&lt;b&gt;&lt;i&gt;Porphyromonas gingivalis&lt;/i&gt;&lt;/b&gt; Fimbriae Dampen P2X7-Dependent Interleukin-1β Secretion

Morandini, Ana Carolina; Ramos-Junior, Erivan Schnaider; Potempa, Jan; Nguyen, Ky-Anh; Oliveira, Ana Carolina; Ojcius, David M.; Scharfstein, Júlio; Coutinho‐Silva, Robson

doi:10.1159/000363338

Cited by 35 publications

(48 citation statements)

References 51 publications

(62 reference statements)

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“…In a previous study, we demonstrated that eATP stimulates IL-1β secretion in P. gingivalis-infected BMDMs, which is dampened by its fimbriae (Morandini et al 2014). To gain further insights into the role of NLRP3 inflammasome regarding P. gingivalis fimbriae induction of IL-1β secretion, we used BMDM derived from wild-type C57BL/6 (WT) and NLRP3 knockout (NLRP3 -/-) mice for comparative analyses of IL-1β processing and release.…”

Section: Nlrp3 Is Necessary For Eatp-induced Il-1β Secretion and Caspmentioning

confidence: 91%

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A Dual Role for P2X7 Receptor during Porphyromonas gingivalis Infection

et al. 2015

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Emerging evidence suggests a role for purinergic signaling in the activation of multiprotein intracellular complexes called inflammasomes, which control the release of potent inflammatory cytokines, such as interleukin (IL) -1β and -18. Porphyromonas gingivalis is intimately associated with periodontitis and is currently considered one of the pathogens that can subvert the immune system by limiting the activation of the NLRP3 inflammasome. We recently showed that P. gingivalis can dampen eATP-induced IL-1β secretion by means of its fimbriae in a purinergic P2X7 receptor-dependent manner. Here, we further explore the role of this purinergic receptor during eATP-induced IL-1β processing and secretion by P. gingivalis-infected macrophages. We found that NLRP3 was necessary for eATP-induced IL-1β secretion as well as for caspase 1 activation irrespective of P. gingivalis fimbriae. Additionally, although the secretion of IL-1β from P. gingivalis-infected macrophages was dependent on NLRP3, its adaptor protein ASC, or caspase 1, the cleavage of intracellular pro-IL-1β to the mature form was found to occur independently of NLRP3, its adaptor protein ASC, or caspase 1. Our in vitro findings revealed that P2X7 receptor has a dual role, being critical not only for eATP-induced IL-1β secretion but also for intracellular pro-IL-1β processing. These results were relevant in vivo since P2X7 receptor expression was upregulated in a P. gingivalis oral infection model, and reduced IFN-γ and IL-17 were detected in draining lymph node cells from P2rx7(-/-) mice. Furthermore, we demonstrated that P2X7 receptor and NLRP3 transcription were modulated in human chronic periodontitis. Overall, we conclude that the P2X7 receptor has a role in periodontal immunopathogenesis and suggest that targeting of the P2X7/NLRP3 pathway should be considered in future therapeutic interventions in periodontitis.

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Section: Nlrp3 Is Necessary For Eatp-induced Il-1β Secretion and Caspmentioning

confidence: 91%

“…Macrophages were derived from bone marrow of WT (C57BL/6), NLRP3 -/-, ASC -/-, Casp1 -/-, and P2X7 -/-mice as previously described (Morandini et al 2014). Detailed information of P. gingivalis infection and subsequent experiments are provided in the Appendix.…”

Section: Bone Marrow-derived Macrophages and P Gingivalis Infectionmentioning

confidence: 99%

A Dual Role for P2X7 Receptor during Porphyromonas gingivalis Infection

et al. 2015

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“…Porphyromonas gingivalis is a Gram-negative anaerobic bacterium that is considered a keystone pathogen (4). It produces several virulence factors such as lipopolysaccharide (LPS) and fimbriae in order to activate macrophages (5,6) and invade different cell types, such as endothelial (7) and epithelial cells (8,9). Several mechanisms, such as modulation of gene and protein expression, are used by P. gingivalis to compromise immune function at the periodontal level (1,3).…”

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confidence: 99%

Identification and Characterization of MicroRNA Differentially Expressed in Macrophages Exposed to Porphyromonas gingivalis Infection

et al. 2017

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MicroRNAs (miRNAs) are short, noncoding RNAs involved in the regulation of several processes associated with inflammatory diseases and infection. Bacterial infection modulates miRNA expression to subvert any innate immune response. In this study we analyzed, using microarray analysis, the bacterial modulation of miRNAs in bone marrow-derived macrophages (BMMs) in which activity was induced by infection with Porphyromonas gingivalis. The expression of several miRNAs was modulated 3 h postinfection (at a multiplicity of infection of 25). A bioinformatic analysis was performed to further identify pathways related to the innate immune host response under the influence of selected miRNAs. To assess the effects of the miRNAs identified on cytokine secretion (tumor necrosis factor alpha [TNF-␣] and interleukin-10 [IL-10]), BMMs were transfected with selected miRNA mimics and inhibitors. Transfection with mmu-miR-155 and mmumiR-2137 did not modify TNF-␣ secretion, while their inhibitors increased it. Inhibitors of mmu-miR-2137 and mmu-miR-7674 increased the secretion of the anti-inflammatory factor IL-10. In P. gingivalis-infected BMMs, mmu-miR-155-5p significantly decreased TNF-␣ secretion while inhibitor of mmu-miR-2137 increased IL-10 secretion. In vivo, in a mouse model of P. gingivalis-induced calvarial bone resorption, injection of mmu-miR-155-5p or anti-mmu-miR-2137 reduced the size of the lesion significantly. Furthermore, anti-mmu-miR-2137 significantly reduced inflammatory cell infiltration, osteoclast activity, and bone loss. Bioinformatic analysis demonstrated that pathways related to cytokine-and chemokinerelated pathways but also osteoclast differentiation may be involved in the effects observed. This study contributes further to our understanding of P. gingivalis-induced modulation of miRNAs and their physiological effects. It highlights the potential therapeutic merits of targeting mmu-miR-155-5p and mmumiR-2137 to control inflammation induced by P. gingivalis infection.

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“…It is likely that osteotropic cytokines released from fibroblasts are of additional importance in the pathogenesis of inflammation‐induced bone resorption 17 . It is known that IL‐1β is a key mediator in host immune response against infection as it plays a large role in initiation and maintenance of inflammatory response elicited by pathogens such as Porphyromonas gingivalis 18 . Similarly, IL‐6 is a pleiotropic cytokine with humoral and cellular immune effects related to inflammation, host defense, and tissue injury 19 .…”

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confidence: 99%