ArticleMicrobiology (Reading, England)2009
Cleavage of protease-activated receptors on an immortalized oral epithelial cell line by Porphyromonas gingivalis gingipains.
Article in Microbiology (Reading, England), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 55 citations in OpenAlex.
- Role of Cytokines in Bone Diseases and Their Therapeutic Application.ImmunoTargets and therapy · 2026Review
- Immunomodulatory effects of eubiotic and dysbiotic multi-species biofilms on oral keratinocytes.BMC oral health · 2025Article
- Roles of intralesional bacteria in the initiation and progression of oral squamous cell carcinoma.Cancer medicine · 2024Review
- Regulation of gingival keratinocyte monocyte chemoattractant protein-1-induced protein (MCPIP)-1 and mucosa-associated lymphoid tissue lymphoma translocation protein (MALT)-1 expressions by periodontal bacteria, lipopolysaccharide, and interleukin-1β.Journal of periodontology · 2023Article
- Uptake of Nanotitania by Gingival Epithelial Cells Promotes Inflammatory Response and Is Accelerated byInternational journal of molecular sciences · 2021Article
- Ca mobilization and signaling pathways induced by rRgpB in human gingival fibroblast.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2021Article
- Cytokines and Chemokines in Periodontitis.European journal of dentistry · 2020Article
- Triggering NETosis via protease-activated receptor (PAR)-2 signaling as a mechanism of hijacking neutrophils function for pathogen benefits.PLoS pathogens · 2019Article
- Protease-Activated Receptors in the Intestine: Focus on Inflammation and Cancer.Frontiers in endocrinology · 2019Review
- Infection of microglia with Porphyromonas gingivalis promotes cell migration and an inflammatory response through the gingipain-mediated activation of protease-activated receptor-2 in mice.Scientific reports · 2017Article
- Porphyromonas gingivalis gingipains cause defective macrophage migration towards apoptotic cells and inhibit phagocytosis of primary apoptotic neutrophils.Cell death & disease · 2017Article
- The Role of Proteinase-Activated Receptors 1 and 2 in the Regulation of Periodontal Tissue Metabolism and Disease.Journal of immunology research · 2017Review
- Structural Insights into the PorK and PorN Components of the Porphyromonas gingivalis Type IX Secretion System.PLoS pathogens · 2016Article
- Autonomous immunity in mucosal epithelial cells: fortifying the barrier against infection.Microbes and infection · 2016Review
- Porphyromonas gingivalis Gingipain-Dependently Enhances IL-33 Production in Human Gingival Epithelial Cells.PloS one · 2016Article
- Inhibitors of bacterial protease enzymes for periodontal therapy.Clinical and experimental dental research · 2015Article
- Enterococcus faecalis Gelatinase Mediates Intestinal Permeability via Protease-Activated Receptor 2.Infection and immunity · 2015Article
- Gingipains from Porphyromonas gingivalis play a significant role in induction and regulation of CXCL8 in THP-1 cells.BMC microbiology · 2014Article
- Evaluation on potential contributions of protease activated receptors related mediators in allergic inflammation.Mediators of inflammation · 2014Review
- Periodontal treatment downregulates protease-activated receptor 2 in human gingival crevicular fluid cells.Infection and immunity · 2013Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Porphyromonas gingivalis activates protease-activated receptors (PARs) on oral keratinocytes, resulting in downstream signalling for an innate immune response. Activation depends on P. gingivalis gingipains, but could be confounded by lipopolysaccharide signalling through Toll-like receptors. We therefore hypothesized that P. gingivalis cleaves oral keratinocyte PARs in an Arg- (Rgp) or Lys- (Kgp) gingipain-specific manner to upregulate pro-inflammatory cytokines. Immortalized human oral keratinocytes (TERT-2) were incubated with wild-type P. gingivalis (ATCC 33277) or strains from a panel of isogenic gingipain deletion mutants: Kgp-deficient (KDP 129); Rgp-deficient (KDP 133); or Kgp- and Rgp-deficient (KDP 136). After incubation with P. gingivalis, keratinocytes were probed with specific antibodies against the N-terminus of PAR-1 and PAR-2. Using flow cytometry and immunofluorescence, receptor cleavage was marked by loss of specific antibody binding to the respective PARs. TERT-2 cells constitutively expressed high levels of PAR-1 and PAR-2, and lower levels of PAR-3. P. gingivalis ATCC 33277 cleaved PAR-1 and PAR-2 in a dose-dependent manner, while the receptors were unaffected by the protease-negative double mutant (KDP 136) at all m.o.i. tested. The single Kgp-negative mutant preferentially cleaved PAR-1, whereas the Rgp-negative mutant cleaved PAR-2. Wild-type or Kgp-negative mutant cleavage of PAR-1 upregulated expression of IL-1alpha, IL-1beta, IL-6 and TNF-alpha; the Rgp-negative mutant did not modulate these cytokines. Selective cleavage of PAR-1 on oral epithelial cells by P. gingivalis Rgp therefore upregulates expression of pro-inflammatory cytokines.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.