Porphyromonas gingivalis gingipain-R enhances interleukin-8 but decreases gamma interferon-inducible protein 10 production by human gingival fibroblasts in response to T-cell contact.
Proteases produced by Porphyromonas gingivalis, an oral pathogen, are considered important virulence factors and may affect the responses of cells equipped with proteinase-activated receptors. The aim of this study was to investigate the effect of the arginine-specific cysteine protease gingipain-R produced by P. gingivalis on chemokine production by human gingival fibroblasts (HGF) and the effect of gingipain-R treatment on the subsequent contact-dependent activation of HGF by T cells. HGF incubated in the presence of purified 47-kDa gingipain-R showed increased levels of interleukin-8 (IL-8) mRNA. Cyclooxygenase-2 (COX-2) mRNA was also induced. Further exposure of HGF to activated T cells resulted in the dose- and time-dependent enhancement of IL-8 transcription and release. T-cell membrane-bound tumor necrosis factor (TNF) was the ligand inducing IL-8 production by HGF, since TNF neutralization abrogated HGF responses to T-cell contact. The enhanced IL-8 release was due, at least in part, to prostaglandin-E(2) production, which was mostly blocked by indomethacin. Gingipain-R proteolytic activity was required since heat inactivation, specific synthetic protease inhibitors, and the natural substrate competitor histatin 5 abrogated its effects. The enhanced production of IL-8 in response to T-cell contact was specific since monocyte chemotactic protein-1 (MCP-1) production was unaffected while interferon-gamma-inducible protein-10 (IP-10) was inhibited. The sum of these activities may result in the recruitment of differential cell types to sites of inflammation since IL-8 preferentially recruits neutrophils and IP-10 attracts activated T cells and may be relevant to the pathogenesis of periodontitis.
Oido-Mori
M
M
Department of Preventive Dentistry, School of Dental Medicine, University of Geneva, 1211 Geneva 14, Switzerland.
Rezzonico
R
R
Wang
P L
PL
Kowashi
Y
Y
Dayer
J M
JM
Baehni
P C
PC
Chizzolini
C
C
D018829:Adhesins, Bacterial; D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000276:immunology; D002478:Cells, Cultured; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000096:biosynthesis* / Q000235:genetics; D003546:Cysteine Endopeptidases / Q000276:immunology*; D015232:Dinoprostone / Q000276:immunology; D005347:Fibroblasts / Q000166:cytology / Q000276:immunology; D000080867:Gingipain Cysteine Endopeptidases; D005881:Gingiva / Q000166:cytology / Q000276:immunology*; D006388:Hemagglutinins / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology*; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D008969:Molecular Sequence Data; D016966:Porphyromonas gingivalis / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D018829:Adhesins, Bacterial; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D000080867:Gingipain Cysteine Endopeptidases; D006388:Hemagglutinins; D016209:Interleukin-8; D007371:Interferon-gamma; D003546:Cysteine Endopeptidases; D015232:Dinoprostone