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)

Interleukin-1beta (IL-1beta) mediates destruction of matrix collagens in diverse inflammatory diseases including arthritis, periodontitis, and pulmonary fibrosis by activating fibroblasts, cells that interact with matrix proteins through integrin-based adhesions. In vitro, IL-1beta signaling is modulated by focal adhesions, supramolecular protein complexes that are enriched with tyrosine kinases and phosphatases. We assessed the importance of tyrosine phosphatases in regulating cell-matrix interactions and IL-1beta signaling. In human gingival fibroblasts plated on fibronectin, IL-1beta enhanced the maturation of focal adhesions as defined by morphology and enrichment with paxillin and alpha-actinin. IL-1beta also induced activation of ERK and recruitment of phospho-ERK to focal complexes/adhesions. Treatment with the potent tyrosine phosphatase inhibitor pervanadate, in the absence of IL-1beta, recapitulated many of these responses indicating the importance of tyrosine phosphatases. Immunoblotting of collagen bead-associated complexes revealed that the tyrosine phosphatase, SHP-2, was also enriched in focal complexes/adhesions. Depletion of SHP-2 by siRNA or by homologous recombination markedly altered IL-1beta-induced ERK activation and maturation of focal adhesions. IL-1beta-induced tyrosine phosphorylation of SHP-2 on residue Y542 promoted focal adhesion maturation. Association of Gab1 with SHP-2 in focal adhesions correlated temporally with activation of ERK and was abrogated in cells expressing mutant (Y542F) SHP-2. We conclude that IL-1beta mediated maturation of focal adhesions is dependent on tyrosine phosphorylation of SHP-2 at Y542, leading to recruitment of Gab1, a process that may influence the downstream activation of ERK.
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PMID:Tyrosine phosphatase SHP-2 regulates IL-1 signaling in fibroblasts through focal adhesions. 1625 12

Porphyromonas gingivalis is a predominant periodontal pathogen that expresses a number of potential virulence factors involved in the pathogenesis of periodontitis. Gingival epithelial cells are spontaneously exposed to bacterial attacks and function to prevent invasion by bacteria into deeper tissues. P. gingivalis fimbriae are a critical factor for mediation of interaction of the organism with host tissues, as they promote both bacterial adhesion to and invasion of targeted sites. Fimbriae are capable of binding to human salivary components, extracellular matrix proteins, and commensal bacteria, while they also strongly adhere to cellular alpha5beta1-integrin. Following adhesion to alpha5beta1-integrin, P. gingivalis is captured by cellular pseudopodia, which enables invagination through an actin-mediated pathway. The invasive event has been reported to require host cellular dynamin, actin fibers, microtubules, and lipid rafts. Following passage through the epithelial barrier, the intracellular pathogen impairs cellular function. Fimbriae are classified into 6 genotypes (types I to V and Ib) based on the diversity of the fimA genes encoding each fimbria subunit, and intracellular P. gingivalis with type II fimbriae has been found to clearly degrade integrin-related signaling molecules, paxillin, and focal adhesion kinase, which disables cellular migration and proliferation. These events are considered to integrate the bacterial strategy for persistence in periodontal tissues.
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PMID:Disruption of epithelial barrier and impairment of cellular function by Porphyromonas gingivalis. 1748 50

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