title: Dextran sulphate sodium colitis in C57BL/6J mice is alleviated by Lactococcus lactis and worsened by the neutralization of Tumor necrosis Factor α.
abstract: TNFα has a well-established role in inflammatory bowel disease that affects the gastrointestinal tract and is usually manifested as Crohn's disease or ulcerative colitis. We have compared Lactococcus lactis NZ9000 displaying TNFα-binding affibody with control Lactococcus lactis and with anti-TNFα antibody infliximab for the treatment of mice with dextran sulphate sodium (DSS)-induced colitis. L. lactis NZ9000 alleviated the colitis severity one week after colitis induction with DSS, more effectively when administered in preventive fashion prior to, during and after DSS administration. TNFα-binding L. lactis was less effective than control L. lactis, particularly when TNFα-binding L. lactis was administered in preventive fashion. Similarly, an apparently detrimental effect of TNFα neutralization was observed in mice that were intraperitoneally administered anti-TNFα monoclonal antibody infliximab prior to colitis induction. The highest concentrations of tissue TNFα were observed in groups without DSS colitis that were treated either with TNFα-binding L. lactis or infliximab. To conclude, we have confirmed that L. lactis exerts a protective effect on DSS-induced colitis in mice. Contrary to expectations, but in line with some reports, the neutralization of TNFα aggravated disease symptoms in the acute phase of colitis and increased TNFα concentration in colon tissue of healthy mice. Nevertheless, we have demonstrated that oral administration of bacteria with surface displayed TNFα-binding affibody can interfere significantly with TNFα signaling and mimic the infliximab response in the given animal model of colitis.
authors.affiliation: Department of Biotechnology, Jožef Stefan Institute, Jamova 39, SI-1000 Ljubljana, Slovenia. Electronic address: ales.berlec@ijs.si.
authors.forename: Aleš
authors.initials: A
authors.lastname: Berlec
authors.affiliation: Institute of Pathology, Medical Experimental Centre, Faculty of Medicine, University of Ljubljana, Zaloška 4, 1000 Ljubljana, Slovenia.
authors.forename: Martina
authors.initials: M
authors.lastname: Perše
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia.
authors.forename: Matjaž
authors.initials: M
authors.lastname: Ravnikar
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia.
authors.forename: Mojca
authors.initials: M
authors.lastname: Lunder
authors.affiliation: Institute of Cell Biology, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia.
authors.forename: Andreja
authors.initials: A
authors.lastname: Erman
authors.affiliation: Institute of Pathology, Medical Experimental Centre, Faculty of Medicine, University of Ljubljana, Zaloška 4, 1000 Ljubljana, Slovenia.
authors.forename: Anton
authors.initials: A
authors.lastname: Cerar
authors.affiliation: Department of Biotechnology, Jožef Stefan Institute, Jamova 39, SI-1000 Ljubljana, Slovenia; Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia.
authors.forename: Borut
authors.initials: B
authors.lastname: Štrukelj
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D057134:Antibodies, Neutralizing / Q000737:chemistry / Q000627:therapeutic use*; D003092:Colitis / Q000139:chemically induced / Q000628:therapy*; D003106:Colon / Q000187:drug effects* / Q000276:immunology; D016264:Dextran Sulfate; D005260:Female; D006801:Humans; D000069285:Infliximab / Q000627:therapeutic use*; D007413:Intestinal Mucosa / Q000187:drug effects*; D013294:Lactococcus lactis / Q000737:chemistry / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D057134:Antibodies, Neutralizing; D014409:Tumor Necrosis Factor-alpha; D016264:Dextran Sulfate; D000069285:Infliximab
keywords: Colitis; DSS model; Lactococcus lactis; Mice; TNFα neutralization