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Infection and Immunity, October 2002, p. 5695-5705, Vol. 70, No. 10
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.10.5695-5705.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

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

Peter L. W. Yun,1* Arthur A. DeCarlo,2 Charles Collyer,3 and Neil Hunter1

Institute of Dental Research, Centre for Oral Health, Westmead Hospital, Wentworthville, Sydney, New South Wales 2145,1 School of Molecular & Microbial BioSciences, University of Sydney, Sydney, New South Wales 2006, Australia,3 NSU Dental, Nova Southeastern University, Fort Lauderdale, Florida2

Received 10 April 2002/ Returned for modification 20 June 2002/ Accepted 22 July 2002

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.


* Corresponding author. Mailing address: Institute of Dental Research, Centre for Oral Health, Westmead Hospital, P.O. Box 533, Wentworthville, Sydney, NSW 2145, Australia. Phone: 61-2-98458764. Fax: 61-2-98457599. E-mail: plwyun{at}yahoo.com.

Editor: E. I. Tuomanen


Infection and Immunity, October 2002, p. 5695-5705, Vol. 70, No. 10
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.10.5695-5705.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.




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