title: Protective effects of lactococci strains delivering either IL-10 protein or cDNA in a TNBS-induced chronic colitis model.
abstract: BACKGROUND
  Oral treatment with Lactococcus lactis strains secreting the anti-inflammatory cytokine interleukin (IL)-10 has previously shown success as a therapy for inflammatory bowel diseases (IBD).
  
  
  OBJECTIVE
  Our aim was to compare the protective effects of IL-10, delivered by recombinant lactoccoci using 2 novel expression systems, in a murine colitis model mimicking the relapsing nature of IBD. The first system is based on a Stress-Inducible Controlled Expression system for the production and delivery of heterologous proteins at mucosal surfaces and the second allows the delivery to the host cells of an il-10 cDNA cassette, harbored in a eukaryotic DNA expression vector (pValac).
  
  
  METHODS
  Colitis was induced in female BALB/c mice by intrarectal injection of 2,4,6-trinitrobenzenesulphonic acid (TNBS). Mice that recovered received one of the bacteria treatments or saline solution orally during 14 days. Colitis was reactivated 25 days after the first TNBS injection with a second TNBS challenge. Three days after colitis reactivation, cytokine profiles and inflammation in colon samples were evaluated.
  
  
  RESULTS
  Animals (N=9) receiving L. lactis strains secreting IL-10 using Stress-Inducible Controlled Expression system or delivering pValac:il-10 plasmid showed lower weight loss (P<0.005), lower damage scores (P<0.005), and immune activation in their large intestines compared with inflamed nontreated mice.
  
  
  CONCLUSIONS
  Our results confirm the protective effect of IL-10 delivered either as a protein or as a cDNA in a colitis model mimicking the relapsing nature of IBD and provides a step further in the "proof-of-concept" of genetically engineered bacteria as a valid system to deliver therapeutic molecules at mucosal level.
authors.affiliation: *Centro de Referencia para Lactobacilos (CERELA-CONICET), San Miguel de Tucumán, Argentina (T4000ILC) †INRA ‡AgroParisTech, UMR Micalis, Jouy-en-Josas, France §Institute of Biological Sciences, Federal University of Minas Gerais (UFMG-ICB), Belo Horizonte, MG, Brazil.
authors.forename: Silvina
authors.initials: S
authors.lastname: del Carmen
authors.forename: Rebeca
authors.initials: R
authors.lastname: Martín Rosique
authors.forename: Tessália
authors.initials: T
authors.lastname: Saraiva
authors.forename: Meritxell
authors.initials: M
authors.lastname: Zurita-Turk
authors.forename: Anderson
authors.initials: A
authors.lastname: Miyoshi
authors.forename: Vasco
authors.initials: V
authors.lastname: Azevedo
authors.forename: Alejandra
authors.initials: A
authors.lastname: de Moreno de LeBlanc
authors.forename: Philippe
authors.initials: P
authors.lastname: Langella
authors.forename: Luis G
authors.initials: LG
authors.lastname: Bermúdez-Humarán
authors.forename: Jean Guy
authors.initials: JG
authors.lastname: LeBlanc
mesh_terms: D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control*; D003106:Colon / Q000276:immunology / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005822:Genetic Vectors; D018836:Inflammation Mediators / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D007778:Lactobacillus / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008807:Mice, Inbred BALB C; D019936:Probiotics; D012720:Severity of Illness Index; D013997:Time Factors; D014302:Trinitrobenzenesulfonic Acid; D015431:Weight Loss
chemical_list: D018836:Inflammation Mediators; D016753:Interleukin-10; D014302:Trinitrobenzenesulfonic Acid