@article{oai:soar-ir.repo.nii.ac.jp:00018017,
 author = {Shigemori,  Suguru and Watanabe,  Takafumi and Kudoh,  Kai and Ihara,  Masaki and Nigar,  Shireen and Yamamoto,  Yoshinari and Suda,  Yoshihito and Sato,  Takashi and Kitazawa,  Haruki and Shimosato,  Takeshi},
 journal = {MICROBIAL CELL FACTORIES},
 month = {Nov},
 note = {Background: Mucosal delivery of therapeutic proteins using genetically modified strains of lactic acid bacteria (gmLAB) is being investigated as a new therapeutic strategy. Methods: We 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). Results: We 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-1 alpha and IL-6 in the colon compared to a vector control strain. Conclusions: Oral 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., Article, MICROBIAL CELL FACTORIES. 14:189 (2015)},
 title = {Oral delivery of Lactococcus lactis that secretes bioactive heme oxygenase-1 alleviates development of acute colitis in mice},
 volume = {14},
 year = {2015}
}