Differential inflammasome activation by Porphyromonas gingivalis and cholesterol crystals in human macrophages and coronary artery endothelial cells

• Published in: Atherosclerosis 2014-07, Vol.235 (1), p.38-44
• Main Authors: Champaiboon, Chantrakorn, Poolgesorn, Mahatana, Wisitrasameewong, Wichaya, Sa-Ard-Iam, Noppadol, Rerkyen, Pimprapa, Mahanonda, Rangsini
• Format: Article
• Language: English
• Subjects: Atherosclerosis; Cardiovascular; Cell Separation; Cholesterol - chemistry; Cholesterol crystals; Coronary artery endothelial cells; Coronary Vessels - microbiology; Crystallization; Endothelial Cells - microbiology; Flow Cytometry; Human macrophages; Humans; Inflammasome activation; Inflammasomes - immunology; Inflammation - immunology; Interleukin-1beta - metabolism; Lipopolysaccharides - chemistry; Macrophages - microbiology; Monocytes - microbiology; Periodontal disease; Phenotype; Porphyromonas gingivalis; Porphyromonas gingivalis - pathogenicity; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2014.04.007

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)-1β, 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-1β. 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-1β from P. gingivalis LPS-primed M1 and M2 macrophages treated with CC. Unlike macrophages, HCAEC showed no release of IL-1β 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-1β. The amount of IL-1β 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.