US EPA

2266554 

Journal Article 

Abstract 

Exhaled nitric oxide as a possible marker for remodeling in mild asthmatics? 

Nihlberg, K; Larsson, A; Tufvesson, E; Bjermer, L; Westergren-Thorsson, G 

2010 

Yes 

American Journal of Respiratory and Critical Care Medicine
ISSN: 1073-449X
EISSN: 1535-4970 

181 

A2087 

English 

10.1164/ajrccm-conference.2010.181.1_MeetingAbstracts.A2087 

WOS:000208771001294 

is part of a larger document 3452678 Proceedings of the American Thoracic Society 2010 International Conference, May 14-19, 2010, New Orleans

RATIONALE: Exhaled Nitric Oxide (NO) indicates lower airway inflammation in asthma but increased alveolar levels have also been reported in other fibrotic lung diseases. The role by NO in fibrosis is not known. The aim of the present study was thus to investigate whether NO could have a role in fibroblast differentiation and synthesis of connective matrix components as the proteoglycan versican. Versican has previously shown to be related to bronchial hyperresponsiveness in asthma and is believed to play an important role in airway inflammation and remodeling.

METHODS: Central bronchial (n=7) and distal parenchymal fibroblasts (n=8) were collected by bronchoscopy from symptomatic mild persistent asthma subjects. Fractional exhaled nitric oxide (FeNO) was measured at flow 50ml/s. Fibroblast collected by bronchoscopy and human fetal lung fibroblast (HFL-1) were cultured in 0.4% serum and labeled with radioactive sulfur (35S) to measure versican production. Immunohistochemistry was used to grade versican expression in biopsy specimens. To study the role of NO in versican production, HFL-1 and primary distal fibroblasts was cultured with the selective NOS2 inhibitor 1400W, the non selective NOS inhibitor L-NAME and the NO-donor Deta NONOate in different concentrations.

RESULTS: Distally-derived fibroblasts from asthmatics had a considerably higher versican production than control fibroblasts (210±24 vs. 106±58 DPM/µg, p<0.001). In addition, versican was increased in distal asthma tissue compared to controls (p<0.01). In these patients, FeNO was significantly elevated compared to the controls (75.8 ppm vs. 16.6 ppm, p<0.01). Furthermore, a correlation was found between FeNO and central versican production (r=0.622, p<0.01). Inhibition of NOS2 by 1400W enhanced versican production in distally- derived asthma fibroblasts and HFL-1 cells (6.7 and 1.5 times increase compared to non- inhibited cells, p<0.05). Inhibition of 1400W altered versican production in a dose dependent manner. Administration of L-NAME (30µM) reversed the increase by 1400W. Importantly, fibroblasts cultured together with Deta NONOte increased versican production in both asthma fibroblasts and HFL-1 cells.

CONCLUSIONS: We show that versican production from centrally and distally derived fibroblasts is enhanced in mild asthma. Moreover, administration of NO and modulation of the nitric oxide synthase activity can influence proteoglycan production. Thus, this data suggests that exhaled NO might be a possible marker not only for inflammation but also for remodeling in mild asthmatics. 

American Thoracic Society 2010 International Conference 

New Orleans, LA 

May 14-19, 2010