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Interleukin 12 (IL-12) is an efficient inducer and enhancer of gamma interferon (IFN-gamma) production by both resting and activated T cells. There is evidence that human monocytes exposed to IFN-gamma have enhanced ability to produce IL-12 when stimulated with lipopolysaccharide (LPS). In this study, it was demonstrated that LPS from the oral periodontal pathogen Porphyromonas gingivalis stimulated monocytes primed with IFN-gamma to release IL-12, thereby enhancing IFN-gamma accumulation in T-cell populations. P. gingivalis LPS was shown to enhance IL-12 induction of IFN-gamma in T cells in a manner independent from TNF-alpha contribution. The levels of T-cell IL-12 receptors were not affected by P. gingivalis LPS and played only a minor role in the magnitude of the IFN-gamma response. These data suggest that LPS from P. gingivalis establishes an activation loop with IL-12 and IFN-gamma with potential to augment the production of inflammatory cytokines in relation to the immunopathology of periodontitis. We previously reported that the major cysteine proteinases (gingipains) copurifying with LPS in this organism were responsible for reduced IFN-gamma accumulation in the presence of IL-12. However, the addition of the gingipains in the presence of LPS resulted in partial restoration of the IFN-gamma levels. In the destructive periodontitis lesion, release of gingipains from the outer membrane (OM) of P. gingivalis could lead to the downregulation of Th1 responses, while gingipain associated with LPS in the OM or in OM vesicles released from the organism could have net stimulatory effects.

infection and immunity

Modulation of an Interleukin-12 and Gamma Interferon Synergistic Feedback Regulatory Cycle of T-Cell and Monocyte Cocultures by<i>Porphyromonas gingivalis</i>Lipopolysaccharide in the Absence or Presence of Cysteine Proteinases

Modulation of an Interleukin-12 and Gamma Interferon Synergistic Feedback Regulatory Cycle of T-Cell and Monocyte Cocultures byPorphyromonas gingivalisLipopolysaccharide in the Absence or Presence of Cysteine Proteinases