Salmon nasal cartilage proteoglycan up-regulates Listeria monocytogenes-mediated immune response in mice

Proteoglycan (PG) is a complex glycohydrate that is widely distributed in the extracellular matrix. We have reported that daily oral administration of PG extracted from salmon (Oncorhynchus keta) nasal cartilage modulates the severity and proinflammatory cytokine responses in Escherichia coli-stimulated macrophages, and attenuates mouse models of various inflammatory diseases. Thus, PG has shown anti-inflammatory activities. In this study, we investigated the effect of salmon nasal cartilage PG on a bacterial infection by using a mouse model of infection with Listeria monocytogenes, which is a facultative intracellular pathogen. PG enhanced production of cytokines including TNF-α, IL-6, IL-12 and IL-10 by heat-killed L. monocytogenes in macrophages and dendritic cells. Daily oral administration of PG inhibited proliferation of L. monocytogenes in the livers of infected mice. IFN-γ and IL-12 production was enhanced in the PG-treated mice. Uptake of L. monocytogenes cells by PG-treated macrophages was decreased, followed reduction of intracellular bacteria growth. Differential proteomic analysis of mouse liver revealed that positive and negative immunological molecules for host defense against L. monocytogenes infection were modulated by PG treatment. These results demonstrated that PG can activate immune responses for host defense against L. monocytogenes infection through augmentation of cytokines and limiting infection of macrophages. The present study indicates that PG possesses quite different potentials, depending on the host conditions.