Oral delivery of Lactococcus lactis that secretes bioactive heme oxygenase-1 alleviates development of acute colitis in mice

Microbial Cell Factories

Research

Shireen Nigar¹  Yoshinari Yamamoto¹  Kai Kudoh¹  Masaki Ihara²  Takeshi Shimosato³  Suguru Shigemori⁴  Takafumi Watanabe⁵  Yoshihito Suda⁶  Takashi Sato⁷  Haruki Kitazawa⁸ 

[1] Department of Bioscience and Food Production Science, Interdisciplinary Graduate School of Science and Technology, Shinshu University, 8304 Minamiminowa, Kamiina, 399-4598, Nagano, Japan;Department of Bioscience and Food Production Science, Interdisciplinary Graduate School of Science and Technology, Shinshu University, 8304 Minamiminowa, Kamiina, 399-4598, Nagano, Japan;Department of Bioscience and Biotechnology, Graduate School of Agriculture, Shinshu University, 8304 Minamiminowa, Kamiina, 399-4598, Nagano, Japan;Department of Interdisciplinary Genome Sciences and Cell Metabolism, Institute for Biomedical Sciences (IBS), Interdisciplinary Cluster for Cutting Edge Research (ICCER), Shinshu University, 8304 Minamiminowa, Kamiina, 399-4598, Nagano, Japan;Department of Bioscience and Food Production Science, Interdisciplinary Graduate School of Science and Technology, Shinshu University, 8304 Minamiminowa, Kamiina, 399-4598, Nagano, Japan;Department of Interdisciplinary Genome Sciences and Cell Metabolism, Institute for Biomedical Sciences (IBS), Interdisciplinary Cluster for Cutting Edge Research (ICCER), Shinshu University, 8304 Minamiminowa, Kamiina, 399-4598, Nagano, Japan;Department of Sciences of Functional Foods, Graduate School of Agriculture, Shinshu University, 8304 Minamiminowa, Kamiina, 399-4598, Nagano, Japan;Department of Bioscience and Food Production Science, Interdisciplinary Graduate School of Science and Technology, Shinshu University, 8304 Minamiminowa, Kamiina, 399-4598, Nagano, Japan;Research Fellow of the Japan Society for the Promotion of Science, Japan Society for the Promotion of Science (JSPS), 5-3-1, Kojimachi, Chiyoda-ku, 102-0083, Tokyo, Japan;Department of Food Production Science, Graduate School of Agriculture, Shinshu University, 8304 Minamiminowa, Kamiina, 399-4598, Nagano, Japan;Department of Food, Agriculture and Environment, Miyagi University, 2-2-1 Hatadate, Taihaku-ku, 982-0215, Sendai, Miyagi, Japan;Department of Internal Medicine and Clinical Immunology, Graduate School of Medicine, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Kanagawa, Yokohama, 236-0004, Japan;Food and Feed Immunology Group, Graduate School of Agricultural Science, Tohoku University, 1-1 Tsutsumidori-Amamiyamachi, Aoba-ku, 981-8555, Sendai, Miyagi, Japan;Livestock Immunology Unit, International Education and Research Center for Food and Agricultural Immunology (CFAI), Graduate School of Agricultural Science, Tohoku University, 1-1 Tsutsumidori-Amamiyamachi, Aoba-ku, 981-8555, Sendai, Miyagi, Japan;

关键词: Lactococcus lactis;    Heme oxygenase-1;    Acute colitis;    Interleukin-10;    Mice;    Inflammatory bowel disease;   

DOI  :  10.1186/s12934-015-0378-2

 received in 2015-06-09, accepted in 2015-11-06,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundMucosal delivery of therapeutic proteins using genetically modified strains of lactic acid bacteria (gmLAB) is being investigated as a new therapeutic strategy.MethodsWe developed a strain of gmLAB, Lactococcus lactis NZ9000 (NZ-HO), which secretes the anti-inflammatory molecule recombinant mouse heme oxygenase-1 (rmHO-1). The effects of short-term continuous oral dosing with NZ-HO were evaluated in mice with dextran sulfate sodium (DSS)-induced acute colitis as a model of inflammatory bowel diseases (IBD).ResultsWe identified the secretion of rmHO-1 by NZ-HO. rmHO-1 was biologically active as determined with spectroscopy. Viable NZ-HO was directly delivered to the colon via oral administration, and rmHO-1 was secreted onto the colonic mucosa in mice. Acute colitis in mice was induced by free drinking of 3 % DSS in water and was accompanied by an increase in the disease activity index score and histopathological changes. Daily oral administration of NZ-HO significantly improved these colitis-associated symptoms. In addition, NZ-HO significantly increased production of the anti-inflammatory cytokine interleukin (IL)-10 and decreased the expression of pro-inflammatory cytokines such as IL-1α and IL-6 in the colon compared to a vector control strain.ConclusionsOral administration of NZ-HO alleviates DSS-induced acute colitis in mice. Our results suggest that NZ-HO may be a useful mucosal therapeutic agent for treating IBD.

【 授权许可】

CC BY   
© Shigemori et al. 2015