CNP-miR146a Decreases Inflammation in Murine Acute Infectious Lung Injury

• Published in: Pharmaceutics 2023-08, Vol.15 (9), p.2210
• Main Authors: Vaughn, Alyssa E, Lehmann, Tanner, Sul, Christina, Wallbank, Alison M, Lyttle, Bailey D, Bardill, James, Burns, Nana, Apte, Anisha, Nozik, Eva S, Smith, Bradford, Vohwinkel, Christine U, Zgheib, Carlos, Liechty, Kenneth W
• Format: Article
• Language: English
• Subjects: acute respiratory distress syndrome; B cells; Bacterial pneumonia; bioactive nanoparticle therapeutic; Cerium; cerium oxide nanoparticles (CNP); Cytokines; Gene expression; Genes; Health aspects; infectious lung injury model; Inflammation; Kinases; Laboratory animals; Lavage; Lungs; Methicillin; microRNA-146a (miR146a); MicroRNAs; Nitric oxide; Ostomy; Oxidative stress; Pneumonia; Proteins; Staphylococcus aureus; Staphylococcus aureus infections; Staphylococcus infections
• ISSN: 1999-4923; 1999-4923
• DOI: 10.3390/pharmaceutics15092210

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; < 0.05), BALF proinflammatory cytokines (IL-6, IL-8, TNFα, IL-1β; < 0.01), and inflammatory cell infiltrate ( = 0.03). CNP-miR146a treatment significantly decreased proinflammatory gene expression (IL-6, IL-8, TNFα, IL-1β; < 0.05), bronchoalveolar proinflammatory protein leak (IL-6, IL-8, TNFα; < 0.05), and inflammatory infiltrate ( = 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.