Are <i>Porphyromonas gingivalis</i> Outer Membrane Vesicles Microbullets for Sporadic Alzheimer’s Disease Manifestation?

Singhrao, Simarjit Kaur; Olsen, Ingar

doi:10.3233/adr-180080

Cited by 65 publications

(42 citation statements)

References 84 publications

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“…P. gingivalis LPS promotes M1 macrophage polarization. But current researches indicate that gingipains, pili, and capsule all involve in chronic PD [ 31 , 39 ]. P. gingivalis as anaerobic bacteria lives in the gingival crevicular fluid that directly contacts oxygen.…”

Section: Discussionmentioning

confidence: 99%

Coniferyl Aldehyde Inhibits the Inflammatory Effects of Leptomeningeal Cells by Suppressing the JAK2 Signaling

Wang

Gao

et al. 2020

BioMed Research International

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Background. The brain is in many ways an immunologically and pharmacologically privileged site because of the blood-brain barrier (BBB). But for chronic peripheral inflammation, inflammatory signals can be transmitted from the peripheral system into the central nervous system (CNS) through multiple channels and result in neuroinflammation. Leptomeningeal cells that form the BBB can trigger one signaling pathway by releasing cytokines to transmit inflammatory signals. Besides, the Janus kinase (JAK) family may have a certain function in the activation of leptomeninges. In the present study, we try to use coniferyl aldehyde (CA), a natural anti-inflammatory phenolic compound, to inhibit this inflammatory process and elucidate the underlying molecular mechanisms. Results. Secretion of proinflammatory cytokines (TNF-α, IL-1β, and IL-6) significantly increased after incubation with P. gingivalis. Moreover, TNF-α, IL-1β, and IL-6 levels were upregulated, and the JAK2 signaling was enhanced in leptomeningeal cells in a conditioned medium from activated macrophages, which leads to the immune response in microglia. However, this inflammatory effect of leptomeningeal cells was reversed by CA administration, accompanied by the decreased immune response in microglia. The western blot assay revealed that JAK2 phosphorylation was suppressed in leptomeningeal cells treated with CA. Conclusions. This study demonstrates that activated macrophages by P. gingivalis markedly induce the release of proinflammatory cytokines (TNF-α, IL-1β, and IL-6) from leptomeningeal cells, thereby activating the JAK2 signaling pathway and subsequently enhancing immune responses in microglia in the CNS. CA effectively inhibits the inflammatory effect of leptomeningeal cells via suppressing the JAK2 signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Coniferyl Aldehyde Inhibits the Inflammatory Effects of Leptomeningeal Cells by Suppressing the JAK2 Signaling

Wang

Gao

et al. 2020

BioMed Research International

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“…Outer membrane vesicles (OMVs) are secreted by bacteria, range from 20 to 250 nm in diameter, and carry bacterial lipopolysaccharide (LPS), protease, membrane receptor, DNA, RNA and so forth (Bonnington & Kuehn, 2014;Guerrero-Mandujano, Hernandez-Cortez, Ibarra, & Castro-Escarpulli, 2017;Jan, 2017). Several studies suggested that OMVs play a vital role in the communication and regulation of the host (Maerz et al, 2018;Rosenthal et al, 2014;Sinha et al, 2015) and even indicated that OMVs are related to AD (Aguayo, Schuh, Vicente, & Aguayo, 2018;Olsen, Taubman, & Singhrao, 2016;Singhrao & Olsen, 2018).…”

mentioning

confidence: 99%

Outer membrane vesicles enhance tau phosphorylation and contribute to cognitive impairment

Wei

Peng

Mai

et al. 2019

Journal Cellular Physiology

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Outer membrane vesicles (OMVs) are nanosized vesicles produced by the gut microbiota (GM). The GM is well-known to be involved in the pathological process of Alzheimer's disease (AD). However, the mechanism of OMVs is not clear. In the present study, we demonstrated the involvement of OMVs in the development of cognitive (learning and memory) dysfunction induced by blood-brain barrier (BBB) disruption. More important, further study showed that OMVs induced tau phosphorylation by activating glycogen synthase kinase 3β (GSK-3β) in the hippocampus. OMVs activated astrocytes and microglia, increased secretion of inflammatory cytokines (nuclear factor κB, interleukin-1β, and tumour necrosis factor-α) in the hippocampus. Therefore, OMVs increase the permeability of the BBB and promote the activation of astrocytes and microglia, inducing an inflammatory response and tau hyperphosphorylation by activating the GSK-3β pathway and finally leading to cognitive impairment. K E Y W O R D SAlzheimer's disease, astrocytes, blood-brain barrier, glycogen synthase kinase 3β, gut microbiota, inflammatory cytokines, interleukin-1β, microglia, nuclear factor κB, outer membrane vesicles, tau, tumour necrosis factor-α

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“…P. gingivalis -LPS is released after the lysis of bacteria or as free vesicles outward from the outer membranes of living bacteria. These LPS-containing microvesicles, which function like “microbullets” that land on the host, further perpetuate the invasiveness of P. gingivalis , giving it the ability to destroy periodontal tissues and trigger inflammation (Zhang et al, 2015; Singhrao and Olsen, 2018). The basic chemical composition of P. gingivalis -LPS is nearly identical to that of a typical bacterial endotoxin.…”

Section: Effect Of Lps On P Gingivalis Virulencementioning

confidence: 99%

Pathogenesis of Important Virulence Factors of Porphyromonas gingivalis via Toll-Like Receptors

Liang

Han

et al. 2019

Front. Cell. Infect. Microbiol.

186

131

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Periodontitis is a common intraoral infection and is inextricably linked to systemic diseases. Recently, the regulation between host immunologic response and periodontal pathogens has become a hotspot to explain the mechanism of periodontitis and related systemic diseases. Since Porphyromonas gingivalis ( P. gingivalis ) was proved as critical periodontal pathogen above all, researches focusing on the mechanism of its virulence factors have received extensive attention. Studies have shown that in the development of periodontitis, in addition to the direct release of virulent factors by periodontal pathogens to destroy periodontal tissues, over-low or over-high intrinsic immune and inflammatory response mediated by Toll-like receptors (TLRs) can lead to more lasting destruction of periodontal tissues. It is very necessary to sort out how various cytopathic factors of P. gingivalis mediate inflammation and immune responses between the host through TLRs so as to help precisely prevent, diagnose, and treat periodontitis in clinic. This review summarizes the role of three most widely studied pathogenic factors produced by P. gingivalis (lipopolysaccharide, gingipains, pili) and their interactions with TLRs at the cellular and molecular level in the progress of periodontitis.

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Are Porphyromonas gingivalis Outer Membrane Vesicles Microbullets for Sporadic Alzheimer’s Disease Manifestation?

Cited by 65 publications

References 84 publications

Coniferyl Aldehyde Inhibits the Inflammatory Effects of Leptomeningeal Cells by Suppressing the JAK2 Signaling

Coniferyl Aldehyde Inhibits the Inflammatory Effects of Leptomeningeal Cells by Suppressing the JAK2 Signaling

Outer membrane vesicles enhance tau phosphorylation and contribute to cognitive impairment

Pathogenesis of Important Virulence Factors of Porphyromonas gingivalis via Toll-Like Receptors

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