title: Nitric Oxide and Cellular Maturity Are Key Components of Pro-Inflammatory Cytokine-Induced Apoptosis of Human Fetal Lung Epithelial Cells.
abstract: Inflammation is a major contributor to the pathogenesis of bronchopulmonary dysplasia (BPD). BPD is associated with prematurity of birth, sepsis, with increased production of both cytokines and nitric oxide, and with the shedding of bronchial epithelial cells. The pathological mechanisms involved in this disease remain unclear, in particular the role that epithelial maturity plays. The effects of pro-inflammatory cytokines upon immature and mature cells are examined within this study, using primary culture of human lung epithelial cells. Pro-inflammatory cytokines increase inducible nitric oxide synthase (iNOS) expression and raise NO production, irrespective of cellular maturity. Pre-incubation with 1400W, a specific iNOS inhibitor, abrogated pro-inflammatory cytokine-induced NO generation and apoptosis. However, immature fetal lung epithelial cells were uniquely sensitive to cellular injury in response to cytokine exposure. These observations suggest that pro-inflammatory cytokines, which are present within BPD, may cause apoptosis of lung epithelial cellsviade novo generation of NO. Furthermore, the prematurity of lung epithelial cells may be a factor in free radical mediated pulmonary damage.
authors.affiliation: The Children's Hospital of Philadelphia, Division of Neonatology, Philadelphia, PA 19104, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Posencheg
authors.affiliation: Rutgers, The State University of New Jersey, Department of Pharmacology & Toxicology, Busch Campus, Piscataway, NJ 08854, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Gow
authors.affiliation: The Children's Hospital of Philadelphia, Division of Neonatology, Philadelphia, PA 19104, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.affiliation: The Children's Hospital of Philadelphia, Division of Neonatology, Philadelphia, PA 19104, USA.
authors.forename: Linda W
authors.initials: LW
authors.lastname: Gonzales
authors.affiliation: Rutgers, The State University of New Jersey, Department of Pharmacology & Toxicology, Busch Campus, Piscataway, NJ 08854, USA.
authors.forename: Changjiang
authors.initials: C
authors.lastname: Guo
keywords: apoptosis; caspase-3; iNOS; maturity; nitric oxide; type II cell