Participation of glutathione in the elimination of Porphyromonas gingivalis in vivo.

Abstract

Introduction: Glutathione is involved in immune responses such as cell proliferation and bactericidal activity. The aim of this study was to see whether glutathione influences the intraperitoneal elimination of Porphyromonas gingivalis in Fusobacterium nucleatum-immunized mice.

Methods: Mice were immunized with P. gingivalis or F. nucleatum, and then P. gingivalis was inoculated into the peritoneal cavity of the mice. After various lengths of time, the numbers of bacteria were determined by a colony-forming assay and by polymerase chain reaction. The effect of glutathione on the elimination of P. gingivalis was explored by changing the intracellular glutathione level. Furthermore, we examined the effects of glutathione on the peritoneal levels of interferon-gamma, a macrophage activator, and of nitrite, a derivative of nitric oxide that acts as an antimicrobial agent when produced by macrophages and neutrophils.

Results: Inoculated P. gingivalis was eliminated more rapidly from F. nucleatum-immunized mice than from P. gingivalis-immunized mice. Interferon-gamma levels in peritoneal lavage fluid and glutathione levels in peritoneal exudate cells were higher in F. nucleatum-immunized mice than in P. gingivalis-immunized mice. When P. gingivalis-immunized mice were given glutathione monoethylester (a derivative of glutathione that is converted to glutathione intracellularly through hydrolysis) into the peritoneal cavity, the elimination of P. gingivalis was accelerated. On the other hand, when F. nucleatum-immunized mice were given L-buthionine-[S,R]-sulfoximine (an inhibitor of glutathione synthesis) into the peritoneal cavity, the elimination of P. gingivalis was suppressed.

Conclusion: In F. nucleatum-immunized mice, glutathione may have a key role in the defense against P. gingivalis infections.