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

• Published in: Toxicology letters Vol. 182; no. 1; pp. 97 - 101
• Main Authors: Choi, Mina, Cho, Wan-Seob, Han, Beom Seok, Cho, Minjung, Kim, Seung Yeul, Yi, Jung-Yeon, Ahn, Byeongwoo, Kim, Seung Hee, Jeong, Jayoung
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 10.11.2008; Elsevier
• Subjects: Administration, Inhalation; Animals; Biological and medical sciences; Coloring Agents; Cytokines; Cytokines - biosynthesis; Cytokines - genetics; DNA, Complementary - biosynthesis; DNA, Complementary - genetics; Image Processing, Computer-Assisted; Immunohistochemistry; Male; Matrix Metalloproteinases - biosynthesis; Matrix Metalloproteinases - genetics; Medical sciences; Mice; Mice, Inbred A; MMPs; Nanoparticles - administration & dosage; Nanoparticles - toxicity; Pneumology; Pulmonary fibrosis; Pulmonary Fibrosis - chemically induced; Pulmonary Fibrosis - pathology; Respiratory system : syndromes and miscellaneous diseases; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Silicon Dioxide - administration & dosage; Silicon Dioxide - toxicity; TIMP-1; Toxicology; Ultrafine amorphous silica; Ultrafine amorphous silica; Pulmonary fibrosis; TIMP-1; Cytokines; MMPs; Lung disease; Enzyme; Respiratory disease; Lung; Rodentia; Cytokine; Tissue inhibitor metalloproteinase 1; Metalloendopeptidases; Respiratory system; Silica; Transitory; Inorganic compound; Peptidases; Vertebrata; Mammalia; Mouse; Animal; Hydrolases; Intratracheal administration
• ISSN: 0378-4274; 1879-3169
• DOI: 10.1016/j.toxlet.2008.08.019

In order to evaluate the degree of pulmonary fibrosis and to identify the fibrogenic mechanisms induced by ultrafine amorphous silica (UFAS), UFAS suspensions (∼50 μl) were instilled intratracheally into A/J mice at doses of 0, 2, 10 and 50 mg/kg ( n = 5 per group). Mice were sacrificed at 24 h, 1, 4 and 14 weeks after exposure. Gomori’s trichrome staining revealed that UFAS induced severe alveolar epithelial thickening and pulmonary fibrosis at 1 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-γ), 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 1 week post-treatment, though these levels decreased to near the control range at 4 and 14 weeks except IFN-γ 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-γ), MMPs (MMP-2, MMP-9 and MMP-10) and TIMP-1 play important roles in the fibrosis induced by the intratracheal instillation of UFAS.