title: Toll-like receptor activity in patients with obstructive sleep apnea.
abstract: BACKGROUND
  Obstructive sleep apnea (OSA) has been linked to chronic inflammation and cardiovascular diseases. Considerable evidence suggests that innate immune defense mechanisms might interact with proinflammatory pathways and contribute to atherogenesis. We hypothesized that the classical pathogen recognition receptors of the innate immune response, Toll-like receptors, are involved in modulating the inflammatory response in OSA.
  
  
  METHODS
  Expression of TLR2 and TLR4 on circulating monocytes from 29 subjects with documented OSA and 18 controls were compared with the use of flow cytometry and reverse transcription-polymerase chain reaction at baseline and after 8 weeks of continuous positive airway pressure (CPAP).
  
  
  RESULTS
  There was a significant increase in both TLR2 and TLR4 surface expression and mRNA levels on monocytes after adjustment for age, body mass index, and waist-to-hip ratio. This was paralleled by enhanced nuclear factor-κB nuclear binding and an increased release of IL-6, INF-γ, and TNF-α in OSA versus control subjects. Following 8 weeks of treatment, continuous positive airway pressure downregulated TLR2 and TLR4 expression and abrogated the release of inflammatory cytokines.
  
  
  CONCLUSIONS
  OSA is associated with enhanced expression and signaling events downstream of TLR2 and TLR4 in circulating monocytes. These observations are mitigated by CPAP therapy, which suggest that TLR2 and TLR4 activation may be involved as a signaling mechanism in immune-mediated progression of atherosclerosis in OSA.
authors.affiliation: The Veterans Affairs Western New York Healthcare System, Medical Research, Bldg 20, 151, VISN02, 3495 Bailey Avenue, 14215-1199 Buffalo, NY, USA.
authors.forename: Morohunfolu
authors.initials: M
authors.lastname: Akinnusi
authors.forename: Philippe
authors.initials: P
authors.lastname: Jaoude
authors.forename: Thomas
authors.initials: T
authors.lastname: Kufel
authors.forename: Ali A
authors.initials: AA
authors.lastname: El-Solh
mesh_terms: D000328:Adult; D050197:Atherosclerosis / Q000235:genetics / Q000276:immunology*; D045422:Continuous Positive Airway Pressure; D016207:Cytokines / Q000097:blood; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D016328:NF-kappa B / Q000097:blood; D016133:Polymerase Chain Reaction; D017286:Polysomnography; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D020181:Sleep Apnea, Obstructive / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D051195:Toll-Like Receptor 2 / Q000097:blood* / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000097:blood* / Q000235:genetics
chemical_list: D016207:Cytokines; D016328:NF-kappa B; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4