Figure 9
JNK knockout and PD98059-treated mice reduced hyperoxia-augmented, high-tidal volume (VT)-induced apoptosis of airway epithelium. The mice ventilated at a VT of 30 ml/kg with or without hyperoxia were pretreated with 1 mg/kg PD98059 for 30 minutes. Representative photomicrographs (×400) with cleaved PARP staining of the lung sections (n = 5 per group). (a) Control wild-type (WT) mice with room air (RA). (b) Control WT mice with hyperoxia. (c) WT mice ventilated at a VT of 30 ml/kg with RA. (d) WT mice ventilated at a VT of 30 ml/kg with hyperoxia. (e) JNK1-/- mice ventilated at a VT of 30 ml/kg with RA. (f) JNK1-/- mice ventilated at a VT of 30 ml/kg with hyperoxia. (g) WT mice pretreated with PD98059 and ventilated at a VT of 30 ml/kg with RA. (h) WT mice pretreated with PD98059 and ventilated at a VT of 30 ml/kg with hyperoxia. Positive staining of airway epithelia is identified by arrows. Cleaved PARP-positive cells were quantified as the average number of epithelial cells with dark brown DAB signals per bronchiole, which were counted from 10 randomly chosen bronchioles of each section (n = 5 per group). *p < 0.05 versus control, non-ventilated mice; †p < 0.05 versus ventilation in JNK1-/- or with PD98059. DAB, diaminobenzidine; ERK, extracellular signal-regulated kinase; JNK, c-Jun NH2-terminal kinase; PARP, poly(ADP-ribose)polymerase.