title: A pro-inflammatory role for nuclear factor kappa B in childhood obstructive sleep apnea syndrome.
abstract: OBJECTIVE
  Childhood obstructive sleep apnea syndrome (OSAS) is associated with an elevation of inflammatory markers such as C-reactive protein (CRP) that correlates with specific morbidities and subsides following intervention. In adults, OSAS is associated with activation of the transcription factor nuclear factor kappa B (NF-kB). We explored the mechanisms underlying NF-kB activation, based on the hypothesis that specific NF-kB signaling is activated in children with OSAS.
  
  
  METHODS
  Adenoid and tonsillar tissues from children with OSAS and matched controls were immunostained against NF-kB classical (p65 and p50) and alternative (RelB and p52) pathway subunits, and NF-kB-dependent cytokines: interleukin (IL)- 1α, IL-1β, tumor necrosis factor-α, and IL-8). Serum CRP levels were measured in all subjects. NF-kB induction was evaluated by a luciferase-NF-kB reporter assay in L428 cells constitutively expressing NF-kB and in Jurkat cells with inducible NF-kB expression. p65 translocation to the nucleus, reflecting NF-kB activation, was measured in cells expressing fluorescent NF-kB-p65-GFP (green fluorescent protein).
  
  
  METHODS
  Sleep research laboratory.
  
  
  METHODS
  Twenty-five children with OSAS and 24 without OSAS.
  
  
  METHODS
  N/A.
  
  
  RESULTS
  Higher expression of IL-1α and classical NF-kB subunits p65 and p50 was observed in adenoids and tonsils of children with OSAS. Patient serum induced NF-kB activity, as measured by a luciferase-NF-kB reporter assay and by induction of p65 nuclear translocation in cells permanently transfected with GFP-p65 plasmid. IL-1β showed increased epithelial expression in OSAS tissues.
  
  
  CONCLUSIONS
  Nuclear factor kappa B is locally and systemically activated in children with obstructive sleep apnea syndrome. This observation may motivate the search for new anti-inflammatory strategies for controlling nuclear factor kappa B activation in obstructive sleep apnea syndrome.
authors.affiliation: Department of Microbiology and Immunology ; Pediatric Pulmonary and Sleep Research Laboratory.
authors.forename: Lee P
authors.initials: LP
authors.lastname: Israel
authors.forename: Daniel
authors.initials: D
authors.lastname: Benharoch
authors.forename: Jacob
authors.initials: J
authors.lastname: Gopas
authors.forename: Aviv D
authors.initials: AD
authors.lastname: Goldbart
mesh_terms: D000234:Adenoids / Q000502:physiology; D002097:C-Reactive Protein / Q000032:analysis; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D053582:Interleukin-1alpha / Q000502:physiology; D053583:Interleukin-1beta / Q000502:physiology; D016209:Interleukin-8 / Q000502:physiology; D008297:Male; D016328:NF-kappa B / Q000502:physiology*; D014066:Palatine Tonsil / Q000502:physiology; D020181:Sleep Apnea, Obstructive / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D016209:Interleukin-8; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein
keywords: Inflammation; nuclear factor kappa B; sleep disordered breathing