title: Interleukin-6 and microRNA profiles induced by oral bacteria in human atheroma derived and healthy smooth muscle cells.
abstract: BACKGROUND
  Atherosclerosis is an inflammatory disease with possible contributions from bacterial antigens. We aimed to investigate the role of oral bacteria as inducers of inflammatory cascades in smooth muscle cells from carotid endarterectomy patients (AthSMCs) and healthy controls (HSMCs).
  
  
  RESULTS
  Inactivated Streptococcus mitis, S. sanguinis, S. gorgonii, Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis were used to stimulate inflammation in HSMCs and AthSMCs. Tumor necrosis factor-α (TNFα) was used as a positive control in all stimulations. Interleukin-6 (IL-6) levels were determined from cell culture supernatants and microRNA expression profiles from cells after 24 h of bacterial stimulation. Genome wide expression (GWE) analyses were performed after 5 h stimulation. All studied bacteria induced pro inflammatory IL-6 production in both SMCs. The most powerful inducer of IL-6 was A. actinomycetemcomitans (p < 0.001). Of the 84 studied miRNAs, expression of 9 miRNAs differed significantly (p ≤ 0.001) between HSMCs and AthSMCs stimulated with inactivated bacteria or TNFα. The data was divided into two groups: high IL-6 producers (A. actinomytectemcomititans and TNFα) and low IL-6 producers (streptococcal strains and P. gingivalis). The expression of 4 miRNAs (miR-181-5p, -186-5p, -28-5p and -155-5p) differed statistically significantly (p < 0.001) between healthy HSMCs and AthSMCs in the low IL-6 producer group. According to multidimensional scaling, two gene expression clusters were seen: one in HSMCs and one AthSMCs.
  
  
  CONCLUSIONS
  Our results suggest that inactivated oral bacteria induce inflammation that is differently regulated in healthy and atherosclerotic SMCs.
authors.affiliation: Pirkanmaa Hospital District, University of Tampere School of Medicine and Fimlab Laboratories Ltd, Tampere, Finland ; Kennedy Institute of Rheumatology, University of Oxford, London, UK ; Medical School, Tampere University, Tampere, FIN-33014 Finland.
authors.forename: Tanja
authors.initials: T
authors.lastname: Pessi
authors.affiliation: Kennedy Institute of Rheumatology, University of Oxford, London, UK.
authors.forename: Leena E
authors.initials: LE
authors.lastname: Viiri
authors.affiliation: Pirkanmaa Hospital District, University of Tampere School of Medicine and Fimlab Laboratories Ltd, Tampere, Finland.
authors.forename: Emma
authors.initials: E
authors.lastname: Raitoharju
authors.affiliation: Kennedy Institute of Rheumatology, University of Oxford, London, UK.
authors.forename: Nagora
authors.initials: N
authors.lastname: Astola
authors.affiliation: Pirkanmaa Hospital District, University of Tampere School of Medicine and Fimlab Laboratories Ltd, Tampere, Finland.
authors.forename: Ilkka
authors.initials: I
authors.lastname: Seppälä
authors.affiliation: Research Unit of Molecular Epidemiology, Helmholtz Zentrum, German Research Center for Environmental Health, Munich, Germany ; Institute of Epidemiology II, Helmholtz Zentrum, German Research Center for Environmental Health, Munich, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Waldenberger
authors.affiliation: Lounatmaa Ltd, Helsinki, Finland.
authors.forename: Kari
authors.initials: K
authors.lastname: Lounatmaa
authors.affiliation: Kennedy Institute of Rheumatology, University of Oxford, London, UK.
authors.forename: Alun H
authors.initials: AH
authors.lastname: Davies
authors.affiliation: Pirkanmaa Hospital District, University of Tampere School of Medicine and Fimlab Laboratories Ltd, Tampere, Finland.
authors.forename: Terho
authors.initials: T
authors.lastname: Lehtimäki
authors.affiliation: Pirkanmaa Hospital District, University of Tampere School of Medicine and Fimlab Laboratories Ltd, Tampere, Finland.
authors.forename: Pekka J
authors.initials: PJ
authors.lastname: Karhunen
authors.affiliation: Kennedy Institute of Rheumatology, University of Oxford, London, UK.
authors.forename: Claudia
authors.initials: C
authors.lastname: Monaco
keywords: Atherosclerosis; Genome wide expression; Inflammation; Oral bacteria; Smooth muscle cells; microRNA