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Infection and Immunity, September 2001, p. 5650-5660, Vol. 69, No. 9
Institute of Dental Research, University of
New South Wales, Randwick, New South Wales
2052,1 and Department of Biochemistry,
University of Sydney, New South Wales 2006,3
Australia, and Departments of Periodontics and Oral
Biology, University of Alabama at Birmingham, Birmingham, Alabama
352942
Received 2 March 2001/Returned for modification 19 April
2001/Accepted 7 June 2001
Porphyromonas gingivalis cysteine proteinases
(gingipains) have been associated with virulence in destructive
periodontitis, a disease process variously considered to represent an
unregulated stimulation of either T helper type 1 (Th1)- or Th2-type
cells. Critical in maintaining Th1 activity is the response of T
lymphocytes to environmental interleukin 12 (IL-12) in the form of
up-regulation of gamma interferon (IFN-
0019-9567/01/$04.00+0 DOI: 10.1128/IAI.69.9.5650-5660.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Hydrolysis of Interleukin-12 by Porphyromonas
gingivalis Major Cysteine Proteinases May Affect Local Gamma
Interferon Accumulation and the Th1 or Th2 T-Cell Phenotype
in Periodontitis
) production. Here we
demonstrate that in the presence or absence of serum, gingipains were
able to hydrolyze IL-12 and reduce the IL-12-induced IFN-
production
from CD4+ T cells. However, the induction of IL-12
receptors on T cells by gingipains did not correlate with the
enhancement of IFN-
production. The gingipains cleaved IL-12 within
the COOH-terminal region of the p40 and p35 subunit chains, which leads
to IL-12 inactivity, whereas IL-2 in these assays was not affected.
Inactivation of IL-12 by the gingipains could disrupt the cytokine
balance or favor Th2 activities in the progression of periodontitis.
*
Corresponding author. Mailing address: Institute of
Dental Research, C/- University of NSW, Building R2, 22-32 King St.,
Randwick, NSW 2052, Australia. Phone: 61-2-93989610. Fax:
61-2-93850247. E-mail: plwyun{at}yahoo.com.
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