title: Differential inflammasome activation by Porphyromonas gingivalis and cholesterol crystals in human macrophages and coronary artery endothelial cells.
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.
authors.affiliation: Department of Periodontology, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Chantrakorn
authors.initials: C
authors.lastname: Champaiboon
authors.affiliation: Department of Periodontology, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Mahatana
authors.initials: M
authors.lastname: Poolgesorn
authors.affiliation: Department of Periodontology, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Wichaya
authors.initials: W
authors.lastname: Wisitrasameewong
authors.affiliation: Research Unit for Periodontal Disease, Immunology Laboratory, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Noppadol
authors.initials: N
authors.lastname: Sa-Ard-Iam
authors.affiliation: Research Unit for Periodontal Disease, Immunology Laboratory, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Pimprapa
authors.initials: P
authors.lastname: Rerkyen
authors.affiliation: Department of Periodontology, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand. Electronic address: r_mahanonda@yahoo.com.
authors.forename: Rangsini
authors.initials: R
authors.lastname: Mahanonda
mesh_terms: D002469:Cell Separation; D002784:Cholesterol / Q000737:chemistry*; D003331:Coronary Vessels / Q000382:microbiology; D003460:Crystallization; D042783:Endothelial Cells / Q000382:microbiology; D005434:Flow Cytometry; D006801:Humans; D058847:Inflammasomes / Q000276:immunology*; D007249:Inflammation / Q000276:immunology; D053583:Interleukin-1beta / Q000378:metabolism; D008070:Lipopolysaccharides / Q000737:chemistry*; D008264:Macrophages / Q000382:microbiology*; D009000:Monocytes / Q000382:microbiology; D010641:Phenotype; D016966:Porphyromonas gingivalis / Q000472:pathogenicity*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D058847:Inflammasomes; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D002784:Cholesterol
keywords: Atherosclerosis; Cholesterol crystals; Coronary artery endothelial cells; Human macrophages; Inflammasome activation; Periodontal disease; Porphyromonas gingivalis