Dexamethasone inhibits respiratory syncytial virus-driven mucus production while increasing viral replication without altering antiviral interferon signaling.

Respiratory syncytial virus (RSV) infection can cause mucus overproduction and bronchiolitis in infants leading to severe disease and hospitalization. As a therapeutic strategy, immune modulatory agents may help prevent RSV-driven immune responses that cause severe airway disease. We developed a high throughput screen to identify compounds that reduced RSV-driven mucin 5AC (Muc5AC) expression and identified dexamethasone.

Pleiotropic effects of statins in distal human pulmonary artery smooth muscle cells.

Background: Recent clinical data suggest statins have transient but significant effects in patients with pulmonary arterial hypertension. In this study we explored the molecular effects of statins on distal human pulmonary artery smooth muscle cells (PASMCs) and their relevance to proliferation and apoptosis in pulmonary arterial hypertension.

Methods: Primary distal human PASMCs from patients and controls were treated with lipophilic (simvastatin, atorvastatin, mevastatin and fluvastatin), lipophobic (pravastatin) and nitric-oxide releasing statins and studied in terms of their DNA synthesis, proliferation, apoptosis, matrix metalloproteinase-9 and endothelin-1 release.

Phosphodiesterase type 4 expression and anti-proliferative effects in human pulmonary artery smooth muscle cells.

Background: Pulmonary arterial hypertension is a proliferative vascular disease, characterized by aberrant regulation of smooth muscle cell proliferation and apoptosis in distal pulmonary arteries. Prostacyclin (PGI2) analogues have anti-proliferative effects on distal human pulmonary artery smooth muscle cells (PASMCs), which are dependent on intracellular cAMP stimulation. We therefore sought to investigate the involvement of the main cAMP-specific enzymes, phosphodiesterase type 4 (PDE4), responsible for cAMP hydrolysis.

Antiproliferative effects of phosphodiesterase type 5 inhibition in human pulmonary artery cells.

Rationale: Phosphodiesterase Type 5 (PDE5) inhibition represents a novel strategy for the treatment of pulmonary hypertension.

Objectives: Our aim was to establish the distribution of PDE5 in the pulmonary vasculature and effects of PDE5 inhibition on pulmonary artery smooth muscle cells (PASMCs).

Methods And Measurements: PDE5 expression was examined by immunohistochemistry and Western blotting, in both normal and hypertensive lung tissues.