Document Detail

Increased alveolar concentration of nitric oxide is related to serum-induced lung fibroblast proliferation in patients with systemic sclerosis.
MedLine Citation:
PMID:  20595271     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: Lung inflammation is present in patients with systemic sclerosis (SSc) and interstitial lung disease (ILD), but the mechanisms linking inflammatory and fibrotic processes in ILD are unknown. Our aim was to investigate whether alveolar inflammation, reflected by increased alveolar concentration of exhaled nitric oxide (C(A)NO), is related to the ability of serum from patients with SSc to induce pulmonary fibroblast proliferation (PFP) and myofibroblast conversion. METHODS: C(A)NO was measured in all subjects (37 patients with SSc and 10 healthy controls) whose sera were used to stimulate PFP (assessed by BrdU labeling index) and myofibroblast conversion (detected by alpha-smooth muscle actin expression). The PFP index in patients with SSc was compared to control values, and between patients with SSc who had elevated (> 4.3 ppb) and normal (<or= 4.3 ppb) C(A)NO values. RESULTS: Both C(A)NO and the PFP index were significantly greater in patients with SSc compared to controls. In patients with SSc, the PFP index was directly related to C(A)NO levels (r = 0.48; p = 0.002). The median PFP index was significantly higher in patients with SSc who had elevated C(A)NO (> 4.3 ppb; n = 25, median 1.1, range 0.98-1.23) than in patients with SSc who had normal C(A)NO (<or= 4.3 ppb; n = 12, median 0.93, range 0.82-1.08; p = 0.01). Similarly, myofibroblast conversion induced by SSc serum was significantly greater in patients with C(A)NO > 4.3 ppb than in patients whose C(A)NO was <or= 4.3 ppb (p < 0.001) and controls (p < 0.001). CONCLUSION: Alveolar inflammation reflected by increased nitric oxide production was related to serum-induced PFP and myofibroblast conversion, linking the active alveolitis process to cell proliferation and lung fibrosis in patients with SSc.
Thong Hua-Huy; Kiet Phong Tiev; Christiane Chéreau; Sy Duong-Quy; Jean Cabane; Anh Tuan Dinh-Xuan
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-07-01
Journal Detail:
Title:  The Journal of rheumatology     Volume:  37     ISSN:  0315-162X     ISO Abbreviation:  J. Rheumatol.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-08-02     Completed Date:  2010-11-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7501984     Medline TA:  J Rheumatol     Country:  Canada    
Other Details:
Languages:  eng     Pagination:  1680-7     Citation Subset:  IM    
Department of Physiology, University Paris Descartes, Cochin Hospital, APHP, Paris, France.
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MeSH Terms
Actins / metabolism
Blood Proteins / pharmacology*
Bromodeoxyuridine / metabolism
Cell Differentiation / drug effects
Cell Line
Cell Proliferation / drug effects
Cells, Cultured
Fibroblasts / cytology,  drug effects*,  metabolism
Middle Aged
Myocytes, Smooth Muscle / cytology,  drug effects,  metabolism
Nitric Oxide / metabolism*
Prospective Studies
Pulmonary Alveoli / metabolism*
Pulmonary Fibrosis / metabolism*
Scleroderma, Systemic / metabolism*
Serum / chemistry,  metabolism
Reg. No./Substance:
0/Actins; 0/Blood Proteins; 10102-43-9/Nitric Oxide; 59-14-3/Bromodeoxyuridine

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