Pasteurellosis caused by Pasteurella multocida manifest often as respiratory
infection in farmed small ruminants. Although the incidence of
pasteurellosis due to P. multocida mainly takes the form of
pneumonia, there is limited information on host factors that play a role in disease pathogenesis in the milieu of host-pathogen interactions. Nuclear factor-erythroid 2 related factor 2 (Nrf-2), a critical regulator for various inflammatory and immune responses by controlling oxidative stress, may play an important role in the processes of
inflammation induced by P. multocida. In this study,
linalool, a natural compound of the
essential oils in several aromatic plant species, elevated nuclear Nrf-2 protein translocation in the A549 lung cell line and in vivo. The P. multocida-induced pro-inflammatory
cytokines expression was abrogated by Nrf-2
siRNA. Postponed treatment with
linalool decreased lung neutrophil accumulation and enhanced clearance of P. multocida. Furthermore,
linalool significantly increased the expression of
antioxidant enzymes regulated by Nrf-2 and diminished lung tissue levels of several pro-inflammatory
cytokines, including
tumor necrosis factor α (TNF-α) and
interleukin (IL)-6. In addition, animals treated with
linalool had a marked improvement in survival. These findings have uncovered that
linalool acts as a novel Nrf-2 activator for a novel therapeutic strategy in pathogen-mediated
lung inflammation.