), or water (100 μL) daily by oral gavage for 2 wk. The clinical severity of colitis was determined by scoring changes in BW and colon length reduction. Following 2 wk of observation, the colons were removed for histologic and immunohistochemical evaluation of inflammation. Flow cytometric phenotyping of leukocyte subsets was performed from peripheral blood, mesenteric lymph nodes, and spleens. Administration of bovine colostrum improved the clinical and histologic severity of colorectal inflammation. Compared with BSA-fed and water-fed controls, BV-20 pretreated mice had significantly less severe weight loss and decreased colon shortening. Beneficial effects were accompanied by redistribution of immunoregulatory, peripheral and splenic γδ TCR(+) cells, and CD11b(+)Gr1(+) cells. Higher colostrum doses did not affect disease activity. In summary, prophylactic administration of colostrum improved clinical symptoms of colorectal inflammation in a well-established mouse model of DSS-induced colitis. Further investigations will target the underlying immunomodulatory mechanisms to our approach.

• Schistosoma mansoni infection but not egg antigen promotes recovery from colitis in outbred NMRI mice.

  Authors: Peggy Bodammer, Grit Waitz, Micha Loebermann, Martha Charlotte Holtfreter, Claudia Maletzki, Marzena Renata Krueger, Horst Nizze, Joerg Emmrich, Emil Christian Reisinger

  Digestive diseases and sciences. 01/2011; 56(1):70-8.

  The ability of intestinal helminths to manipulate the immune system of their host towards a Th2 response has been proposed to modulate auto-immune and allergic diseases. This initial studyThe ability of intestinal helminths to manipulate the immune system of their host towards a Th2 response has been proposed to modulate auto-immune and allergic diseases. This initial study investigated the anti-inflammatory potential of S. mansoni and soluble egg antigen (SEA) in a murine model of colitis. Colitis was induced in female NMRI mice by 5% dextran sulfate sodium (DSS) for 7 days, either 9 weeks post-infection with S. mansoni or during treatment with SEA. In addition to clinical signs of colitis, colon histology, immunohistochemistry, and flow cytometry of leukocytes were performed. Colon cytokines were measured using a quantitative real-time technique. Infection with cercariae of S. mansoni attenuated DSS-induced colitis. Clinical symptoms such as weight loss and shortening of colon length were significantly prevented. Histological scores and cell infiltration were affected and expression of pro-inflammatory cytokines in the colons of infected DSS colitis mice was reduced. In contrast, application of SEA failed to improve colitis, even though some findings like earlier manifestation of inflammation and local induction of Th2 cytokines were similar to the effects of cercarial infection. The results presented here suggest that SEA treatment could not protect mice from acute colitis. However, both infection with S. mansoni and injection of SEA affect mucosal immune responses.

• cis-Hydroxyproline-mediated pancreatic carcinoma growth inhibition in mice.

  Authors: Dietrich Sturm, Claudia Maletzki, Dagmar Braun, Joerg Emmrich

  International journal of colorectal disease. 08/2010; 25(8):921-9.

  This study addressed the question of whether the collagen metabolism modulator cis-4-Hydroxy-L-proline (CHP) is applicable for potential use as a therapeutic inhibitor of pancreatic carcinoma cellThis study addressed the question of whether the collagen metabolism modulator cis-4-Hydroxy-L-proline (CHP) is applicable for potential use as a therapeutic inhibitor of pancreatic carcinoma cell growth. Cell proliferation, as well as quantification of apoptosis of murine Panc02 cells, was assessed after CHP treatment. Supplementary, the effect of CHP on tumor growth was examined in the subcutaneous Panc02 model in vivo. Mice received daily intraperitoneal injections of CHP (300, 400, and 500 mg/kg bw). In addition to the assessment of systemic parameters (blood count, enzyme activities), histology (HE) and immunohistochemistry (Ki-67) were performed from resected tumor specimens. Like reduction of metabolic activity, CHP also induced inhibition of cell growth in a dose-dependent manner, with however only slight increases in apoptosis. In vivo treatment of Panc02 tumors with CHP resulted in pronounced delay of tumor growth and decreases in tumor cell proliferation. Moreover, these effects were accompanied by a massive systemic leukocytosis as well increased leukocyte infiltration into the tumors subsequent to CHP therapy. CHP inhibits the proliferation of Panc02 tumor cells in a dose-dependent manner both in vitro and in vivo. Our presented data show that modulation of the collagen metabolism is an interesting strategy for treatment of pancreatic carcinoma.

