Abstract
In this study, we demonstrate that Porphyromonas gingivalis fimbrillin, a major component of bacterial fimbriae, is one of the fibronectin-binding proteins and that fibronectin is a potent inhibitor of the adherence of the bacteria to host cells and of the pathogenesis of the bacterium that acts by binding to the fimbriae. A Western blotting (immunoblotting) assay showed that fibronectin binds strongly to P. gingivalis fimbrillin. The fimbrial binding to fibronectin was also evidenced by a binding assay involving 125I-labeled fimbriae. Furthermore, fibronectin markedly inhibited the fimbria-induced expression of interleukin-1beta and neutrophil-specific chemoattractant KC genes in macrophages. The inhibitory action depended on the fimbrial interaction with heparin-binding and cell attachment domains in the fibronectin structure. The binding of P.gingivalis to mouse peritoneal macrophages via its fimbriae was inhibited by fibronectin. Fibronectin also inhibited the bacterial cell-induced expression of interleukin-1beta and KC genes in the macrophages. These results demonstrate the importance of fibronectin as a modulator of the pathogenic mechanism of P. gingivalis, a pathogen that causes adult periodontal disease.
MeSH terms
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Adhesins, Bacterial*
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Adult
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Animals
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Bacterial Adhesion / physiology
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Bacterial Outer Membrane Proteins / metabolism*
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Bacterial Proteins / metabolism*
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Binding Sites
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Carrier Proteins*
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Chemokine CXCL1
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Chemokines, CXC*
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Chemotactic Factors / biosynthesis
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Chemotactic Factors / genetics
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Fibronectins / metabolism*
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Fimbriae Proteins*
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Fimbriae, Bacterial / metabolism
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Gene Expression
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Growth Substances / biosynthesis
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Growth Substances / genetics
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Heparin / metabolism
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Humans
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In Vitro Techniques
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Intercellular Signaling Peptides and Proteins*
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Interleukin-1 / biosynthesis
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Interleukin-1 / genetics
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Lipopolysaccharides / metabolism
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Macrophages, Peritoneal / immunology
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Macrophages, Peritoneal / metabolism
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Macrophages, Peritoneal / microbiology
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Mice
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Mice, Inbred BALB C
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Periodontal Diseases / etiology
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Porphyromonas gingivalis / metabolism*
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Porphyromonas gingivalis / pathogenicity*
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Protein Binding
Substances
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Adhesins, Bacterial
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Bacterial Outer Membrane Proteins
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Bacterial Proteins
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CXCL1 protein, human
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Carrier Proteins
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Chemokine CXCL1
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Chemokines, CXC
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Chemotactic Factors
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Cxcl1 protein, mouse
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Fibronectins
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Growth Substances
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Intercellular Signaling Peptides and Proteins
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Interleukin-1
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Lipopolysaccharides
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fibronectin-binding proteins, bacterial
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fimbrillin
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Fimbriae Proteins
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Heparin