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CNP-miR146a Decreases Inflammation in Murine Acute Infectious Lung Injury
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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10535276/ https://www.ncbi.nlm.nih.gov/pubmed/37765178 http://dx.doi.org/10.3390/pharmaceutics15092210 |
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author | 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. |
author_facet | 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. |
author_sort | Vaughn, Alyssa E. |
collection | PubMed |
description | 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 < 0.05), BALF proinflammatory cytokines (IL-6, IL-8, TNFα, IL-1β; p < 0.01), and inflammatory cell infiltrate (p = 0.03). CNP-miR146a treatment significantly decreased proinflammatory gene expression (IL-6, IL-8, TNFα, IL-1β; p < 0.05), bronchoalveolar proinflammatory protein leak (IL-6, IL-8, TNFα; p < 0.05), and inflammatory infiltrate (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. |
format | Online Article Text |
id | pubmed-10535276 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-105352762023-09-29 CNP-miR146a Decreases Inflammation in Murine Acute Infectious Lung Injury 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. Pharmaceutics Article 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 < 0.05), BALF proinflammatory cytokines (IL-6, IL-8, TNFα, IL-1β; p < 0.01), and inflammatory cell infiltrate (p = 0.03). CNP-miR146a treatment significantly decreased proinflammatory gene expression (IL-6, IL-8, TNFα, IL-1β; p < 0.05), bronchoalveolar proinflammatory protein leak (IL-6, IL-8, TNFα; p < 0.05), and inflammatory infiltrate (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. MDPI 2023-08-26 /pmc/articles/PMC10535276/ /pubmed/37765178 http://dx.doi.org/10.3390/pharmaceutics15092210 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article 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. CNP-miR146a Decreases Inflammation in Murine Acute Infectious Lung Injury |
title | CNP-miR146a Decreases Inflammation in Murine Acute Infectious Lung Injury |
title_full | CNP-miR146a Decreases Inflammation in Murine Acute Infectious Lung Injury |
title_fullStr | CNP-miR146a Decreases Inflammation in Murine Acute Infectious Lung Injury |
title_full_unstemmed | CNP-miR146a Decreases Inflammation in Murine Acute Infectious Lung Injury |
title_short | CNP-miR146a Decreases Inflammation in Murine Acute Infectious Lung Injury |
title_sort | cnp-mir146a decreases inflammation in murine acute infectious lung injury |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10535276/ https://www.ncbi.nlm.nih.gov/pubmed/37765178 http://dx.doi.org/10.3390/pharmaceutics15092210 |
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