Induction of p21WAF/CIP1 during hyperoxia

p21(WAF/CIP1) is an important regulator of cell cycle progression (1-4). When induced, p21(WAF/CIP1) protein inhibits cell cycle progression at the G(1)/S interface, resulting in growth arrest of the cell. To determine if p21(WAF/CIP1) is involved in growth arrest and lung injury during hyperoxia, several cell lines were exposed to high levels of hyperoxia. p21(WAF/CIP1) was found to be induced by 72 h in all three cell lines. Next, using an in vivo model, p21(WAF/CIP1) was found to be induced at both the mRNA and protein level in neonatal murine lung born and maintained in hyperoxia. Localization of p21(WAF/CIP1) was found in the peripheral airway cells. Hyperoxia-induced p21(WAF/CIP1) expression was then shown to be mediated through the p53 pathway, using adult p53 mutant mice. These studies demonstrated that p21(WAF/CIP1) is induced both in cells grown in culture and in neonatal and adult lung exposed to high levels of hyperoxia. Localization of p21(WAF/CIP1) expression to the peripheral airway cells suggests that p21(WAF/CIP1) may act to inhibit growth of alveoli in neonatal lung and delay repopulation of alveolar cells during hyperoxic administration.