Figure 3

Blockade of cAMP-dependent CFTR channels via JAK3 activation exacerbates acute lung injury in response to H5N1 HA challenge. Histopathologic examination via hematoxylin and eosin (H&E) staining was performed on the lung sections of JAK3^+/− and JAK3^+/+ mice. (A) JAK3^+/+ mice treated with saline; (B) with HA alone at 1 mg/kg or (G) 0.5 mg/kg; (C) HA (1 mg/kg) with either forskolin (FSK, 10 mg/kg) or (D) JAK3 inhibitor VI (JAK3inh, 0.15 mg/kg); (F) glibenclamide pretreatment (Gli, 10 mg/kg) alone or (H) HA (0.5 mg/kg) with glibenclamide pretreatment. (E) JAK3^+/− mice treated with HA (1 mg/kg). Scale bars = 100 µm. h: high (1 mg/kg); L: low (0.5 mg/kg). (I) The lung injury score is assessed. The data are expressed as the mean ± SEM, with n = 5 per group. *p < 0.05, versus saline control; ^#p < 0.05 versus the HA(h)-challenged JAK3^+/+ group. (J) Immunofluorescent staining was performed to examine CFTR expression in JAK3^+/+mice treated with saline or (K) HA (1 mg/kg) for 4 h. Scale bars = 40 µm. The arrows indicate positively stained cells. (L) Western blot analysis was performed to determine the level of CFTR expression. *p < 0.05, versus saline control, c: control.