Effect of a matrix metalloproteinase inhibitor on host resistance against Listeria monocytogenes infection.

Abstract

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.

• Authors: K Yamada, K Yoshino, K Sekikawa, H Madarame, H Yagita, A Nakane
• Journal: FEMS immunology and medical microbiology (FEMS Immunol Med Microbiol) Vol. 29 Issue 3 Pg. 187-94 (Nov 2000) ISSN: 0928-8244 [Print] England
• PMID: 11064265 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Fas Ligand Protein
• Fasl protein, mouse
• Hydroxamic Acids
• KB R7785
• Lipopolysaccharides
• Matrix Metalloproteinase Inhibitors
• Membrane Glycoproteins
• Protease Inhibitors
• Tumor Necrosis Factor-alpha
• Glycine

Topics

• Animals
• Antibodies, Monoclonal
• Colony Count, Microbial
• Fas Ligand Protein
• Female
• Glycine (analogs & derivatives, pharmacology)
• Hydroxamic Acids (pharmacology)
• Immunity, Innate
• Lipopolysaccharides
• Listeriosis (immunology, metabolism)
• Matrix Metalloproteinase Inhibitors
• Membrane Glycoproteins (antagonists & inhibitors)
• Mice
• Mice, Inbred C57BL
• Protease Inhibitors (pharmacology)
• Shock, Septic (mortality, prevention & control)
• Spleen (metabolism)
• Tumor Necrosis Factor-alpha (antagonists & inhibitors, biosynthesis)