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 ( approximately 50microl) 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 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-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 24h and 1week 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.
Choi
Mina
M
Department of Toxicological Research, Korea Food and Drug Administration, National Institute of Toxicological Research, Seoul 122-704, Republic of Korea.
Cho
Wan-Seob
WS
Han
Beom Seok
BS
Cho
Minjung
M
Kim
Seung Yeul
SY
Yi
Jung-Yeon
JY
Ahn
Byeongwoo
B
Kim
Seung Hee
SH
Jeong
Jayoung
J
D000280:Administration, Inhalation; D000818:Animals; D004396:Coloring Agents; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008297:Male; D020782:Matrix Metalloproteinases / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008805:Mice, Inbred A; D053758:Nanoparticles / Q000008:administration & dosage / Q000633:toxicity*; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000473:pathology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012822:Silicon Dioxide / Q000008:administration & dosage / Q000633:toxicity*
D004396:Coloring Agents; D016207:Cytokines; D018076:DNA, Complementary; D012333:RNA, Messenger; D012822:Silicon Dioxide; D020782:Matrix Metalloproteinases