CNP-miR146a Decreases Inflammation in Murine Acute Infectious Lung Injury
Alyssa E. Vaughn,
Tanner Lehmann,
Christina Sul,
Alison M. Wallbank,
Bailey D. Lyttle,
James Bardill,
Nana Burns,
Anisha Apte,
Eva S. Nozik,
Bradford Smith,
Christine U. Vohwinkel,
Carlos Zgheib,
Kenneth W. Liechty
Affiliations
Alyssa E. Vaughn
Laboratory for Fetal and Regenerative Biology, Department of Surgery, University of Colorado Denver and Children’s Hospital Colorado, Aurora, CO 80045, USA
Tanner Lehmann
Laboratory for Fetal and Regenerative Biology, Department of Surgery, University of Colorado Denver and Children’s Hospital Colorado, Aurora, CO 80045, USA
Christina Sul
Cardiovascular Pulmonary Research Laboratories and Pediatric Critical Care Medicine, Department of Pediatrics, University of Colorado Denver, Aurora, CO 80045, USA
Alison M. Wallbank
Department of Bioengineering, University of Colorado Denver, Aurora, CO 80045, USA
Bailey D. Lyttle
Laboratory for Fetal and Regenerative Biology, Department of Surgery, University of Colorado Denver and Children’s Hospital Colorado, Aurora, CO 80045, USA
James Bardill
Laboratory for Fetal and Regenerative Biology, Department of Surgery, University of Colorado Denver and Children’s Hospital Colorado, Aurora, CO 80045, USA
Nana Burns
Cardiovascular Pulmonary Research Laboratories and Pediatric Critical Care Medicine, Department of Pediatrics, University of Colorado Denver, Aurora, CO 80045, USA
Anisha Apte
Laboratory for Fetal and Regenerative Biology, Department of Surgery, University of Arizona Tucson College of Medicine and Banner Children’s at Diamond Children’s Medical Center, Tucson, AZ 85721, USA
Eva S. Nozik
Cardiovascular Pulmonary Research Laboratories and Pediatric Critical Care Medicine, Department of Pediatrics, University of Colorado Denver, Aurora, CO 80045, USA
Bradford Smith
Department of Bioengineering, University of Colorado Denver, Aurora, CO 80045, USA
Christine U. Vohwinkel
Cardiovascular Pulmonary Research Laboratories and Pediatric Critical Care Medicine, Department of Pediatrics, University of Colorado Denver, Aurora, CO 80045, USA
Carlos Zgheib
Laboratory for Fetal and Regenerative Biology, Department of Surgery, University of Arizona Tucson College of Medicine and Banner Children’s at Diamond Children’s Medical Center, Tucson, AZ 85721, USA
Kenneth W. Liechty
Laboratory for Fetal and Regenerative Biology, Department of Surgery, University of Arizona Tucson College of Medicine and Banner Children’s at Diamond Children’s Medical Center, Tucson, AZ 85721, USA
Acute respiratory distress syndrome (ARDS) has approximately 40% in-hospital mortality, and treatment is limited to supportive care. Pneumonia is the underlying etiology in many cases with unrestrained inflammation central to the pathophysiology. We have previously shown that CNP-miR146a, a radical scavenging cerium oxide nanoparticle (CNP) conjugated to the anti-inflammatory microRNA(miR)-146a, reduces bleomycin- and endotoxin-induced acute lung injury (ALI) by decreasing inflammation. We therefore hypothesized that CNP-miR146a would decrease inflammation in murine infectious ALI. Mice were injured with intratracheal (IT) MRSA or saline followed by treatment with IT CNP-miR146a or saline control. Twenty-four hours post-infection, bronchoalveolar lavage fluid (BALF) and whole lungs were analyzed for various markers of inflammation. Compared to controls, MRSA infection significantly increased proinflammatory gene expression (IL-6, IL-8, TNFα, IL-1β; p p p = 0.03). CNP-miR146a treatment significantly decreased proinflammatory gene expression (IL-6, IL-8, TNFα, IL-1β; p p p = 0.01). CNP-miR146a decreases inflammation and improves alveolar–capillary barrier integrity in the MRSA-infected lung and has significant promise as a potential therapeutic for ARDS.
