title: Recent exposure to ultrafine particles in school children alters miR-222 expression in the extracellular fraction of saliva.
abstract: Ultrafine particles (<100 nm) are ubiquitous present in the air and may contribute to adverse cardiovascular effects. Exposure to air pollutants can alter miRNA expression, which can affect downstream signaling pathways. miRNAs are present both in the intracellular and extracellular environment. In adults, miR-222 and miR-146a were identified as associated with particulate matter exposure. However, there is little evidence of molecular effects of ambient air pollution in children. This study examined whether exposure to fine and ultrafine particulate matter (PM) is associated with changes in the extracellular content of miR-222 and miR-146a of children.
  
  
  
  Saliva was collected from 80 children at two different time points, circa 11 weeks apart and stabilized for RNA preservation. The extracellular fraction of saliva was obtained by means of differential centrifugation and ultracentrifugation. Expression levels of miR-222 and miR-146a were profiled by qPCR. We regressed the extracellular miRNA expression against recent exposure to ultrafine and fine particles measured at the school site using mixed models, while accounting for sex, age, BMI, passive smoking, maternal education, hours of television use, time of the day and day of the week.
  
  
  
  Exposure to ultrafine particles (UFP) at the school site was positively associated with miR-222 expression in the extracellular fraction in saliva. For each IQR increase in particles in the class room (+8504 particles/cm(3)) or playground (+28776 particles/cm(3)), miR-222 was, respectively 23.5 % (95 % CI: 3.5 %-41.1 %; p = 0.021) or 29.9 % (95 % CI:10.6 %-49.1 %; p = 0.0027) higher. No associations were found between miR-146a and recent exposure to fine and ultrafine particles.
  
  
  
  Our results suggest a possible epigenetic mechanism via which cells respond rapidly to small particles, as exemplified by miR-222 changes in the extracellular fraction of saliva.
authors.affiliation: Centre for Environmental Sciences, Hasselt University, Agoralaan, building D, 3590, Diepenbeek, Belgium.
authors.forename: Annette
authors.initials: A
authors.lastname: Vriens
authors.affiliation: Centre for Environmental Sciences, Hasselt University, Agoralaan, building D, 3590, Diepenbeek, Belgium. tim.nawrot@uhasselt.be.|Department of Public Health & Primary Care, Leuven University, Leuven, Belgium. tim.nawrot@uhasselt.be.
authors.forename: Tim S
authors.initials: TS
authors.lastname: Nawrot
authors.affiliation: Centre for Environmental Sciences, Hasselt University, Agoralaan, building D, 3590, Diepenbeek, Belgium.
authors.forename: Nelly D
authors.initials: ND
authors.lastname: Saenen
authors.affiliation: Centre for Environmental Sciences, Hasselt University, Agoralaan, building D, 3590, Diepenbeek, Belgium.|Environmental Risk and Health, Flemish Institute for Technological Research (VITO), Mol, Belgium.
authors.forename: Eline B
authors.initials: EB
authors.lastname: Provost
authors.affiliation: Centre for Environmental Sciences, Hasselt University, Agoralaan, building D, 3590, Diepenbeek, Belgium.
authors.forename: Michal
authors.initials: M
authors.lastname: Kicinski
authors.affiliation: Environmental Risk and Health, Flemish Institute for Technological Research (VITO), Mol, Belgium.
authors.forename: Wouter
authors.initials: W
authors.lastname: Lefebvre
authors.affiliation: Belgian Interregional Environment Agency, Brussel, Belgium.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Vanpoucke
authors.affiliation: Laboratory of Experimental Cancer Research, Department of Radiation Oncology and Experimental Cancer Research, Ghent University Hospital, Ghent, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Van Deun
authors.affiliation: Laboratory of Experimental Cancer Research, Department of Radiation Oncology and Experimental Cancer Research, Ghent University Hospital, Ghent, Belgium.
authors.forename: Olivier
authors.initials: O
authors.lastname: De Wever
authors.affiliation: Centre for Environmental Sciences, Hasselt University, Agoralaan, building D, 3590, Diepenbeek, Belgium.
authors.forename: Karen
authors.initials: K
authors.lastname: Vrijens
authors.affiliation: Centre for Environmental Sciences, Hasselt University, Agoralaan, building D, 3590, Diepenbeek, Belgium.|Environmental Risk and Health, Flemish Institute for Technological Research (VITO), Mol, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: De Boever
authors.affiliation: Centre for Environmental Sciences, Hasselt University, Agoralaan, building D, 3590, Diepenbeek, Belgium.|MRC/PHE Centre for Environment and Health, School of Public Health, Imperial College, London, UK.
authors.forename: Michelle
authors.initials: M
authors.lastname: Plusquin
mesh_terms: D000393:Air Pollutants / Q000032:analysis*; D016902:Air Pollution, Indoor / Q000032:analysis; D002648:Child; D004784:Environmental Monitoring; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D010316:Particle Size; D052638:Particulate Matter / Q000032:analysis*; D012463:Saliva / Q000378:metabolism*
chemical_list: D000393:Air Pollutants; D035683:MicroRNAs; D052638:Particulate Matter; C542542:MIRN146 microRNA, human; C525710:MIR222, human
keywords: Children; Extracellular miRNA; Saliva; Ultrafine air pollution