Transcriptional down-regulation of neurotrophin-3 in chronic obstructive pulmonary disease

Abstract

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.

Pan‐neurotrophin receptor p75NTR expression is strongly induced in lesional atopic mast cells

“…A marked down‐regulation of NT‐3 mRNA expression and constant levels of NGF, BDNF, and NT‐4/5 mRNA expression were shown. Together with the present data on p75NTR, these data on neurotrophin‐specific transcriptional down‐regulation of NT‐3 in human COPD indicate that there may be disease‐ and cell type‐specific differences in the regulation of the expression of neurotrophins and their receptors [27]. Changes observed may therefore not present an epiphenomenon of the inflammatory processes but could be considered to be disease‐specific and related to the microenvironment.…”

“…This ligand may also play a role in chronic inflammatory diseases and only a limited number of studies assessed the regulation of this p75NTR ligand in chronic inflammation. Whereas NGF seems to be induced under the state of chronic inflammation, a recent study pointed to a potential down‐regulation of NT‐3 in chronic inflammatory diseases such as chronic obstructive pulmonary disease (COPD) [27]. For this disease that is currently the fourth most common cause of death in the world, real‐time PCR studies revealed a differential mRNA expression of neurotrophins.…”

Cell type‐specific regulation of brain‐derived neurotrophic factor in states of allergic inflammation

“…A differential regulation for NTs with a reduction vs. induction of different molecules has so far only been demonstrated for a limited number of pathological states [32]. By combining the data of the present and previous studies, it can be concluded that the NT system does not act uniformly with an up-regulation of gene expression towards any inflammatory stimulus as shown, i.e.…”

Transcriptional down-regulation of suppressor of cytokine signaling (SOCS)-3 in chronic obstructive pulmonary disease

“…Since there are no data available on the expression of this important cytokine signal inhibitor in COPD, the aim of the present study was to address the transcriptional expression level of SOCS-3 along with SOCS-4 and SOCS-5 in bronchial tissues of a previously characterized cohort of COPD patients [12,22]. …”