<i>Porphyromonas gingivalis</i> inhibits M2 activation of macrophages by suppressing α‐ketoglutarate production in mice

Yu, Shanshan; Ding, Lanlin; Dong, Liang; Luo, Lijun

doi:10.1111/omi.12241

Cited by 29 publications

(30 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, M2, or alternatively activated macrophages, generally associated with wound healing and tissue repair, are also found within periodontal tissues 73,74 . P. gingivalis is associated with M1 polarization and hyperinflammation, 75 but the lipopolysaccharide has been shown to support M2 polarization 74 . T. forsythia supports an M2 phenotype and has been associated with a delayed macrophage response 76,77 .…”

Section: Discussionmentioning

confidence: 99%

Treponema denticola stimulates Oncostatin M cytokine release and de novo synthesis in neutrophils and macrophages

Jones

Vanyo

Ibraheem

et al. 2020

Journal of Leukocyte Biology

View full text Add to dashboard Cite

Oncostatin M (OSM) is a pleiotropic cytokine elevated in a number of inflammatory conditions including periodontal disease. OSM is produced by a variety of immune cells and has diverse functionality such as regulation of metabolic processes, cell differentiation, and the inflammatory response to bacterial pathogens. The oral cavity is under constant immune surveillance including complementary neutrophil and macrophage populations, due to a persistent symbiotic bacterial presence. Periodontal disease is characterized by a dysbiotic bacterial community, with an abundance of Treponema denticola. Despite strong associations with severe periodontal disease, the source and mechanism of the release of OSM have not been defined in the oral cavity. We show that OSM protein is elevated in the gingival epithelium and immune cell infiltrate during periodontal disease. Furthermore, salivary and oral neutrophil OSM is elevated in correlation with the presence of T. denticola. In an air pouch infection model, T. denticola stimulated higher levels of OSM than the oral pathogen Porphorymonas gingivalis, despite differential recruitment of innate immune cells suggesting T. denticola has distinct properties to elevate OSM levels. OSM release and transcription were increased in isolated human blood, oral neutrophils, or macrophages exposed to T. denticola in vitro as measured by ELISA, qPCR, and microscopy. Using transcription, translation, and actin polymerization inhibition, we found that T. denticola stimulates both OSM release through degranulation and de novo synthesis in neutrophils and also OSM release and synthesis in macrophages. Differential induction of OSM by T. denticola may promote clinical periodontal disease.

show abstract

Section: Discussionmentioning

confidence: 99%

Treponema denticola stimulates Oncostatin M cytokine release and de novo synthesis in neutrophils and macrophages

Jones

Vanyo

Ibraheem

et al. 2020

Journal of Leukocyte Biology

View full text Add to dashboard Cite

show abstract

“…All experimental protocols were approved by the Animal Use and Care Committee of Tongji University. Isolation and culture of murine bone marrow‐derived macrophages (BMDMs) are described in our published study 28 . Briefly, 6‐8 week‐old female C57BL/6 mice were sacrificed, and both tibiae and femurs were collected.…”

Section: Methodsmentioning

confidence: 99%

Porphyromonas gingivalis facilitated the foam cell formation via lysosomal integral membrane protein 2 (LIMP2)

Yang

Xia

et al. 2020

J of Periodontal Research

View full text Add to dashboard Cite

Objective The involvement of lysosomal integral membrane protein 2 (LIMP2) in cholesterol transport and formation of foam cells under the infection of Porphyromonas gingivalis (P. gingivalis) is yet to be elucidated. The current study verified the role and explored the mechanism of LIMP2 in promoting foam cell formation by P. gingivalis. Background An association between periodontitis and atherosclerosis (AS) has been established. P. gingivalis is a key pathogen of periodontitis that promotes foam cell formation by regulating activities of CD36 scavenger receptors expressed on the macrophages. LIMP2, a member of CD36 superfamily, is involved in cholesterol efflux. However, whether LIMP2 is involved in the formation of foam cells promoted by P. gingivalis remains unclear. Methods The formation of foam cells was examined by Oil Red O staining. The knockdown of limp2 was identified by qRT‐PCR. The accumulation of cholesterol was monitored by Cholesterol Assay Kit. The location of P. gingivalis was visualized by confocal microscopy. Cathepsin L activity was monitored with Magic Red Cathepsin L Assay Kit. The key genes and pathways in P. gingivalis‐infected macrophages were explored by RNA sequencing. The protein level was investigated by Western blotting. Results Porphyromonas gingivalis increases foam cells formation and upregulates the expression of LIMP2 in foam cells. The knockdown of limp2 decreases the number of foam cells and increases cholesterol export, which is related to lysosomal functions. In addition, the interaction between LIMP2 and caveolin‐1(CAV1) might contribute to this process, and NF‐κB and JNK activity is required for increased expression of P. gingivalis‐induced LIMP2. Conclusions This study suggested that LIMP2 is involved in the foam cells formation facilitated by P. gingivalis, which favors a close connection between periodontitis and atherosclerosis (AS).

show abstract

“…Whether P. gingivalis-LPS has this capacity is not known. P. gingivalis causes an imbalance in M1/ M2 activation in macrophages, resulting in a hyperinflammatory environment that promotes the pathogenesis of periodontitis [78]. These authors reported that P. gingivalis or P. gingivalis-derived LPS-induced inflammatory responses enhanced M1 macrophages and suppressed M2 macrophages, even in the presence of IL-4.…”

Section: Activation By Lipopolysaccharidementioning

confidence: 99%

“…LPS [ 4 , 76 ] P.g . causes imbalance in the M1/M2 phenotype of microglia [ 78 ] Leptomeningeal cells P.g . LPS stimulated transfer of inflammatory signals from peripheral macrophages to brain-resident microglia [ 83 , 84 ] Administration of P.g .…”

Section: Aimmentioning

confidence: 99%

Interaction between genetic factors, Porphyromonas gingivalis and microglia to promote Alzheimer’s disease

Olsen

Singhrao

2020

Journal of Oral Microbiology

View full text Add to dashboard Cite

In late-onset Alzheimer disease (AD) pathogenesis, genes, infections and immunity could be significant factors. We have reviewed if the keystone periodontal pathogen Porphyromonas gingivalis may affect genes and microglia (primary immune cells in the brain) to promote AD development. Genes for apolipoprotein, clusterin, CD33, triggering receptor expressed on myeloid cells-2 (TREM-2), tyrosine kinase binding protein (TYR-OBP), and complement receptors can affect microglia. Most of these genes can also be affected by P. gingivalis via its mastering of immune suppression. Besides, P. gingivalis can affect microglia directly in several ways. Taken together, genetic predisposition, P. gingivalis infection and microglia could promote neurodegeneration typical of that reported for AD.

show abstract

Porphyromonas gingivalis inhibits M2 activation of macrophages by suppressing α‐ketoglutarate production in mice

Cited by 29 publications

References 29 publications

Treponema denticola stimulates Oncostatin M cytokine release and de novo synthesis in neutrophils and macrophages

Treponema denticola stimulates Oncostatin M cytokine release and de novo synthesis in neutrophils and macrophages

Porphyromonas gingivalis facilitated the foam cell formation via lysosomal integral membrane protein 2 (LIMP2)

Interaction between genetic factors, Porphyromonas gingivalis and microglia to promote Alzheimer’s disease

Contact Info

Product

Resources

About