Nasally Administered Lactococcus lactis Secreting Heme Oxygenase-1 Attenuates Murine Emphysema

Antioxidants

卷:9

Suguru Shigemori¹  Takeshi Shimosato¹  Fu Namai¹  Kentaro Yumoto²  Takeshi Kaneko²  Kentaro Nakashima²  Takashi Sato² 

[1] Department of Biomolecular Innovation, Institute for Biomedical Sciences, Shinshu University, Nagano 399-4598, Japan;

[2] Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan;

关键词: heme oxygenase-1;    Lactococcus lactis;    emphysema;    chronic obstructive pulmonary disease;   

DOI  :  10.3390/antiox9111049

来源: DOAJ

【 摘 要 】

Emphysema, a type of lung-destroying condition associated with chronic obstructive pulmonary disease (COPD), is an inflammatory lung disease mainly due to cigarette smoke exposure. As there is no curative therapy, prevention should be considered first by cessation of smoking to avoid exposure to oxidative stresses and inflammatory mediators. In addition, therapies involving antioxidative and/or anti-inflammatory agents such as heme oxygenase (HO)-1 are candidate treatments. We developed a new tool using genetically modified Lactococcus lactis to deliver recombinant HO-1 to the lungs. Using an elastase-induced emphysema model mimicking COPD, we evaluated the effect of nasally administered L. lactis secreting HO-1 (HO-1 lactis) on cellular and molecular responses in the lungs and further disease progression. Nasally administered HO-1 lactis resulted in (1) overexpression of HO-1 in the lungs and serum and (2) attenuation of emphysema progression evaluated both physiologically and morphologically. There was a transient 5–10% weight loss compared to baseline through trafficking to the lungs when administering 1.0 × 10⁹ cells/mouse; however, this did not impact either survival or final body weight. These results suggest that delivering HO-1 using genetically modified L. lactis through the airways could be a safe and potentially effective therapeutic approach for COPD.

【 授权许可】

Unknown