TY - JOUR
T1 - Neurotrophins and tonsillar hypertrophy in children with obstructive sleep apnea
AU - Goldbart, Aviv D.
AU - Mager, Edward
AU - Veling, Maria C.
AU - Goldman, Julie L.
AU - Kheirandish-Gozal, Leila
AU - Serpero, Laura D.
AU - Piedimonte, Giovanni
AU - Gozal, David
N1 - Funding Information:
This research was supported by the POSCO and by the World Class University (WCU) program through the National Research Foundation (Grant#R32-10147). MGL appreciate the support by the National Research Foundation of Korea (ERC Program, Grant #2012R1A5A1048294).
PY - 2007/10/1
Y1 - 2007/10/1
N2 - Enlarged adenotonsillar tissue (AT) is a major determinant of obstructive sleep apnea (OSA) severity in children; however, mechanisms of AT proliferation are poorly understood. We hypothesized that early exposure to respiratory syncytial virus (RSV) may modify AT proliferation through up-regulation of nerve growth factor (NGF)-neurokinin 1 (NK1) receptor dependent pathways. AT harvested from 34 children with OSA and 25 children with recurrent tonsillitis (RI) were examined for mRNA expression of multiple growth factors and their receptors. In addition, NK1 receptor expression and location, and substance P tissue concentrations were compared in AT from OSA and RI children. NGF mRNA and its high-affinity tyrosine kinase receptor (trkA) expression were selectively increased in OSA (p < 0.001). NK1 receptor mRNA and protein expression were also enhanced in OSA (p < 0.01), and substance P concentrations in OSA patients were higher than in RI (p < 0.0001). AT from OSA children exhibit distinct differences in the expression of NGF and trkA receptors, NK1 receptors, and substance P. The homology between these changes and those observed in the lower airways following RSV infection suggests that RSV may have induced neuro-immunomodulatory changes within AT, predisposing them to increased proliferation, and ultimately contribute to emergence of OSA.
AB - Enlarged adenotonsillar tissue (AT) is a major determinant of obstructive sleep apnea (OSA) severity in children; however, mechanisms of AT proliferation are poorly understood. We hypothesized that early exposure to respiratory syncytial virus (RSV) may modify AT proliferation through up-regulation of nerve growth factor (NGF)-neurokinin 1 (NK1) receptor dependent pathways. AT harvested from 34 children with OSA and 25 children with recurrent tonsillitis (RI) were examined for mRNA expression of multiple growth factors and their receptors. In addition, NK1 receptor expression and location, and substance P tissue concentrations were compared in AT from OSA and RI children. NGF mRNA and its high-affinity tyrosine kinase receptor (trkA) expression were selectively increased in OSA (p < 0.001). NK1 receptor mRNA and protein expression were also enhanced in OSA (p < 0.01), and substance P concentrations in OSA patients were higher than in RI (p < 0.0001). AT from OSA children exhibit distinct differences in the expression of NGF and trkA receptors, NK1 receptors, and substance P. The homology between these changes and those observed in the lower airways following RSV infection suggests that RSV may have induced neuro-immunomodulatory changes within AT, predisposing them to increased proliferation, and ultimately contribute to emergence of OSA.
UR - http://www.scopus.com/inward/record.url?scp=34748922976&partnerID=8YFLogxK
U2 - 10.1203/PDR.0b013e31814257ed
DO - 10.1203/PDR.0b013e31814257ed
M3 - Article
C2 - 17667845
AN - SCOPUS:34748922976
SN - 0031-3998
VL - 62
SP - 489
EP - 494
JO - Pediatric Research
JF - Pediatric Research
IS - 4
ER -
