Transcriptional down-regulation of neurotrophin-3 in chronic obstructive pulmonary disease.
Chronic obstructive pulmonary disease (COPD) leads to progressive development of airflow limitation and is characterised by cough, mucus hypersecretion and inflammatory changes. These characteristic features of the disease may be modulated by neural mediators such as neurotrophins (NT). Here we examined the expression and transcriptional regulation of neurotrophins in bronchial biopsies of COPD patients and compared the data to control biopsies. Histology revealed characteristic changes in the COPD tissues, including remodelling of the epithelial lining. RT-PCR demonstrated the mRNA expression of neurotrophins in all biopsies. Immunohistochemistry confirmed the expression of different proteins. To assess changes in the transcriptional expression level, quantitative real-time PCR was carried out and revealed differential mRNA expression of neurotrophins, with marked down-regulation of NT-3 mRNA expression and constant levels of nerve growth factor (NGF), brain-derived nerve factor (BDNF), and NT-4/5 mRNA expression. The present data on neurotrophin-specific transcriptional down-regulation of NT-3 in human COPD indicate a pathophysiological role for neurotrophins in COPD.
Groneberg
David A
DA
Otto-Heubner-Centre, Pneumology and Immunology, Free University Berlin and Humboldt-University, D-13353 Berlin, Germany. david.groneberg@charite.de
Peiser
Christian
C
Eynott
Paul R
PR
Welker
Pia
P
Erbes
Reinhard
R
Witt
Christian
C
Chung
K Fan
KF
Fischer
Axel
A
D001980:Bronchi / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D020933:Neurotrophin 3 / Q000235:genetics / Q000378:metabolism*; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
D020933:Neurotrophin 3; D012333:RNA, Messenger