title: Expression of interferon-γ, interferon-α and related genes in individuals with Down syndrome and periodontitis.
abstract: BACKGROUND
  Recently, attenuation of anti-inflammatory and increase of pro-inflammatory mediators was demonstrated in individuals with Down syndrome (DS) in comparison with euploid patients during periodontal disease (PD), suggesting a shift to a more aggressive inflammation in DS.
  
  
  OBJECTIVE
  To determine the influence of DS in the modulation of interferons (IFNs) signaling pathway in PD.
  
  
  METHODS
  Clinical periodontal assessment was performed and gingival tissue samples obtained from a total of 51 subjects, including 19 DS individuals with PD, 20 euploid individuals with PD and 12 euploid individuals without PD. Expression levels of interferon-gamma (IFNG) and interferon-alpha (IFNA), and their receptors IFNGR1, IFNGR2, IFNAR1 and IFNAR2, the signaling intermediates Janus kinase 1 (JAK1), signal transducer and activator of transcription 1 (STAT1) and interferon regulatory factor 1 (IRF1) were determined using real time quantitative polymerase chain reaction (qPCR).
  
  
  RESULTS
  Clinical signs of periodontal disease were markedly more severe in DS and euploid patients with PD in comparison to euploid and periodontally healthy patients. There was no difference on mRNA levels of IFNA, IFNG, INFGR2, IFNAR1 and IFNAR2 between DS and euploid individuals, even though some of these genes are located on chromosome 21. STAT1 and IRF1 mRNA levels were significantly lower in DS patients in comparison with euploid individuals with PD. In euploid individuals, PD was associated with an increased expression of IFNGR1, IFNGR2, IFNAR1, STAT1 and IRF1.
  
  
  CONCLUSIONS
  Reduced expression of STAT1 and IRF1 genes indicate an impaired activation of IFNs signaling in individuals with DS and PD. Expression of IFNA, IFNG and IFN receptors was not altered in DS patients, indicating that indirect mechanisms are involved in the reduced activation of IFN signaling.
authors.affiliation: Department of Orthodontics and Pediatric Dentistry, School of Dentistry at Araraquara, UNESP - Univ. Estadual Paulista, São Paulo, Brazil.
authors.forename: Marcia H
authors.initials: MH
authors.lastname: Tanaka
authors.forename: Elisa M A
authors.initials: EM
authors.lastname: Giro
authors.forename: Lícia B
authors.initials: LB
authors.lastname: Cavalcante
authors.forename: Juliana R
authors.initials: JR
authors.lastname: Pires
authors.forename: Luciano H
authors.initials: LH
authors.lastname: Apponi
authors.forename: Sandro R
authors.initials: SR
authors.lastname: Valentini
authors.forename: Denise M P
authors.initials: DM
authors.lastname: Spolidório
authors.forename: Marisa V
authors.initials: MV
authors.lastname: Capela
authors.forename: Carlos
authors.initials: C
authors.lastname: Rossa
authors.forename: Raquel M
authors.initials: RM
authors.lastname: Scarel-Caminaga
mesh_terms: D000328:Adult; D004314:Down Syndrome / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D050856:Interferon Regulatory Factor-1 / Q000378:metabolism; D016898:Interferon-alpha / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism*; D053613:Janus Kinase 1 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010518:Periodontitis / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D053633:Receptor, Interferon alpha-beta / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D017471:Receptors, Interferon / Q000235:genetics / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D055815:Young Adult; D000096743:Interferon gamma Receptor
chemical_list: D050856:Interferon Regulatory Factor-1; D016898:Interferon-alpha; D007371:Interferon-gamma; D053613:Janus Kinase 1; D012333:RNA, Messenger; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon; D050794:STAT1 Transcription Factor; D000096743:Interferon gamma Receptor; C507964:IFNAR1 protein, human; C508033:IFNAR2 protein, human; C086185:IFNGR2 protein, human; C494257:IRF1 protein, human; C494079:STAT1 protein, human