• Reduction of Dendritic Cells by Granulocyte and Monocyte Adsorption Apheresis in Patients with Ulcerative Colitis.

  Authors: Grit Waitz, Sebastian Petermann, Stefan Liebe, Joerg Emmrich, Wolfgang Ramlow

  Digestive diseases and sciences. 03/2008;

  The influence of the granulocyte/monocyte apheresis (GMCAP) on cell populations participating in mechanisms of tolerance, e.g. dendritic cells (DCs), is still not very clear. In a first step, weThe influence of the granulocyte/monocyte apheresis (GMCAP) on cell populations participating in mechanisms of tolerance, e.g. dendritic cells (DCs), is still not very clear. In a first step, we aimed to investigate changes in the DC population of patients suffering from ulcerative colitis (UC) (n = 13) compared to healthy subjects (n = 9). In a second step, we studied the changes in peripheral DCs in a small group of patients with active UC before and after Adacolumn apheresis (n = 7). For this purpose, plasmacytoid and myeloid DCs and their maturation markers CD40, CD80, and CD86 were measured using four-color flow cytometry in the peripheral blood. After apheresis, and in acute flare-ups, we identified a significantly lower number of lymphocytes, plasmacytoid, and myeloid DCs. In conclusion, the additional removal of peripheral DCs by GMCAP, which otherwise would contribute to the inflammatory process in the gut, may lead to a higher tolerogeneic status towards luminal antigens.

• Cis-hydroxyproline-induced inhibition of pancreatic cancer cell growth is mediated by endoplasmic reticulum stress.

  Authors: Christoph Mueller, Joerg Emmrich, Robert Jaster, Dagmar Braun, Stefan Liebe, Gisela Sparmann

  World journal of gastroenterology : WJG. 04/2006; 12(10):1569-76.

  AIM: To investigate the biological effects of cis-hydroxyproline (CHP) on the rat pancreatic carcinoma cell line DSL6A, and to examine the underlying molecular mechanisms. METHODS: The effect of CHPAIM: To investigate the biological effects of cis-hydroxyproline (CHP) on the rat pancreatic carcinoma cell line DSL6A, and to examine the underlying molecular mechanisms. METHODS: The effect of CHP on DSL6A cell proliferation was assessed by using BrdU incorporation. The expression of focal adhesion kinase (FAK) was characterized by Western blotting and immunofluorescence. Induction of endoplasmic reticulum (ER) stress was investigated by using RT-PCR and Western blotting for the glucose-related protein-78 (GRP78) and growth arrest and DNA inducible gene (GADD153). Cell viability was determined through measuring the metabolic activity based on the reduction potential of DSL6A cells. Apoptosis was analyzed by detection of caspase-3 activation and cleavage of poly(ADP-ribose) polymerase (PARP) as well as DNA laddering. RESULTS: In addition to inhibition of proliferation, incubation with CHP induced proteolytic cleavage of FAK and a delocalisation of the enzyme from focal adhesions, followed by a loss of cell adherence. Simultaneously, we could show an increased expression of GRP78 and GADD153, indicating a CHP-mediated activation of the ER stress cascade in the DSL6A cell line. Prolonged incubation of DSL6A cells with CHP finally resulted in apoptotic cell death. Beside L-proline, the inhibition of intracellular proteolysis by addition of a broad spectrum protease inhibitor could abolish the effects of CHP on cellular functions and the molecular processes. In contrast, impeding the activity of apoptosis-executing caspases had no influence on CHP-mediated cell damage. CONCLUSION: Our data suggest that the initiation of ER stress machinery by CHP leads to an activation of intracellular proteolytic processes, including caspase-independent FAK degradation, resulting in damaging pancreatic carcinoma cells.

