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.
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-gamma) 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-gamma 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-gamma 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.
Yun
P L
PL
Institute of Dental Research, University of New South Wales, Randwick, New South Wales 2052, Australia. plwyun@yahoo.com
Decarlo
A A
AA
Collyer
C
C
Hunter
N
N
D018829:Adhesins, Bacterial; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D000080867:Gingipain Cysteine Endopeptidases; D006388:Hemagglutinins / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism*; D008213:Lymphocyte Activation; D010518:Periodontitis / Q000276:immunology* / Q000382:microbiology; D016966:Porphyromonas gingivalis / Q000201:enzymology* / Q000472:pathogenicity*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D018829:Adhesins, Bacterial; D000080867:Gingipain Cysteine Endopeptidases; D006388:Hemagglutinins; D018664:Interleukin-12; D007371:Interferon-gamma; D003546:Cysteine Endopeptidases