Subversion of Lipopolysaccharide Signaling in Gingival Keratinocytes via MCPIP-1 Degradation as a Novel Pathogenic Strategy of Inflammophilic Pathobionts

Gasiorek, Anna; Dobosz, Ewelina; Potempa, Barbara; Ciaston, Izabela; Wilamowski, Mateusz; Oruba, Zuzanna; Lamont, Richard J.; Jura, Jolanta; Potempa, Jan

doi:10.1128/mbio.00502-21

Cited by 9 publications

(18 citation statements)

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“…Substrate hydrolysis was measured at 405 nm for 40 min, and activity was presented as milli-optical density units per minute per microliter of sample. Before stimulation of eucaryotic cells, enzymes were activated with 10 mM l -cysteine as described recently ( 11 ).…”

Section: Methodsmentioning

confidence: 99%

“…Isolation of OMVs was performed as described previously ( 10 , 11 ). Bacterial suspensions (OD 600 of 1) were sonicated for 90 s in a water bath to increase the release of OMVs from the bacterial surface.…”

Section: Methodsmentioning

confidence: 99%

“…On mucosal surfaces, proteolytically active gingipains target antibacterial peptides, components of the complement system, antibodies, cytokines, and cell surface proteins. The limited proteolysis of protease-activated receptors (PARs) activates proinflammatory responses in platelets, gingival epithelial cells, fibroblasts, neutrophils, and osteoblasts ( 7 – 10 ) Conversely, gingipains taken up by cells efficiently inactivate intracellular key molecules in signaling pathways ( 11 ). Together, this leads to paralysis of the antibacterial cellular and humoral responses of the host.…”

Section: Introductionmentioning

confidence: 99%

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Proteolytic Activity-Independent Activation of the Immune Response by Gingipains from Porphyromonas gingivalis

Ciaston

Budziaszek

Satała

et al. 2022

mBio

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Proteolytic Activity-Independent Activation of the Immune Response by Gingipains from Porphyromonas gingivalis

Ciaston

Budziaszek

Satała

et al. 2022

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“…Monocyte chemoattractant protein‐induced protein‐1 (MCPIP‐1), also called Regnase‐1, is a host inflammatory response cytokine RNase 9 . It was recently demonstrated that P. gingivalis can degrade MCPIP‐1 by its gingipains, which leads to the overactivation of the NF‐κB signaling pathway and increase the transcripts of proinflammatory cytokines 10 . MCPIP‐1 acts as a broad suppressor of miRNA activity and biogenesis 11 .…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, suppression of MALT‐1 increases MCPIP‐1 activity 17 . It was hypothesized that MCPIP‐1 depletion in periodontitis can be an outcome of MALT‐1 activation, however, this was not yet proven 10 . Indeed, simultaneous regulations of MCPIP‐1 and MALT‐1 gene and protein expressions by periodontitis‐associated bacteria and inflammatory mediators have not been elucidated as well.…”

Section: Introductionmentioning

confidence: 99%

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

Firatli

Fıratlı

Loimaranta

et al. 2022

Journal of Periodontology

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Background:The aim of this study was to evaluate oral bacteria-and interleukin (IL)-1β-induced protein and mRNA expression profiles of monocyte chemoattractant protein-1-induced protein (MCPIP)-1 and mucosa-associated lymphoid tissue lymphoma translocation protein (MALT)-1 in human gingival keratinocyte monolayers and organotypic oral mucosal models. Methods: Human gingival keratinocyte (HMK) monolayers were incubated with Porphyromonas gingivalis, Fusobacterium nucleatum, P. gingivalis lipopolysaccharide (LPS) and IL-1β. The protein levels of MCPIP-1 and MALT-1 were examined by immunoblots and mRNA levels by qPCR. MCPIP-1 and MALT-1 protein expression levels were also analyzed immunohistochemically using an organotypic oral mucosal model. One-way analysis of variance followed by Tukey correction was used in statistical analyses. Results: In keratinocyte monolayers, MCPIP-1 protein expression was suppressed by F. nucleatum and MALT-1 protein expression was suppressed by F. nucleatum, P. gingivalis LPS and IL-1β. P. gingivalis seemed to degrade MCPIP-1 and MALT-1 at all tested time points and degradation was inhibited when P. gingivalis was heat-killed. MCPIP-1 mRNA levels were increased by P. gingivalis, F. nucleatum, and IL-1β, however, no changes were observed in MALT-1 mRNA levels. Conclusion: Gingival keratinocyte MCPIP-1 and MALT-1 mRNA and protein expression responses are regulated by infection and inflammatory mediators. These findings suggest that periodontitis-associated bacteria-inducedThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

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Periodontal and microbiological data in patients with mucous membrane pemphigoid in a French population in 2021–2022: A pilot cross‐sectional study

Ejeil,

Gaultier,

Catherine

et al. 2024

Health Science Reports

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Background and AimsIn the case of mucous membrane pemphigoid with gingival expression (gMMP), the complete healing of the gingiva is generally not achieved despite medical treatment. Therefore, patients' oral comfort is impaired. The dysbiotic periodontal microbiota, generated by a lack of oral hygiene associated with persistent gingival pain, could the immunopathological mechanism to persist. The main objective of this study was to characterize the subgingival microbiota of the gMMP patients, and to highlight a potential link between this microbiological data and the clinical data.MethodsSubgingival biofilm was collected from 15 gMMP patients, medically treated or not, but not receiving periodontal treatment. The usual clinical periodontal parameters were recorded. The biofilm was analyzed by polymerase chain reaction quantitative. The risk factors of severe erosive gingivitis and severe periodontitis were assessed using Chi‐square or Fischer's exact test were used.ResultsWhatever the medical and periodontal conditions of the patients, the results showed the existence of three main communities of periodontopathic, dysbiotic bacteria. The first including Tannnerella forsythia, Peptostreptococcus micros, Fusobacterium nucleatum, and Campylobacter rectus, was found in 100% of the patients, the second enriched with Treponema denticola in 60% and the third enriched with Porphyromonas gingivalis and Prevotella intermedia in 26%. Furthermore, there was a significant positive link between the duration of gMMP and the severity of erosive gingivitis (p = 0.009), and the loss of deep periodontal tissue (p = 0.04).ConclusionThis pilot study suggests a high periodontal risk in gMMP patients. The pathological processes, autoimmune on the one hand and plaque‐induced on the other, may amplify each other. The application of periodontal therapy is therefore necessary in parallel with medical treatment. Nevertheless, further controlled studies are required to validate and complement these preliminary results.

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Subversion of Lipopolysaccharide Signaling in Gingival Keratinocytes via MCPIP-1 Degradation as a Novel Pathogenic Strategy of Inflammophilic Pathobionts

Abstract: Periodontitis is a highly prevalent disease caused by accumulation of a bacterial biofilm. Periodontal pathogens use a number of virulence strategies that are under intensive study to find optimal therapeutic approaches against bone loss.

Cited by 9 publications

References 54 publications

Proteolytic Activity-Independent Activation of the Immune Response by Gingipains from Porphyromonas gingivalis

Proteolytic Activity-Independent Activation of the Immune Response by Gingipains from Porphyromonas gingivalis

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

Periodontal and microbiological data in patients with mucous membrane pemphigoid in a French population in 2021–2022: A pilot cross‐sectional study

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