The proposal is designed to establish how oxidative stress caused by bleomycin treatment leads to macrophage apoptosis and lung fibrosis. The investigators postulate that this apoptotic response causes impaired clearance of lung debris and release of inflammatory cytokines, particularly IL1 beta. They present three specific aims to test the hypothesis.
Aim 1 is an in vitro study using peritoneal macrophages to determine the involvement of oxidative stress in bleomycin-induced apoptosis.
The second aim i s an in vivo study using p53 knockout animals to test the role of this protein in apoptosis and concomitant bleomycin-induced fibrosis. Third is to define the role of IL1 beta and interleukin converting enzymes in lung fibrosis.
| Davis, D W; Weidner, D A; Holian, A et al. (2000) Nitric oxide-dependent activation of p53 suppresses bleomycin-induced apoptosis in the lung. J Exp Med 192:857-69 |
| McConkey, D J (1998) Biochemical determinants of apoptosis and necrosis. Toxicol Lett 99:157-68 |
