Cystic fibrosis and normal human airway epithelial cell response to influenza a viral infection.

Viral infections produce severe respiratory morbidity in children with cystic fibrosis (CF). CF cells are more susceptible to virus in part because of impaired airway epithelial activation of signal transducer and activator of transcription 1 (Stat1). As Stat1 is a fundamental regulator of antiviral defenses, we hypothesized that there may be multiple alterations in the antiviral defense of CF epithelium compared with normal (NL).

Increased arginase II and decreased NO synthesis in endothelial cells of patients with pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH), a fatal disease of unknown etiology characterized by impaired regulation of pulmonary hemodynamics and vascular growth, is associated with low levels of pulmonary nitric oxide (NO). Based upon its critical role in mediating vasodilation and cell growth, decrease of NO has been implicated in the pathogenesis of PAH. We evaluated mechanisms for low NO and pulmonary hypertension, including NO synthases (NOS) and factors regulating NOS activity, i.

Impaired innate host defense causes susceptibility to respiratory virus infections in cystic fibrosis.

Viral infection is the primary cause of respiratory morbidity in cystic fibrosis (CF) infants. Here, we identify that host factors allow increased virus replication and cytokine production, providing a mechanism for understanding the severity of virus disease in CF. Increased virus is due to lack of nitric oxide synthase 2 (NOS2) and 2', 5' oligoadenylate synthetase (OAS) 1 induction in response to virus or IFNgamma.