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

Abstract

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.

Oral and Intranasal Immunization with Recombinant Food-Grade Lactococcus Lactis Expressing High Conserved Region of SARS-CoV-2 Spike Protein Triggers Immunity Responses in Mice

“…This L. Lactis vaccine is food grade and safer because it uses a lactose selection system and does not use antibiotics. L. lactis has been widely tested as a therapeutic career [10,11], including in vaccine delivery systems [7,12]. This microbe-based vaccine is highly suitable when administered via the intranasal and oral routes, which is in line with the results of this study.…”

Carboxymethyl Chitosan Modified Oxymatrine Liposomes for the Alleviation of Emphysema in Mice via Pulmonary Administration

“…In terms of oxidative stress, Nrf2, as a nuclear transcription activator, regulated the induction of defensive genes encoding the detoxifying enzymes and antioxidant proteins [ 51 ]. HO-1 is a downstream protein of Nrf2, which showed protective effects against oxidative stress [ 52 ]. According to the previous reports, decreased expression of Nrf2 was observed in the lung of emphysema patients, while the therapeutic regimens that maintained or promoted the level of Nrf2 was potential therapy for emphysema [ 53 ].…”

Plasmid Replicons for the Production of Pharmaceutical-Grade pDNA, Proteins and Antigens by Lactococcus lactis Cell Factories

“…In this study, IL-1Ra was secreted in a much higher amount (2 mg/L) when compared with other cytokines in previous studies. The same plasmid was used in a pioneer study [ 148 ] that showed that recombinant L. lactis can be administered nasally in order to deliver therapeutical molecules to the lungs, and further into the systemic circulation.…”