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Selective CB(2) Receptor Agonist, HU-308, Reduces Systemic Inflammation in Endotoxin Model of Pneumonia-Induced Acute Lung Injury
Acute respiratory distress syndrome (ARDS) and sepsis are risk factors contributing to mortality in patients with pneumonia. In ARDS, also termed acute lung injury (ALI), pulmonary immune responses lead to excessive pro-inflammatory cytokine release and aberrant alveolar neutrophil infiltration. Sys...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9779896/ https://www.ncbi.nlm.nih.gov/pubmed/36555499 http://dx.doi.org/10.3390/ijms232415857 |
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author | Hall, Stefan Faridi, Sufyan Trivedi, Purvi Sultana, Saki Ray, Bithika Myers, Tanya Euodia, Irene Vlatten, David Castonguay, Mathieu Zhou, Juan Kelly, Melanie Lehmann, Christian |
author_facet | Hall, Stefan Faridi, Sufyan Trivedi, Purvi Sultana, Saki Ray, Bithika Myers, Tanya Euodia, Irene Vlatten, David Castonguay, Mathieu Zhou, Juan Kelly, Melanie Lehmann, Christian |
author_sort | Hall, Stefan |
collection | PubMed |
description | Acute respiratory distress syndrome (ARDS) and sepsis are risk factors contributing to mortality in patients with pneumonia. In ARDS, also termed acute lung injury (ALI), pulmonary immune responses lead to excessive pro-inflammatory cytokine release and aberrant alveolar neutrophil infiltration. Systemic spread of cytokines is associated with systemic complications including sepsis, multi-organ failure, and death. Thus, dampening pro-inflammatory cytokine release is a viable strategy to improve outcome. Activation of cannabinoid type II receptor (CB(2)) has been shown to reduce cytokine release in various in vivo and in vitro studies. Herein, we investigated the effect of HU-308, a specific CB(2) agonist, on systemic and pulmonary inflammation in a model of pneumonia-induced ALI. C57Bl/6 mice received intranasal endotoxin or saline, followed by intravenous HU-308, dexamethasone, or vehicle. ALI was scored by histology and plasma levels of select inflammatory mediators were assessed by Luminex assay. Intravital microscopy (IVM) was performed to assess leukocyte adhesion and capillary perfusion in intestinal and pulmonary microcirculation. HU-308 and dexamethasone attenuated LPS-induced cytokine release and intestinal microcirculatory impairment. HU-308 modestly reduced ALI score, while dexamethasone abolished it. These results suggest administration of HU-308 can reduce systemic inflammation without suppressing pulmonary immune response in pneumonia-induced ALI and systemic inflammation. |
format | Online Article Text |
id | pubmed-9779896 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-97798962022-12-23 Selective CB(2) Receptor Agonist, HU-308, Reduces Systemic Inflammation in Endotoxin Model of Pneumonia-Induced Acute Lung Injury Hall, Stefan Faridi, Sufyan Trivedi, Purvi Sultana, Saki Ray, Bithika Myers, Tanya Euodia, Irene Vlatten, David Castonguay, Mathieu Zhou, Juan Kelly, Melanie Lehmann, Christian Int J Mol Sci Article Acute respiratory distress syndrome (ARDS) and sepsis are risk factors contributing to mortality in patients with pneumonia. In ARDS, also termed acute lung injury (ALI), pulmonary immune responses lead to excessive pro-inflammatory cytokine release and aberrant alveolar neutrophil infiltration. Systemic spread of cytokines is associated with systemic complications including sepsis, multi-organ failure, and death. Thus, dampening pro-inflammatory cytokine release is a viable strategy to improve outcome. Activation of cannabinoid type II receptor (CB(2)) has been shown to reduce cytokine release in various in vivo and in vitro studies. Herein, we investigated the effect of HU-308, a specific CB(2) agonist, on systemic and pulmonary inflammation in a model of pneumonia-induced ALI. C57Bl/6 mice received intranasal endotoxin or saline, followed by intravenous HU-308, dexamethasone, or vehicle. ALI was scored by histology and plasma levels of select inflammatory mediators were assessed by Luminex assay. Intravital microscopy (IVM) was performed to assess leukocyte adhesion and capillary perfusion in intestinal and pulmonary microcirculation. HU-308 and dexamethasone attenuated LPS-induced cytokine release and intestinal microcirculatory impairment. HU-308 modestly reduced ALI score, while dexamethasone abolished it. These results suggest administration of HU-308 can reduce systemic inflammation without suppressing pulmonary immune response in pneumonia-induced ALI and systemic inflammation. MDPI 2022-12-13 /pmc/articles/PMC9779896/ /pubmed/36555499 http://dx.doi.org/10.3390/ijms232415857 Text en © 2022 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 Hall, Stefan Faridi, Sufyan Trivedi, Purvi Sultana, Saki Ray, Bithika Myers, Tanya Euodia, Irene Vlatten, David Castonguay, Mathieu Zhou, Juan Kelly, Melanie Lehmann, Christian Selective CB(2) Receptor Agonist, HU-308, Reduces Systemic Inflammation in Endotoxin Model of Pneumonia-Induced Acute Lung Injury |
title | Selective CB(2) Receptor Agonist, HU-308, Reduces Systemic Inflammation in Endotoxin Model of Pneumonia-Induced Acute Lung Injury |
title_full | Selective CB(2) Receptor Agonist, HU-308, Reduces Systemic Inflammation in Endotoxin Model of Pneumonia-Induced Acute Lung Injury |
title_fullStr | Selective CB(2) Receptor Agonist, HU-308, Reduces Systemic Inflammation in Endotoxin Model of Pneumonia-Induced Acute Lung Injury |
title_full_unstemmed | Selective CB(2) Receptor Agonist, HU-308, Reduces Systemic Inflammation in Endotoxin Model of Pneumonia-Induced Acute Lung Injury |
title_short | Selective CB(2) Receptor Agonist, HU-308, Reduces Systemic Inflammation in Endotoxin Model of Pneumonia-Induced Acute Lung Injury |
title_sort | selective cb(2) receptor agonist, hu-308, reduces systemic inflammation in endotoxin model of pneumonia-induced acute lung injury |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9779896/ https://www.ncbi.nlm.nih.gov/pubmed/36555499 http://dx.doi.org/10.3390/ijms232415857 |
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