BACKGROUND: Genetically modified Lactococcus lactis secreting interleukin-10 (IL-10) has been demonstrated to provide localized delivery of a therapeutic agent through active in situ synthesis in murine colitis. At present, many aspects of the exact mechanism by which the beneficial effect of the IL-10-producing L. lactis on the mucosa is mediated remain to be clarified. METHODS: Our aim was to determine the interaction of L. lactis with the intestinal mucosa. Therefore, we administered IL-10-producing L. lactis to healthy mice and in 2 mouse models of chronic colitis. Paraffin sections of ileum and colon samples were examined with confocal and transmission electron microscopy. Ileum and colon homogenates were prepared after flushing and after removal of mucus layer and epithelium. These homogenates and homogenates of mesenteric lymph nodes and spleen were plated on agar and immunoblotting for L. lactis and IL-10 was performed. RESULTS: Both confocal and electron microscopy showed the presence of lactococci in inflamed intestinal mucosa of mice with colitis. We recovered viable bacteria that could still produce IL-10 from homogenates of inflamed ileum and colon of which mucous and epithelial layers were removed. We did not find lactococci in mesenteric lymph nodes or in the spleen of mice with colitis. CONCLUSIONS: This study demonstrates uptake of IL-10-secreting L. lactis by the paracellular route in inflamed mucosal tissue. We suggest that IL-10 production by L. lactis residing inside the mucosa in the vicinity of responsive cells can improve the local action of interleukin-10 in inflamed tissue and the efficiency of the treatment.
BACKGROUND: Genetically modified Lactococcus lactis secreting interleukin-10 (IL-10) has been demonstrated to provide localized delivery of a therapeutic agent through active in situ synthesis in murinecolitis. At present, many aspects of the exact mechanism by which the beneficial effect of the IL-10-producing L. lactis on the mucosa is mediated remain to be clarified. METHODS: Our aim was to determine the interaction of L. lactis with the intestinal mucosa. Therefore, we administered IL-10-producing L. lactis to healthy mice and in 2 mouse models of chronic colitis. Paraffin sections of ileum and colon samples were examined with confocal and transmission electron microscopy. Ileum and colon homogenates were prepared after flushing and after removal of mucus layer and epithelium. These homogenates and homogenates of mesenteric lymph nodes and spleen were plated on agar and immunoblotting for L. lactis and IL-10 was performed. RESULTS: Both confocal and electron microscopy showed the presence of lactococci in inflamed intestinal mucosa of mice with colitis. We recovered viable bacteria that could still produce IL-10 from homogenates of inflamed ileum and colon of which mucous and epithelial layers were removed. We did not find lactococci in mesenteric lymph nodes or in the spleen of mice with colitis. CONCLUSIONS: This study demonstrates uptake of IL-10-secreting L. lactis by the paracellular route in inflamed mucosal tissue. We suggest that IL-10 production by L. lactis residing inside the mucosa in the vicinity of responsive cells can improve the local action of interleukin-10 in inflamed tissue and the efficiency of the treatment.
Authors: Julie Mirpuri; Ilya Sotnikov; Loren Myers; Timothy L Denning; Felix Yarovinsky; Charles A Parkos; Patricia W Denning; Nancy A Louis Journal: PLoS One Date: 2012-12-18 Impact factor: 3.240
Authors: Inge L Huibregtse; Sebatian A Zaat; Martien L Kapsenberg; Maria A Sartori da Silva; Maikel P Peppelenbosch; Sander J H van Deventer; Henri Braat Journal: Gastroenterol Res Pract Date: 2011-07-27 Impact factor: 2.260
Authors: Alejandra de Moreno de Leblanc; Silvina Del Carmen; Meritxell Zurita-Turk; Clarissa Santos Rocha; Maarten van de Guchte; Vasco Azevedo; Anderson Miyoshi; Jean Guy Leblanc Journal: ISRN Gastroenterol Date: 2011-02-08