Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0031099 (periodontitis)
 12,489 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The salivary peptide histatin 5 has been reported to be an inhibitor of the Arg- and Lys-specific proteinases of Porphyromonas gingivalis, an oral pathogen associated with periodontitis. In this study a purified P. gingivalis proteinase preparation consisting of a complex of the Arg- and Lys-specific proteinases and adhesins was assayed using chromogenic substrates in the presence of histatin 5. Histatin 5 produced a concentration-dependent decrease in the initial rate of hydrolysis of the chromogenic substrates by both proteinases. However, pre-incubation of histatin 5 with the purified proteinase preparation or a P. gingivalis cell sonicate for 10 min prior to assay with the chromogenic substrates showed that under these conditions the salivary peptide did not decrease the initial rate of chromogen release. Mass spectrometric analysis revealed rapid degradation of histatin 5 at all four lysyl and all three arginyl residues by the P. gingivalis proteinases. This study demonstrates that histatin 5 is a substrate for the P. gingivalis extracellular Arg- and Lys-specific cysteine proteinases and not an inhibitor.
 ...
PMID:Histatin 5 is a substrate and not an inhibitor of the Arg- and Lys-specific proteinases of Porphyromonas gingivalis. 975 56

One of the salient features of periodontitis and gingivitis is the increase in the levels of bacterial and host-derived proteolytic enzymes in oral inflammatory exudates. This study evaluated the potential of histatin 5, a 24-residue histidine-rich salivary antimicrobial protein, to inhibit these enzymes. Using biotinylated gelatin as a substrate, histatin 5 was found to inhibit the activity of the host matrix metalloproteinases MMP-2 and MMP-9 with 50% inhibitory concentrations (IC50s) of 0.57 and 0.25 microM, respectively. To localize the domain responsible for this inhibition, three peptides containing different regions of histatin 5 were synthesized and tested as inhibitors of MMP-9. Peptides comprising residues 1 to 14 and residues 4 to 15 of histatin 5 showed much lower inhibitory activities (IC50, 21.4 and 20.5 microM, respectively), while a peptide comprising residues 9 to 22 showed identical activity to histatin 5 against MMP-9. These results point to a functional domain localized in the C-terminal part of histatin 5. To evaluate the effect of histatin 5 on bacterial proteases, a detailed characterization of histatin 5 inhibition of gingipains from Porphyromonas gingivalis was carried out using purified Arg- and Lys-specific enzymes. Kinetic analysis of the inhibition of the Arg-gingipain revealed that histatin 5 is a competitive inhibitor, affecting only the Km with a K(i) of 15 microM. In contrast, inhibition of Lys-gingipain affected both the Km and Vmax, suggesting that both competitive and noncompetitive competitive processes underlie this inhibition. The inhibitory activity of histatin 5 against host and bacterial proteases at physiological concentrations points to a new potential biological function of histatin in the oral cavity.
 ...
PMID:Salivary histatin 5 is an inhibitor of both host and bacterial enzymes implicated in periodontal disease. 1117 5

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.
 ...
PMID: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. 1140 91

The cell-surface components of Porphyromonas gingivalis have various biological activities. In the present study, we investigated the virulence of several cell-surface components prepared from P. gingivalis in human gingival fibroblasts (HGF). Furthermore the preventive effect of salivary protein histatin 5 was investigated. P. gingivalis polysaccharide (PS) significantly inhibited HGF proliferation, but lipopolysaccharide and outer-membrane protein did not. By using ELISA analysis, DNA fragmentation in HGFs was observed intracellularly when treated with the PS. These results suggest that the PS of P. gingivalis can induce apoptosis in HGF. Pretreatment of PS with histatin 5 restrained the inhibitory effect of PS on HGF proliferation. Histatin 5 also suppressed the apoptotic cell death in HGF induced by PS stimulation. The present study suggests that the PS of P. gingivalis can modulate the cell population in periodontal tissue, causing periodontitis by inducing HGF cell death through apoptosis. Also histatin 5 can inhibit the PS activity and may play an important part in the regulation of inflammatory periodontal diseases.
 ...
PMID:Histatin 5 inhibits apoptosis in human gingival fibroblasts induced by porphyromonas gingivalis cell-surface polysaccharide. 1564 64

Chronic periodontitis is a widespread and major dental disease. Recent studies have analyzed a possible relationship between polymorphism of several genes and periodontitis. Histatins are salivary polypeptides with fungicidal activities against Candida albicans and yeast and bactericidal activities against Porphyromonas gingivalis and Streptococcus mutans. Histatins are part of the innate defense of the oral cavity. We examined the frequency of the polymorphism codon 23 of the histatin 3 gene (HIS2 allele) in relation to periodontitis in the Japanese population. The subjects were 143 Japanese individuals, of which 63 were healthy control subjects and 80 were periodontal patients. We isolated genomic DNA from lingual mucosal cells and tested them for single nucleotide polymorphism (SNP) by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The incidence of polymorphism was analyzed statistically by Fisher's exact test. The results indicated that the gene polymorphism at codon 23 of the histatin 3 gene was not associated with periodontitis in the Japanese population (p = 0.166). Rather, if at all, it appeared to be associated with resistance to periodontitis.
 ...
PMID:Polymorphism of salivary histatin gene and periodontal disease in the Japanese population. 1975