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

Bacteriological and cytological analysis of the saliva, dental plaques, and gingival fluid was carried out in 48 patients with periodontitis and 25 donors. The concentrations of proinflammatory cytokines IL-1 and TNF-alpha were increased, the levels of anti-inflammatory cytokines IL-4 and TFR beta-1 were decreased, and MIF production was suppressed in the patients in comparison with donors. Important theoretical and practical recommendations are offered.
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PMID:[A comprehensive study of the mechanisms of the development of chronic inflammation in periodontitis]. 1096 Nov 5

Porphyromonas gingivalis, a periodontal pathogen, secretes outer membrane vesicles (MVs) that contain major virulence factors, including proteases termed gingipains (Arg-gingipain [Rgp] and Lys-gingipain [Kgp]). We recently showed that P. gingivalis MVs swiftly enter host epithelial cells via an endocytosis pathway and are finally sorted to lytic compartments. However, it remains unknown whether MV entry impairs cellular function. Herein, we analyzed cellular functional impairment following entry of P. gingivalis into epithelial cells, including HeLa and immortalized human gingival epithelial (IHGE) cells. After being taken up by endocytic vacuoles, MVs degraded the cellular transferrin receptor (TfR) and integrin-related signaling molecules, such as paxillin and focal adhesion kinase (FAK), which resulted in depletion of intracellular transferrin and inhibition of cellular migration. Few Rgp-null MVs entered the cells, and these negligibly degraded TfR, whereas paxillin and FAK degradation was significant. In contrast, Kgp-null MVs clearly entered the cells and degraded TfR, while they scarcely degraded paxillin and FAK. In addition, both wild-type and Kgp-null MVs significantly impaired cellular migration, whereas the effect of Rgp-null MVs was limited. Our findings suggest that, following entry of P. gingivalis MVs into host cells, MV-associated gingipains degrade cellular functional molecules such as TfR and paxillin/FAK, resulting in cellular impairment, indicating that P. gingivalis MVs are potent vehicles for transmission of virulence factors into host cells and are involved in the etiology of periodontitis.
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PMID:Entry of Porphyromonas gingivalis outer membrane vesicles into epithelial cells causes cellular functional impairment. 1973 99

Porphyromonas gingivalis, the main etiologic agent of periodontitis, secretes cysteine proteases named gingipains. HRgpA and RgpB gingipains have Arg-specificity, while Kgp gingipain is Lys-specific. Together they can cleave an array of proteins and importantly contribute to the development of periodontitis. In this study we focused on gingipain-exerted proteolysis at the cell surface of human gingival epithelial cells [telomerase immortalized gingival keratinocytes (TIGK)] in order to better understand the molecular mechanisms behind tissue destruction in periodontitis. Using mass spectrometry, we investigated the whole sheddome/degradome of TIGK cell surface proteins by P. gingivalis strains differing in gingipain expression and by purified gingipains, and performed the first global proteomic analysis of gignpain proteolysis at the membrane. Incubation of TIGK cells with P. gingivalis resulted in massive degradation of proteins already at low multiplicity of infection, whereas incubating cells with purified gingipains resulted in more discrete patterns, indicative of a combination of complete degradation and shedding of membrane proteins. Most of the identified gingipain substrates were molecules involved in adhesion, suggesting that gingipains may cause tissue damage through cleavage of cell contacts, resulting in cell detachment and rounding, and consequently leading to anoikis. However, HRgpA and RgpB gingipains differ in their mechanism of action. While RgpB rapidly degraded the proteins, HRgpA exhibited a much slower proteolysis indicative of ectodomain shedding, as demonstrated for the transferrin receptor protein 1 (TFRC). These results reveal a molecular underpinning to P. gingivalis-induced tissue destruction and enhance our knowledge of the role of P. gingivalis proteases in the pathobiology of periodontitis. Proteomics data are available via ProteomeXchange with identifier PXD015679.
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PMID:Proteolysis of Gingival Keratinocyte Cell Surface Proteins by Gingipains Secreted From Porphyromonas gingivalis - Proteomic Insights Into Mechanisms Behind Tissue Damage in the Diseased Gingiva. 3241 Nov 4