Anti-inflammatory and antioxidative effects of heat-killed Lactococcus lactis KC24 via modulation of NF-κB and Nrf2 pathways in HO-stressed A549 cells.

Oxidative stress can contribute to various chronic diseases due to the excessive accumulation of reactive oxygen species (ROS). The lungs are particularly vulnerable to oxidative stress caused by environmental and intrinsic factors, and likely to cause asthma, chronic obstructive pulmonary disease, and lung cancer. Lactococcus lactis KC24, isolated from kimchi, has been reported to exert neuroprotective effects as a heat-killed paraprobiotic. In this study, we investigated the anti-inflammatory and antioxidant properties of heat-killed L. lactis KC24 in HO-stimulated human pulmonary epithelial cells (A549). The results showed that HO significantly reduced cell viability and increased ROS generation. However, treatment with L. lactis KC24 significantly reduced ROS levels and improved cell viability more effectively than treatment with the commercial control (Lacticaseibacillus rhamnosus GG). Quantitative real-time polymerase chain reaction and western blotting results indicated that L. lactis KC24 downregulated the expression of pro-inflammatory cytokines (tumor necrosis factor-α, interleukin [IL]-6, and IL-8) and suppressed the activation of the nuclear factor-κB pathway. Furthermore, L. lactis KC24 increased the expression of nuclear factor erythroid-related factor 2 (Nrf2) and its associated antioxidant genes (heme oxygenase-1 [HO-1], NAD(P)H: quinone oxidoreductase 1, and thioredoxin reductase 1). L. lactis KC24 treatment also enhanced the transcript levels of Nrf2 and protein expression levels of HO-1. These results suggest that heat-killed L. lactis KC24 exhibits potent anti-inflammatory and antioxidant effects in HO-stressed human pulmonary epithelial cells, indicating its potential as a functional food for respiratory health management.