Yumoto Kentaro, Sato Takashi, Nakashima Kentaro, Namai Fu, Shigemori Suguru, Shimosato Takeshi, Kaneko Takeshi
Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
Department of Biomolecular Innovation, Institute for Biomedical Sciences, Shinshu University, Nagano 399-4598, Japan.
Antioxidants (Basel). 2020 Oct 27;9(11):1049. doi: 10.3390/antiox9111049.
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 to deliver recombinant HO-1 to the lungs. Using an elastase-induced emphysema model mimicking COPD, we evaluated the effect of nasally administered 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 × 10 cells/mouse; however, this did not impact either survival or final body weight. These results suggest that delivering HO-1 using genetically modified through the airways could be a safe and potentially effective therapeutic approach for COPD.
肺气肿是一种与慢性阻塞性肺疾病（COPD）相关的肺组织破坏病症，是一种主要由接触香烟烟雾引起的炎症性肺病。由于尚无治愈性疗法，首先应考虑通过戒烟来预防，以避免暴露于氧化应激和炎症介质。此外，涉及抗氧化剂和/或抗炎剂（如血红素加氧酶（HO）-1）的疗法是候选治疗方法。我们开发了一种利用基因改造的工具，将重组HO-1递送至肺部。使用模拟COPD的弹性蛋白酶诱导的肺气肿模型，我们评估了经鼻给药分泌HO-1的乳酸乳球菌（HO-1 lactis）对肺部细胞和分子反应以及疾病进一步进展的影响。经鼻给药HO-1 lactis导致（1）肺部和血清中HO-1的过表达，以及（2）从生理和形态学上评估的肺气肿进展的减轻。当以1.0×10个细胞/小鼠给药时，与基线相比，通过转运至肺部会出现短暂5-10%的体重减轻；然而，这既不影响生存率也不影响最终体重。这些结果表明，通过气道利用基因改造的乳酸乳球菌递送HO-1可能是一种安全且潜在有效的COPD治疗方法。