• Immunologic characterization of acute pancreatitis in rats induced by dibutyltin dichloride (DBTC).

  Authors: Steffi Hense, Gisela Sparmann, Heike Weber, Stefan Liebe, Joerg Emmrich

  Pancreas. 08/2003; 27(1):e6-12.

  There is little information available regarding the role of inflammatory cells and cytokines in the pancreatic tissue during acute interstitial pancreatitis. The single intravenous application ofThere is little information available regarding the role of inflammatory cells and cytokines in the pancreatic tissue during acute interstitial pancreatitis. The single intravenous application of dibutyltin dichloride (DBTC) induces a pancreatitis in rats with a dosage dependent course. We analyzed the infiltrating leukocytes and the cytokine expression profile in the experimental model of DBTC-initiated mild interstitial pancreatitis during a time course of 4 weeks. Macrophages dominated among the infiltrating inflammatory cells detected by immunohistochemistry. The expression of IL-1beta, IL-10, and TGFbeta1 was shown to be elevated 24 hours after onset of pancreatitis reaching a maximum during the first week. Positive immunostaining of IL-1beta, IL-10, or TGFbeta1 was not restricted to infiltrating leukocytes but was found to various degrees in pancreatic cells. Transcripts of collagen type 1 reached high levels in the first week, but were down regulated thereafter. There was no significant expression of IL-2, IL-2 receptor, IL-4, TNFalpha, or IFNgamma. Our data show that the experimental interstitial pancreatitis was characterized by macrophage infiltration accompanied by elevated cytokine expression that lasted longer than the visible morphologic lesions. These inflammatory processes might create the environment that makes the pancreas more susceptible to further damaging effects.

• Screening for p53 and K-ras mutations in whole-gut lavage in chronic inflammatory bowel disease.

  Authors: Maria Heinzlmann, Susanne M Lang, Sven Neynaber, Max Reinshagen, Joerg Emmrich, Diana F Stratakis, Walter Heldwein, Baldur Wiebecke, Klaus Loeschke

  European journal of gastroenterology & hepatology. 10/2002; 14(10):1061-6.

  OBJECTIVES: Molecular screening for frequently mutated genes may increase the likelihood of identifying cancer risk groups, such as patients with longstanding inflammatory bowel disease. This studyOBJECTIVES: Molecular screening for frequently mutated genes may increase the likelihood of identifying cancer risk groups, such as patients with longstanding inflammatory bowel disease. This study investigated the prevalence and time course of p53 and K-ras mutations in colonic lavage fluid of patients with inflammatory bowel disease. METHODS: Colonic lavage fluid from 190 patients with ulcerative colitis (73), Crohn's disease (58) or controls (49 non-tumour, 10 colorectal cancer) was studied by oligomer-specific hybridization for K-ras mutations and single-strand conformation polymorphism (SSCP) for p53 mutations. Follow-up investigations were carried out after 1-3 years. RESULTS: Mutations were most frequent in carcinomas (5/10, 50%) and rare in non-tumour controls (1/49, 2.0%). They were found in Crohn's colitis in 15.4%, in extensive ulcerative colitis in 18.6%, in left-sided ulcerative colitis in 13.3%, and in distal ulcerative colitis in 6.7% (P > 0.05). There was a positive association with disease duration (> or =11 years, P < 0.05). Follow-up investigations detected the same mutation in four patients and revealed new mutations in three patients. CONCLUSIONS: In our large series of patients with inflammatory bowel disease, K-ras and p53 mutations could be detected with reasonable frequency and confirmed at follow-up in at least some patients. Our data encourage the use of molecular screening for the detection of malignant precursor lesions in at-risk patients.