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Subinhibitory concentrations of tetracyclines induce lipopolysaccharide shedding by Porphyromonas gingivalis and modulate the host inflammatory response
Author(s) -
Tanabe S.,
Yoshioka M.,
Hinode D.,
Grenier D.
Publication year - 2014
Publication title -
journal of periodontal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.31
H-Index - 83
eISSN - 1600-0765
pISSN - 0022-3484
DOI - 10.1111/jre.12140
Subject(s) - doxycycline , tetracycline , porphyromonas gingivalis , lipopolysaccharide , microbiology and biotechnology , tumor necrosis factor alpha , secretion , polymyxin b , antibiotics , chemistry , biology , bacteria , immunology , biochemistry , genetics
Background and Objective Antibiotics at below minimal inhibitory concentrations ( MIC s) may induce various biological responses in bacteria. In this study, we hypothesized that subinhibitory concentrations (sub IC s) of tetracycline and doxycycline induce the shedding of lipopolysaccharide ( LPS ) by Porphyromonas gingivalis and, as a consequence, may contribute to enhancing the host inflammatory response associated with periodontitis. Material and Methods A polymyxin‐based enzyme‐linked immunosorbent assay was used to quantify LPS shedding by P. gingivalis grown in the presence of sub IC s of tetracycline and doxycycline. A macrophage model was used to show that tetracycline‐ and doxycycline‐mediated LPS shedding by P . gingivalis can induce cytokine secretion. The secretion of interleukin (IL)‐1β, IL ‐8, and tumor necrosis factor‐α was quantified by enzyme‐linked immunosorbent assay . Results LPS was shed spontaneously in a time‐dependent way by P. gingivalis during growth. LPS shedding was significantly increased by growth in the presence of subICs of tetracycline and doxycycline corresponding to 1/20 of their MICs (0.025 μg/mL for tetracycline and 0.0125 μg/mL for doxycycline). This shedding was not associated with an increased rate of bacterial cell lysis. Stimulating macrophages with a P. gingivalis culture supernatant induced the secretion of IL‐1β, IL‐8 and tumor necrosis factor‐α when the bacteria were grown in the presence of 1/20 MIC of the antibiotics. Conclusion Our study showed that growing P. gingivalis in the presence of sub IC s of either tetracycline or doxycycline induces LPS shedding. Shed LPS may in turn increase cytokine secretion in a macrophage model.