Effect of a matrix metalloproteinase inhibitor on host resistance againstListeria monocytogenesinfection
Copyright policy )Effect of a matrix metalloproteinase inhibitor on host resistance againstListeria monocytogenesinfection
Hydroxy acid-based matrix metalloproteinase (MMP) inhibitors have been shown to inhibit tumor infiltration and growth, endotoxin shock, and acute graft-versus-host disease. Blockade of the release of soluble tumor necrosis factor-alpha (TNF-alpha) and CD95 ligand (CD95L; FasL) from cell-associated forms is reportedly involved in the mechanism of the drug effect. We investigated the effect of a MMP inhibitor, KB-R7785, on host resistance against Listeria monocytogenes infection, in which TNF-alpha is essentially required for the defense, in mice. The administration of KB-R7785 exacerbated listeriosis, while the drug prevented lethal shock induced by lipopolysaccharide and D-galactosamine. KB-R7785 inhibited soluble TNF-alpha production in spleen cell cultures stimulated by heat-killed L. monocytogenes and the drug treatment reduced serum TNF-alpha levels in infected mice, whereas the compound was ineffective on the modulation of interferon-gamma and interleukin-10 production. The effect of KB-R7785 was considered to be dependent on TNF-alpha because the drug failed to affect L. monocytogenes infection in anti-TNF-alpha monoclonal antibody-treated mice and TNF-alpha knockout mice. Anti-CD95L monoclonal antibody was also ineffective on the infection. These results suggest that induction of infectious diseases, to which TNF-alpha is critical in host resistance, should be considered in MMP inhibitor-treated hosts.
- Juntendo University Japan
- Azabu University Japan
- Hirosaki University Japan
Lipopolysaccharides, Fas Ligand Protein, Membrane Glycoproteins, Tumor Necrosis Factor-alpha, Colony Count, Microbial, Glycine, Antibodies, Monoclonal, Matrix Metalloproteinase Inhibitors, Hydroxamic Acids, Shock, Septic, Immunity, Innate, Mice, Inbred C57BL, Mice, Animals, Female, Listeriosis, Protease Inhibitors, Spleen
Lipopolysaccharides, Fas Ligand Protein, Membrane Glycoproteins, Tumor Necrosis Factor-alpha, Colony Count, Microbial, Glycine, Antibodies, Monoclonal, Matrix Metalloproteinase Inhibitors, Hydroxamic Acids, Shock, Septic, Immunity, Innate, Mice, Inbred C57BL, Mice, Animals, Female, Listeriosis, Protease Inhibitors, Spleen
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