Differential inflammasome activation by Porphyromonas gingivalis and cholesterol crystals in human macrophages and coronary artery endothelial cells.
Atherosclerosis
; 235(1): 38-44, 2014 Jul.
Article
em En
| MEDLINE
| ID: mdl-24814648
ABSTRACT
OBJECTIVE:
Observational evidence suggests association between periodontitis and atherosclerotic vascular disease (ASVD), however the cause-effect remains unclear. In this study, we investigated the mechanistic link of the two diseases by measuring production of interleukin (IL)-1ß, a potent inflammatory cytokine, induced via inflammasome activation by a key periodontal pathogen--Porphyromonas gingivalis LPS and cholesterol crystals (CC).METHODS:
An in vitro model of primary human monocyte-derived macrophages (M1 and M2 macrophages) and coronary artery endothelial cells (HCAEC) was employed as a source of inflammasome product-IL-1ß. Both cell types are essential in initial inflammatory process of ASVD. As inflammasome activation requires 2 signals, P. gingivalis LPS was used as a signal1 and CC as a signal2.RESULTS:
We found markedly release of IL-1ß from P. gingivalis LPS-primed M1 and M2 macrophages treated with CC. Unlike macrophages, HCAEC showed no release of IL-1ß in response to P. gingivalis LPS priming and subsequent treatment with either CC or extracellular danger molecule adenosine-5'-triphosphate (signal2). However, HCAEC, which were primed with pro-inflammatory cytokine TNF-α (signal1) and treated with adenosine-5'-triphosphate, consistently secreted minimal IL-1ß. The amount of IL-1ß released from activated HCAEC was much lower than that from M1 or M2 macrophages.CONCLUSIONS:
P. gingivalis LPS and CC induced a differential activation of the inflammasome between human macrophages and HCAEC. The mechanistic role of periodontal infection in inflammasome activation as a cause of ASVD requires further investigation.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Lipopolissacarídeos
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Colesterol
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Porphyromonas gingivalis
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Inflamassomos
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Macrófagos
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article