Transient pulmonary fibrogenic effect induced by intratracheal instillation of ultrafine amorphous silica in A/J mice

In order to evaluate the degree of pulmonary fibrosis and to identify the fibrogenic mechanisms induced by ultrafine amorphous silica (UFAS), UFAS suspensions (similar to 50 mu l) were instilled intratracheally into A/J mice at doses of 0, 2, 10 and 50mg/kg(n=5 per group). Mice were Sacrificed at 24h. 1, 4 and 14 weeks after exposure. Gomori's trichrome staining revealed that UFAS induced severe alveolar epithelial thickening and pulmonary fibrosis at I week, though animals almost recovered at 4 and 14 weeks. The mRNA and protein levels of cytokines (IL-4, IL-10, IL-13 and IFN-gamma), matrix metalloproteinases (MMP-2, MMP-9 and MMP-10) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in lung tissues were significantly elevated at 24 h and I week post-treatment, though these levels decreased to near the control range at 4 and 14 weeks except IFN-gamma and MMP-2. These results demonstrate that UFAS can induce pulmonary fibrosis in the same way as crystalline silica. However, the degree of fibrosis observed was transient. This study shows that cytokines (IL-4, IL-10, IL-13 and IFN-gamma), MMPs (MMP-2, MMP-9 and MMP-10) and TIMP-1 play important roles in the fibrosis induced by the intratracheal instillation of UFAS. (C) 2008 Elsevier Ireland Ltd. All rights reserved.