TY - JOUR T1 - Increased Alveolar Concentration of Nitric Oxide Is Related to Serum-induced Lung Fibroblast Proliferation in Patients with Systemic Sclerosis JF - The Journal of Rheumatology JO - J Rheumatol DO - 10.3899/jrheum.090915 SP - jrheum.090915 AU - Thong Hua-Huy AU - Kiet Phong Tiev AU - Christiane Chéreau AU - Sy Duong-Quy AU - Jean Cabane AU - Anh Tuan Dinh-Xuan Y1 - 2010/07/01 UR - http://www.jrheum.org/content/early/2010/06/28/jrheum.090915.abstract N2 - 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 (CANO), is related to the ability of serum from patients with SSc to induce pulmonary fibroblast proliferation (PFP) and myofibroblast conversion. Methods CANO 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 α-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 (≤ 4.3 ppb) CANO values. Results Both CANO 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 CANO levels (r = 0.48; p = 0.002). The median PFP index was significantly higher in patients with SSc who had elevated CANO (> 4.3 ppb; n = 25, median 1.1, range 0.98–1.23) than in patients with SSc who had normal CANO (≤ 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 CANO > 4.3 ppb than in patients whose CANO was ≤ 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. ER -