title: Co-upregulation of Toll-like receptors 2 and 6 on peripheral blood cells in patients with obstructive sleep apnea.
abstract: OBJECTIVE
  Toll-like receptor (TLR) 2 can heterodimerise with TLR6 to detect diacylated lipoproteins. Hypoxia inducible factor-1 α co-ordinates selective induction of TLR2 and TLR6 during persistent hypoxia. We hypothesized that TLR 2/6 co-expression may be upregulated by chronic intermittent hypoxia with re-oxygenation (IHR) in obstructive sleep apnea (OSA).
  
  
  METHODS
  TLR2/6 expressions on blood immune cells were measured in 144 patients with sleep-disordered breathing (SDB), including primary snoring (PS, n = 24), moderate to severe OSA (MSO, n = 60), very severe OSA (VSO, n = 36), and very severe OSA on continuous positive airway pressure (CPAP) treatment (VSOC, n = 24). An in vitro IHR experiment was also undertaken.
  
  
  RESULTS
  Patients in both the MSO and VSO groups had increased TLR2/6 co-expression on CD16(+) neutrophil than those in the PS group. Patients in the VSOC group had reduced TLR2/6 co-expression on neutrophil than those in either the MSO or VSO group. Blood absolute neutrophil count was positively but weakly correlated with TLR2/6 co-expression on neutrophil. TLR2/6 co-expressions on both CD14(+) monocyte and CD3(+)CD4(+)T helper cell, and TLR2 expressions on both monocyte and T helper cell in SDB patients with low Minimum SaO₂ (≦70%) were all higher than those with high Minimum SaO₂. In vitro IHR for 1-4 days resulted in TLR2/6 co-upregulation on both neutrophil and monocyte.
  
  
  CONCLUSIONS
  OSA patients had increased TLR2/6 co-expressions on blood immune cells, which were related to their immune cell counts and could be reversed with CPAP treatment. In vitro IHR could induce TLR2/6 co-upregulation.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan, yungchechen@yahoo.com.tw.
authors.forename: Yung-Che
authors.initials: YC
authors.lastname: Chen
authors.forename: Mao-Chang
authors.initials: MC
authors.lastname: Su
authors.forename: Chia-Wei
authors.initials: CW
authors.lastname: Liou
authors.forename: Shih-Feng
authors.initials: SF
authors.lastname: Liu
authors.forename: Chung-Jen
authors.initials: CJ
authors.lastname: Chen
authors.forename: Hsin-Ching
authors.initials: HC
authors.lastname: Lin
authors.forename: Chang-Chun
authors.initials: CC
authors.lastname: Hsiao
authors.forename: Ting-Ya
authors.initials: TY
authors.lastname: Wang
authors.forename: Chin-Chou
authors.initials: CC
authors.lastname: Wang
authors.forename: Chien-Hung
authors.initials: CH
authors.lastname: Chin
authors.forename: Kuo-Tung
authors.initials: KT
authors.lastname: Huang
authors.forename: An-Shen
authors.initials: AS
authors.lastname: Lin
authors.forename: Meng-Chih
authors.initials: MC
authors.lastname: Lin
mesh_terms: D000328:Adult; D045422:Continuous Positive Airway Pressure; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism*; D017286:Polysomnography; D012016:Reference Values; D020181:Sleep Apnea, Obstructive / Q000235:genetics* / Q000276:immunology* / Q000628:therapy; D051195:Toll-Like Receptor 2 / Q000235:genetics*; D051216:Toll-Like Receptor 6 / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics*
chemical_list: C495342:TLR2 protein, human; C495368:TLR6 protein, human; D051195:Toll-Like Receptor 2; D051216:Toll-Like Receptor 6