Change of heme oxygenase-1 expression in lung injury induced by chrysotile asbestos in vivo and in vitro.
Oxidative stress is thought to be the pathogenesis of pulmonary fibrosis induced by asbestos, and heme oxygenase-1 (HO-1) protects lung tissue against oxidative stress. We hypothesized that HO-1 is also associated with oxidative lung injury caused by exposure to chrysotile asbestos. This study was conducted to investigate the HO-1 expression of lungs in lung injury by chrysotile asbestos in vivo and in vitro. Male Wistar rats were administered 1 mg or 2 mg chrysotile suspended in saline by a single intratracheal instillation and were sacrificed at 3 days, 1 wk, 1 mo, 3 mo, and 6 mo of recovery time. The expression of HO-1 was observed by Western blot analysis, reverse-transcription polymerase chain reaction, and immunostaining. Protein levels of HO-1 increased at from 3 days to 6 mo following intratracheal instillation of 1 or 2 mg chrysotile. The mRNA levels of HO-1 increased at 3 mo and 6 mo following intratracheal instillation of 1 or 2 mg chrysotile. HO-1-positive cells were mainly found in the alveolar macrophages during immunostaining. We then examined HO-1 protein expression in human alveolar epithelial cells (A549). A549 cells were incubated with chrysotile at concentrations of 0, 12.5, 25, 50, and 100 microg/ml over 24 h. Increased expression of HO-1 protein was found following exposure to 25 or 50 microg/ml of chrysotile. Increased expression of HO-1 was also found at 6, 12, 24, and 48 h after exposure to 50 microg/ml of chrysotile with a peak at 24 h. These findings suggest that HO-1 is related to lung injury arising from exposure to chrysotile asbestos in vivo and in vitro.
Nagatomo
Hiroko
H
Institute of Industrial and Ecological Sciences, University of Occupational and Environmental Health, Yahatanishi, Kitakyushu, Japan. nhiroko@med.uoeh-u.ac.jp
Morimoto
Yasuo
Y
Ogami
Akira
A
Hirohashi
Masami
M
Oyabu
Takako
T
Kuroda
Kaori
K
Higashi
Toshiaki
T
Tanaka
Isamu
I
D000818:Animals; D017632:Asbestos, Serpentine / Q000008:administration & dosage / Q000633:toxicity*; D002478:Cells, Cultured; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology*; D051547:Heme Oxygenase-1 / Q000096:biosynthesis* / Q000235:genetics*; D006801:Humans; D008168:Lung / Q000201:enzymology* / Q000473:pathology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D017632:Asbestos, Serpentine; D051547:Heme Oxygenase-1