The significance of serum S100 calcium-binding protein A4 in silicosis

Background Silicosis is a chronic occupational pulmonary disease characterized by persistent inflammation and irreversible fibrosis. Considerable evidences now indicate that S100 calcium-binding protein A4 (S100A4) has been associated with fibrotic diseases. However, the role of S100A4 in silicosis is still unclear. Methods In this study, serum levels of S100A4, transforming growth factor-beta 1 (TGF-beta 1), connective tissue growth factor (CTGF), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) in patients with silicosis (n = 42) and control group (CG, n = 12) were measured by ELISA. S100A4 expression in lung tissues and primary alveolar macrophages (AMs) of mice with and without silicosis was detected by immunohistochemistry (IHC)/real-time PCR. The correlations between S100A4 and cytokines or lung function were assessed by Spearman's rank correlation analyses. Results Compared with CG, the levels of S100A4 were significantly increased in silicosis patients (70.84 (46.22, 102.46) ng/ml vs (49.84 (42.86, 60.02) ng/ml). The secretions of TGF-beta 1, CTGF, IL-6 and TNF-alpha in silicosis group were significantly higher than that in control group (p < 0.05). Serum S100A4 levels were positively correlated with TGF-beta 1 and IL-6, while were negatively correlated with lung function parameters including percentage of predicted forced vital capacity (FVC%pre), maximum vital capacity (Vcmax), deep inspiratory capacity (IC) and peak expiratory flow at 75% of vital capacity (PEF75). In receiver operating characteristic (ROC) analyses, S100A4 > 61.7 ng/ml had 63.4% sensitivity and 83.3% specificity for silicosis, and the area under the curve (AUC) was 0.707. Furthermore, immunostaining of lung tissues showed the accumulation of S100A4-positive cells in the areas of nodules of silicotic mice. The mRNA expression of S100A4 in the lung tissues and AMs of silicotic mice were significantly higher than controls. Conclusion These data suggested that increased S100A4 might contribute to the pathogenesis of silicosis.

Automated summary

Elevated levels of S100A4 were found in patients with silicosis and were correlated with decreased lung function. The expression of S100A4 was also increased in the lung tissues and macrophages of silicotic mice. These findings suggest that S100A4 may play a role in the pathogenesis of silicosis.