Submitted on March 3, 2006
Accepted on September 29, 2006
Cyclical Stretch Induces PlGF expression in Bronchial Epithelial Cells via Nitric Oxide Release
Kamal Abdul Mohammed1*, Najmunnisa Nasreen1, Robert S. Tepper2, and Veena B Antony1
1 Pulmonary Medicine, University of Florida, Gainesville, Florida, United States
2 Section of Pediatric Pulmonology, Rm. 2750, James Whitcomb Riley Hospital for Children, Indianapolis, Indiana, United States
* To whom correspondence should be addressed. E-mail: mkamal{at}medicine.ufl.edu.
Mechanical strain of lung tissue is an important stimulus for the production of growth factors that are critical for lung growth and development. However, excessive mechanical strain, as may occur during mechanical ventilation, may produce an increase in growth factors that may contribute to lung injury. We hypothesized that mechanical strain of primary bronchial airway epithelial cells (BAEpC) induced the production of placental growth factor (PlGF), a member of the VEGF family. BAEpC were cultured on a deformable silico-elastic membrane and exposed to different magnitudes of stretch. Stretch induced PlGF and nitric oxide (NO) production that increased with increasing magnitude of stretch. Stretch also induced PlGF and iNOS gene expression. The stretch induced PlGF production and NO synthesis was attenuated by PD98059, a specific mitogen-activated protein kinase kinase 1 and 2 inhibitor. Inhibition of NO generation by N-nitro-L-arginine (L-NAME), L-NG-monomethyl Arginine citrate (L-NMMA) or scavenging NO by carboxy-PTIO prevented stretch mediated erk1/2 activation. In addition, in unstretched BAEpC exogenous NO enhanced erk1/erk2 activation. Our data suggests that mechanical stretch of BAEpC induces iNOS expression and induces PlGF release in an erk1/2 activation dependent manner.
