Lactococcus lactis carrying the pvalac dna expression vector coding for il-10 reduces inflammation in two murine models of experimental colitis

ZURITA-TURK, M.; DEL CARMEN, S.; GOMES SANTOS, C.A.; PROSPERI DE CASTRO, C.; BASTOS PEREIRA, V.; SOUZA, B.M.; AZEVEDO, M.; DE MORENO DE LEBLANC, A.; AZEVEDO, V.; LEBLANC, J.G.; MIYOSHI, A.

Egmond aan Zee

Simposio; 11th International Symposium on Lactic Acid Bacteria; 2014

Interleukin-10 (IL-10) is one of the most important anti-inflammatory cytokines involved in the intestinal immune response and its absence is related to inflammatory bowel diseases (IBD). However, oral treatment with IL-10 is limited due to its extreme sensitivity and survival in the gastrointestinal tract, and systemic treatments are hindered by IL-10?s short half-life and undesirable side effects. In this context, the aim of this work was to evaluate the anti-inflammatory effect of two Lactococcus lactis (LL) strains: LL MG1363 (wild-type) and LL MG1363 FnBPA [capable of delivering a eukaryotic expression vector (pValac) coding for murine IL-10 to eukaryotic cells] as a new strategy for the prevention of IBD in two mouse models [Dextran sulfate sodium (DSS)-induced and Trinitrobenzenesulfonic acid (TNBS)-induced]. The pValac:IL-10 plasmid was firstly constructed and its functionality was confirmed by evaluating the expression and secretion of IL-10 by transfected eukaryotic cells. Mice from the DSS and TNBS models received, by gavage, bacterial supplementation (109 UFC/mouse/day) of LL MG1363 (wt), LL MG1363 (pValac:IL-10), LL MG1363 FnBPA (wt), LL MG1363 FnBPA (pValac:IL-10) or saline solution (control and DSS or TNBS groups). On sacrification day, large intestines were removed, visually inspected for macroscopic evaluation and prepared for histological evaluation, cytokine and secretory IgA analysis. Overall, mice from the pValac:IL-10 groups showed statistically lower damage scores in their intestines (both at macroscopic and microscopic levels), higher IL-10 and lower TNF-α, IL-6 and IL-17 levels (DSS assay), and decreased IL-17 and IFN-γ levels (TNBS assay), compared to mice from the control and wt-groups, showing that administration of these two LL strains containing the pValac:IL-10 plasmid was effective in the prevention of inflammation in two murine models of IBD.