Open AccessEffect of a matrix metalloproteinase inhibitor on host resistance against Listeria monocytogenes infection
Author(s) -
Yamada Kyogo,
Yoshino Kohichiro,
Sekikawa Kenji,
Madarame Hiroo,
Yagita Hideo,
Nakane Akio
Publication year - 2000
Publication title -
fems immunology & medical microbiology
Language(s) - English
Resource type - Journals
eISSN - 1574-695X
pISSN - 0928-8244
DOI - 10.1111/j.1574-695x.2000.tb01522.x
Subject(s) - listeria monocytogenes , biology , microbiology and biotechnology , host (biology) , matrix metalloproteinase , matrix (chemical analysis) , bacteria , virology , genetics , chemistry , chromatography
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‐α (TNF‐α) 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‐α 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‐α production in spleen cell cultures stimulated by heat‐killed L. monocytogenes and the drug treatment reduced serum TNF‐α levels in infected mice, whereas the compound was ineffective on the modulation of interferon‐γ and interleukin‐10 production. The effect of KB‐R7785 was considered to be dependent on TNF‐α because the drug failed to affect L. monocytogenes infection in anti‐TNF‐α monoclonal antibody‐treated mice and TNF‐α knockout mice. Anti‐CD95L monoclonal antibody was also ineffective on the infection. These results suggest that induction of infectious diseases, to which TNF‐α is critical in host resistance, should be considered in MMP inhibitor‐treated hosts.