Chromosomal AmpC β-lactamase-mediated β-lactam resistance of gram-negative bacteria enhances host inflammatory mediator production via nucleotide-binding oligomerization domain 1
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概要
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Objective : We evaluated the impact of AmpC-overproducing mutant infection on host inflammatory mediator production. Materials and Methods : Wild-type and AmpC-overproducing mutant (AmpD mutant) Enterobacter cloacae strains were used to infect J774.1 macrophages. To deplete expression of nucleotide-binding oligomerization domain 1 (NOD1), J774.1 cells were transiently transfected with NOD1-specific siRNA. The induction of AmpC in the wild-type strain was performed by exposure to sub-minimum inhibitory concentration (MIC) imipenem for 2 hours. Levels of inflammatory mediators were measured by real-time PCR and ELISA. Results : At 4 hours after infection with the AmpD mutant, expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and macrophage inflammatory protein (MIP)-2 was significantly induced in J774.1 cells compared with the effect of infection by wild-type E. cloacae (P<0.05). Release of TNF-α, IL-1β, and MIP-2 from AmpD mutant-infected J774.1 cells was also significantly increased at 24 hours compared with the effect of wild-type E. cloacae (P<0.05). Infection of J774.1 cells with subMIC imipenem-treated wild-type E. cloacae also caused significant induction of the above mediators compared with the effect of untreated wild-type E. cloacae. The induction of inflammatory mediators was markedly diminished by the AmpD mutant or imipenem-treated strain infection of NOD1-silenced J774.1 cells. Conclusion : Our findings indicate that AmpC-mediated extended-spectrum cephalosporin resistance of E. cloacae enhances host inflammatory mediator production via NOD1.
- 北里大学の論文
- 2007-03-31
著者
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Inoue Matsuhisa
Kitasato University School Of Medicine
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Inoue Matsuhisa
Kitasato University
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Kaneko Kenichi
Department of Regulation Biochemistry, Kitasato University School of Medicine
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Sato Yoshinori
Department of Environmental Infectious Diseases, Graduate School of Medical Sciences, Kitasato Unive
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Ishihara Kazuhiko
Department of Regulation Biochemistry, Kitasato University School of Medicine
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Kaneko Kenichi
Department Of Regulation Biochemistry Kitasato University School Of Medicine
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Kaneko Kenichi
Department Of Aeronautical Engineering College Of Engineering Univ. Of Osakaprefecture.
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Ishihara Kazuhiko
Department Of Biochemistry Kitasato University Graduate School Of Medical Sciences
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Ishihara Kazuhiko
Department Of Regulation Biochemistry Kitasato University School Of Medicine
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Sato Yoshinori
Department Of Environmental Infectious Diseases Graduate School Of Medical Sciences Kitasato Univers
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Sato Yoshinori
Department Of Bioresource Science Ibaraki University College Of Agriculture
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Inoue Matsuhisa
Kitasato Univ.
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SATO Yoshinori
Department of Bioclimatology and Medicine. Research Institute of Bioregulation. Kyushu University
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