Inflammatory Response of Pulmonary Artery Smooth Muscle Cells Exposed to Oxidative and Biophysical Stress
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ORIGINAL ARTICLE
Inflammatory Response of Pulmonary Artery Smooth Muscle Cells Exposed to Oxidative and Biophysical Stress Joanna Costa,1,2,3 Yan Zhu,1,2 Timothy Cox,5 Paul Fawcett,6 Thomas Shaffer,1,2,3,7 and Deepthi Alapati 1,2,3,4,8
Pulmonary hypertension in the neonate requires treatment with oxygen and positive pressure ventilation, both known to induce lung injury. The direct response of pulmonary artery smooth muscle cells, the most abundant cells in the artery wall, to the stress of positive pressure and hyperoxia has not been previously studied. Pulmonary artery smooth muscle cells were cultured in temperature- and pressure-controlled air-tight chambers under conditions of positive pressure or hyperoxia for 24 h. Control cells were cultured in room air under atmospheric pressure. After the exposure period, culture medium was collected and samples were analyzed by ELISA, Human Cytokine 25-Plex Panel using a Luminex 200 analyzer and Western blot. Secretion of various inflammatory mediators, specifically IL-6, IL-8, IL-2R, MIP-1β, MCP-1, IP-10, IL-7, IL-1RA, and IFN-α, was higher in the positive pressure and hyperoxia groups compared with control. The level of cyclin D1 was decreased in the hyperoxia and positive pressure group compared with control. Levels of fibronectin and α-smooth muscle actin were not different among the groups. Pulmonary artery smooth muscle cells directly produce multiple inflammatory mediators in response to oxidative and biophysical stress in vitro, which may be part of a cascade that leads to the vascular and perivascular changes in pulmonary hypertension.
Abstract—
KEY WORDS: hyperoxia; inflammation; positive pressure; pulmonary hypertension.
INTRODUCTION 1
Department of Pediatrics, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA 2 Center for Pediatric Lung Research, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA 3 Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA 4 Division of Neonatology, Nemours/Alfred I. duPont Hospital for Children, 1600 Rockland Road, Wilmington, DE 19803, USA 5 Departments of Anesthesia, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA 6 Center for Clinical Diagnostics, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA 7 Temple University School of Medicine, Philadelphia, PA, USA 8 To whom correspondence should be addressed at Division of Neonatology, Nemours/Alfred I. duPont Hospital for Children, 1600 Rockland Road, Wilmington, DE 19803, USA. E-mail: [email protected]
Pulmonary hypertension (PH) occurs in a broad spectrum of clinical conditions in both children and adults. It is a serious disease in the neonate with multiple forms, including persistent pulmonary hypertension of the newborn in term infants and as a late complication of bronchopulmonary dysplasia (BPD) in preterm infants [1, 2]. In spite of recent advances in neonatal care, PH continues to be a major problem associated with increased morbidity and mortality. It is a complic
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