title: Porphyromonas gingivalis lipopolysaccharide alters atherosclerotic-related gene expression in oxidized low-density-lipoprotein-induced macrophages and foam cells.
abstract: OBJECTIVE
  The molecular mechanism linking atherosclerosis formation and periodontal pathogens is not clear, although a positive correlation between periodontal infections and cardiovascular diseases has been reported. The aim of this study was to determine whether stimulation with Porphyromonas gingivalis lipopolysaccharide (LPS) affected the expression of atherosclerosis-related genes, during and after the formation of foam cells.
  
  
  METHODS
  Macrophages from human THP-1 monocytes were treated with oxidized low-density lipoprotein (oxLDL) to induce the formation of foam cells. P. gingivalis LPS was added to cultures of either oxLDL-induced macrophages or foam cells. The expression of atherosclerosis-related genes was assayed by quantitative real-time PCR, and the production of granulocyte-macrophage colony-stimulating factor, monocyte chemotactic protein-1, interleukin (IL)-1β, IL-10 and IL-12 proteins was determined using ELISA. Nuclear translocation of nuclear factor-kappaB (NF-κB) P(65) was detected by immunocytochemistry, and western blotting was used to evaluate inhibitory kappa B-α (IκΒ-α) degradation to confirm activation of the NF-κB pathway.
  
  
  RESULTS
  P. gingivalis LPS stimulated atherosclerosis-related gene expression in foam cells and increased the oxLDL-induced expression of chemokines, adhesion molecules, growth factors, apoptotic genes and nuclear receptors in macrophages. Transcription of the proinflammatory cytokines IL1β and IL12 was elevated in response to LPS in both macrophages and foam cells, whereas transcription of the anti-inflammatory cytokine, IL10, was not affected. Increased activation of the NF-κB pathway was also observed in macrophages costimulated with LPS + oxLDL.
  
  
  CONCLUSIONS
  P. gingivalis LPS appears to be an important factor in the development of atherosclerosis by stimulation of atherosclerosis-related gene expression in both macrophages and foam cells via activation of the NF-κB pathway.
authors.affiliation: School and Hospital of Stomatology, Fujian Medical University, Fuzhou, China.
authors.forename: L
authors.initials: L
authors.lastname: Lei
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.forename: F
authors.initials: F
authors.lastname: Yan
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: Y
authors.initials: Y
authors.lastname: Xiao
mesh_terms: D017209:Apoptosis / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics*; D015815:Cell Adhesion Molecules / Q000032:analysis; D018929:Cell Culture Techniques; D002460:Cell Line; D018932:Chemokine CCL2 / Q000032:analysis; D018925:Chemokines / Q000032:analysis; D005487:Foam Cells / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000032:analysis; D006801:Humans; D020672:I-kappa B Proteins / Q000032:analysis; D018836:Inflammation Mediators / Q000032:analysis; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis; D016753:Interleukin-10 / Q000032:analysis; D018664:Interleukin-12 / Q000032:analysis; D053583:Interleukin-1beta / Q000032:analysis; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects*; D009000:Monocytes / Q000187:drug effects; D016328:NF-kappa B / Q000032:analysis; D010084:Oxidation-Reduction; D016966:Porphyromonas gingivalis; D018160:Receptors, Cytoplasmic and Nuclear / Q000032:analysis
chemical_list: D015815:Cell Adhesion Molecules; D018932:Chemokine CCL2; D018925:Chemokines; D020672:I-kappa B Proteins; D018836:Inflammation Mediators; D036341:Intercellular Signaling Peptides and Proteins; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D008077:Lipoproteins, LDL; D016328:NF-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; C099252:oxidized low density lipoprotein; D016753:Interleukin-10; D018664:Interleukin-12; D016178:Granulocyte-Macrophage Colony-Stimulating Factor