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Inflammatory Response of Pulmonary Artery Smooth Muscle Cells Exposed to Oxidative and Biophysical Stress

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Abstract

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.

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Financial Support

Support was provided in part by COBRE grant P20 GM 103464-Phase 2 from the NIGMS, a component of the NIH. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of NIGMS or NIH.

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Authors and Affiliations

  1. Department of Pediatrics, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA

    Joanna Costa, Yan Zhu, Thomas Shaffer & Deepthi Alapati

  2. Center for Pediatric Lung Research, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA

    Joanna Costa, Yan Zhu, Thomas Shaffer & Deepthi Alapati

  3. Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA

    Joanna Costa, Thomas Shaffer & Deepthi Alapati

  4. Division of Neonatology, Nemours/Alfred I. duPont Hospital for Children, 1600 Rockland Road, Wilmington, DE, 19803, USA

    Deepthi Alapati

  5. Departments of Anesthesia, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA

    Timothy Cox

  6. Center for Clinical Diagnostics, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA

    Paul Fawcett

  7. Temple University School of Medicine, Philadelphia, PA, USA

    Thomas Shaffer

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  1. Joanna Costa
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Correspondence to Deepthi Alapati.

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Costa, J., Zhu, Y., Cox, T. et al. Inflammatory Response of Pulmonary Artery Smooth Muscle Cells Exposed to Oxidative and Biophysical Stress. Inflammation 41, 1250–1258 (2018). https://doi.org/10.1007/s10753-018-0772-0

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