Effect of long-term inhalation of toner on extracellular matrix in the lungs of rats in vivo.
We assessed the effects of long-term inhalation of toner on the pathological changes and gene expression with the synthesis and degradation of collagenous extracellular matrix in a rat model. Female Wistar rats (10 wk old) were divided evenly into a high concentration exposure group (H: 15.2 mg/m3), a low concentration exposure group (L: 5.5 mg/m3), and a control group. The mass median aerodynamic diameter of toner was 4.5 microm. The rats were sacrificed at the termination of a 1-yr or 2-yr inhalation period. Pathological examination was performed from the left lung, and transcriptional levels of mRNA extracted from the right lung were assessed by semiquantitative reverse-transcription polymerase chain polymerase (RT-PCR). The pathological findings showed mild pulmonary fibrosis in 20% (L, 1 yr), 40% (H, 1 yr), 56% (L, 2 yr) and 62% (H, 2 yr), while lung cancer was not observed in any of the exposed groups. In the 1-yr high-concentration group, gene expression of matrix metalloproteinase-2 (MMP-2) and type I collagen mRNA in the rat lungs increased, while tissue inhibitors of metalloproteinase-2 (TIMP-2) decreased. The 2-yr high-concentration group increased in message level of type I collagen and TIMP-2 but not that of MMP-2. These data suggested that results of gene expression of MMP, TIMP, and collagen in the 2-yr exposure may lead to accumulation of collagen compared to the 1-yr exposure, and that the imbalance of the expression of MMPs, TIMPs, and extracellular matrix might be associated with pulmonary fibrosis induced by toner.
Morimoto
Yasuo
Y
Institute of Industrial and Ecological Sciences, University of Occupational and Environmental Health, Kitakyushu, Japan. yasuom@med.uoeh-u.ac.jp
Kim
Heungnam
H
Oyabu
Takako
T
Hirohashi
Masami
M
Nagatomo
Hiroko
H
Ogami
Akira
A
Yamato
Hiroshi
H
Higashi
Toshiaki
T
Tanaka
Isamu
I
Kasai
Takahiko
T
D000280:Administration, Inhalation; D000818:Animals; D024042:Collagen Type I / Q000096:biosynthesis* / Q000235:genetics; D005109:Extracellular Matrix / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007281:Ink; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000235:genetics; D008855:Microscopy, Electron, Scanning; D011327:Printing; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000378:metabolism; D036401:Toxicity Tests, Chronic; D014132:Trachea / Q000187:drug effects
D024042:Collagen Type I; D012333:RNA, Messenger; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2