Activation of NLRP3 and AIM2 Inflammasomes by Porphyromonas gingivalis Infection

Park, Eun-Joo; Na, Hee Sam; Song, Yuri; Shin, Seong Yeol; Kim, You-Me; Chung, Jin

doi:10.1128/iai.00862-13

Cited by 178 publications

(222 citation statements)

References 39 publications

Supporting

Mentioning

198

Contrasting

Unclassified

Order By: Relevance

“…2). In fact, among all the genes, IL-1β was the only one that was examined and found to be involved in periodontal tissue destruction in GCF in a previous study (28). In addition, the expression levels of ASC and CASP1 were significantly upregulated in the GCF of patients with gingivitis compared with healthy controls in the present study (Fig.…”

Section: Discussionsupporting

confidence: 64%

Effects of bodybuilding and protein supplements in saliva, gingival crevicular fluid, and serum

et al. 2017

View full text Add to dashboard Cite

, and bleeding on probing (BOP) were recorded. GI and BOP were higher in group BB-G and G than in group H (P < 0.01), but PI, PD, and CAL were similar between groups (P > 0.05). In GCF, CASP1, ASC, and IL-1β expression were upregulated in group G compared with groups BB-G and H (P < 0.01). In addition, ASC (P < 0.05) and IL-1β (P < 0.01) were downregulated in group BB-G compared with group H. CASP1, IL-1β (P < 0.01), and ASC in the saliva were downregulated in group BB-G compared with groups H and G (P < 0.05). CASP1, IL-1β, and ASC may play a role in the pathogenesis of gingivitis. Bodybuilding and supplement usage may decrease gingival inflammation by downregulating CASP1, IL-1β, and ASC.

show abstract

Section: Discussionsupporting

confidence: 64%

Effects of bodybuilding and protein supplements in saliva, gingival crevicular fluid, and serum

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Our current study demonstrates that P. gingivalis fimbriae are able to inhibit IL-1β at the second signal level by interfering with ATP signaling through the purinergic receptor, P2X7. A recent work [46] reported that P. gingivalis activates ATP release and that the inhibition of K + efflux by increasing extracellular K + concentration blocked caspase-1 activation, IL-1β secretion, and pyroptic cell death induced by this pathogen. Here, we showed that this mechanism of IL-1β secretion by P. gingivalis is not only dependent of K + efflux but it also involves the participation of iPLA 2 which is related to fusion of secretory lysosomes with the plasma membrane in the non-classical secretory events induced by eATP stimulation [25].…”

Section: Discussionmentioning

confidence: 99%

<b><i>Porphyromonas gingivalis</i></b> Fimbriae Dampen P2X7-Dependent Interleukin-1β Secretion

et al. 2014

View full text Add to dashboard Cite

Porphyromonas gingivalis is a major contributor to the pathogenesis of periodontitis, an infection-driven inflammatory disease that leads to bone destruction. This pathogen stimulates pro-interleukin (IL)-1β synthesis but not mature IL-1β secretion, unless the P2X7 receptor is activated by extracellular ATP (eATP). Here, we investigated the role of P. gingivalis fimbriae in eATP-induced IL-1β release. Bone marrow-derived macrophages (BMDMs) from wild-type (WT) or P2X7-deficient mice were infected with P. gingivalis (381) or isogenic fimbria-deficient (DPG3) strain with or without subsequent eATP stimulation. DPG3 induced higher IL-1β secretion after eATP stimulation compared to 381 in WT BMDMs, but not in P2X7-deficient cells. This mechanism was dependent on K⁺ efflux and Ca²⁺-independent phospholipase A₂ activity. Accordingly, non-fimbriated P. gingivalis failed to inhibit apoptosis via the eATP/P2X7 pathway. Furthermore, P. gingivalis-driven stimulation of IL-1β was Toll-like receptor 2 and MyD88 dependent, and not associated with fimbria expression. Fimbria-dependent down-modulation of IL-1β was selective, as levels of other cytokines remained unaffected by P2X7 deficiency. Confocal microscopy demonstrated the presence of discrete P2X7 expression in the absence of P. gingivalis stimulation, which was enhanced by 381-stimulated cells. Notably, DPG3-infected macrophages revealed a distinct pattern of P2X7 receptor expression with a marked focus formation. Collectively, these data demonstrate that eATP-induced IL-1β secretion is impaired by P. gingivalis fimbriae in a P2X7-dependent manner.

show abstract

“…These results suggest a key role for this receptor in the elimination process. Previous studies have shown the ability of infecting pathogens to cause ATP release in a physiological form (22,23). Thus, we measured the ATP release during infection with L. amazonensis at different time points.…”

Section: P2x7 Receptor Is Involved In L Amazonensis Elimination Medimentioning

confidence: 99%

Leukotriene B4 Modulates P2X7 Receptor–MediatedLeishmania amazonensisElimination in Murine Macrophages

Chaves

Marques-da-Silva

Monteiro

et al. 2014

The Journal of Immunology

View full text Add to dashboard Cite

ATP is an important signaling molecule in the immune system, and it is able to bind the P2X7 purinergic receptor. Recently, our group showed that ATP-treated macrophages eliminate Leishmania amazonensis. It has been reported that leukotriene B4 (LTB4) reduces the parasitic load of infected macrophages. Additionally, it has been demonstrated that the P2X7 receptor can induce PLA2 activation and arachidonic acid mobilization. Based on these findings, we investigated whether LTB4 is produced upon P2X7 receptor activation and examined whether LTB4 modulates parasite elimination. Using macrophages lacking the P2X7 receptor, we observed that ATP was not able to reduce L. amazonensis load. This result suggests a role of the P2X7 purinergic receptor in parasite elimination. In addition, ATP was sufficient to induce LTB4 release from infected control macrophages but not from macrophages lacking the P2X7 receptor. Moreover, we found that ATP failed to decrease the parasitic load in 5-lipoxygenase (LO)–deficient macrophages. Treatment with the 5-LO inhibitor AA861 also impairs the ATP effect on parasitic loads. Furthermore, macrophages from 5-LO knockout mice eliminated L. amazonensis in the presence of exogenous LTB4, and macrophages obtained from P2X7 receptor knockout mice eliminated L. amazonensis when incubated with ionomycin. Finally, we demonstrated that in the presence of CP105696, an antagonist for LTB4 high-affinity receptor, ATP was not able to reduce parasitic load. These results indicate that P2X7 receptor activation leads to LTB4 formation, which is required for L. amazonensis elimination.

show abstract

Activation of NLRP3 and AIM2 Inflammasomes by Porphyromonas gingivalis Infection

Cited by 178 publications

References 39 publications

Effects of bodybuilding and protein supplements in saliva, gingival crevicular fluid, and serum

Effects of bodybuilding and protein supplements in saliva, gingival crevicular fluid, and serum

<b><i>Porphyromonas gingivalis</i></b> Fimbriae Dampen P2X7-Dependent Interleukin-1β Secretion

Leukotriene B4 Modulates P2X7 Receptor–MediatedLeishmania amazonensisElimination in Murine Macrophages

Contact Info

Product

Resources

About