Apoptotic cell instillation results in elevated TGF-B and apoptosis-induced-apoptosis in rat lung.
Wang-L; Scabilloni-J; Antonini-J; Rojanasakul-Y; Castranova-V; Mercer-R
Toxicologist 2004 Mar; 78(S-1):337
Results from animal inhalation with either high burden or highly toxic particles showed increased apoptosis in the lungs. Previous studies by our group indicated that pulmonary administration of apoptotic lung cells induced inflammatory cell influx and lung fibrosis, indicating a direct linkage between apoptosis and fibrotic lung disorders (Ref.1). In this study, we further characterized the kinetics of pulmonary response to apoptotic cell instillation in rats and investigated the possible role of TGF-B in this process. Rats instilled with apoptotic cells showed a decrease in lung cell apoptosis at 1 week post-treatment, consistent with our previous finding showing the clearance of labeled apoptotic cells in rat lungs after 1 week (Ref.2). However, the level of lung cell apoptosis was higher at 4 and 12 weeks post-treatment compared to the control groups instilled with normal non-apoptotic cells. These results suggest that the apoptotic cells observed at latter time points were not those originally instilled but were subsequently induced after the treatment. Analysis of BAL fluids from treated rats showed an increase in TGF-B expression at 1 and 4 week post-treatment compared to the control groups. TGF-B is a known inducer of apoptosis and a key mediator of lung fibrosis, our results therefore suggest that increased TGF-B by apoptotic cell instillation may be responsible for the increased lung cell death and subsequent development of pulmonary fibrosis.
Laboratory-animals; Animals; Animal-studies; Inhalation-studies; Lung-burden; Toxic-effects; Lung-disorders; Pulmonary-system-disorders; Respiratory-system-disorders; Fibrosis
The Toxicologist. Society of Toxicology 43nd Annual Meeting and ToxExpo, March 21-25, 2004, Baltimore, Maryland