A Pro-Inflammatory Role for Nuclear Factor Kappa B in Childhood Obstructive Sleep Apnea Syndrome

• Published in: Sleep (New York, N.Y.) Vol. 36; no. 12; pp. 1947 - 1955
• Main Authors: Israel, Lee P., Benharoch, Daniel, Gopas, Jacob, Goldbart, Aviv D.
• Format: Journal Article
• Language: English
• Published: United States Associated Professional Sleep Societies, LLC 01.12.2013
• Subjects: Adenoids - physiology; C-Reactive Protein - analysis; Case-Control Studies; Child; Child, Preschool; Female; Humans; Inflammation - physiopathology; Interleukin-1alpha - physiology; Interleukin-1beta - physiology; Interleukin-8 - physiology; Male; NF-kappa B - physiology; Palatine Tonsil - physiology; Pro-Inflammatory Role for NF-kB in Childhood OSA Syndrome; Sleep Apnea, Obstructive - physiopathology; Tumor Necrosis Factor-alpha - physiology; sleep disordered breathing; Inflammation; nuclear factor kappa B
• ISSN: 0161-8105; 1550-9109; 1550-9109
• DOI: 10.5665/sleep.3236

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. 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). Sleep research laboratory. Twenty-five children with OSAS and 24 without OSAS. N/A. 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. 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.