Paracoxib Alleviates Ventilator-Induced Lung Injury Through Functional Modulation of Lung-Recruited CD11bloLy6Chi Monocytes.


Journal

Shock (Augusta, Ga.)
ISSN: 1540-0514
Titre abrégé: Shock
Pays: United States
ID NLM: 9421564

Informations de publication

Date de publication:
01 02 2021
Historique:
pubmed: 27 6 2020
medline: 14 1 2022
entrez: 27 6 2020
Statut: ppublish

Résumé

Lung-recruited Ly6Chi monocytes had been shown to be involved in ventilator-induced lung injury (VILI). Our present study aimed to investigate whether the cyclooxygenase-2 (COX-2) inhibition modulates the function of lung-recruited Ly6Chi monocytes in a mouse model of VILI. Mice were exposed to lipopolysaccharide (LPS; 20 ng) intraperitoneally prior to injurious mechanical ventilation (Vt = 30 mL/kg, PEEP = 0 cmH2O). A subgroup of mice was treated with intravenous parecoxib (30 mg/kg), a COX-2 inhibitor, 1 h prior to ventilation. Control mice received saline and were not ventilated. At the end of the experiment, blood gas analysis was performed and lung tissue was collected for histological assessment. Flow cytometry was employed to quantify the different populations of lung monocytes/macrophages and their function. Isolated Ly6Chi cells were used to measure the intracellular concentrations of reactive oxygen species (ROS) and nitric oxide (NO) by fluorescent probes, and cytokine production by cytometric bead array. Exposure to LPS and injurious ventilation was associated with severe lung histological damage, oxygenation impairment, and pulmonary edema; all of which were largely attenuated following the treatment of parecoxib. Furthermore, flow cytometry analysis revealed that parecoxib caused a reduction in the number of the lung-recruited CD11bloLy6Chi monocytes while there was no effect on tissue-resident CD64+ alveolar macrophages. In addition, the production of oxidative stress products (ROS, NO), MHC-II expression, and inflammatory cytokines in response to LPS and VILI in CD11bloLy6Chi monocytes was ameliorated by parecoxib. Parecoxib-induced alleviation of oxidative stress and inflammation in lung-recruited Ly6Chi monocytes may partly explain the beneficial action of COX-2 inhibition in VILI.

Identifiants

pubmed: 32590697
pii: 00024382-202102000-00012
doi: 10.1097/SHK.0000000000001591
doi:

Substances chimiques

Cyclooxygenase 2 Inhibitors 0
Isoxazoles 0
parecoxib 9TUW81Y3CE

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

236-243

Informations de copyright

Copyright © 2020 by the Shock Society.

Déclaration de conflit d'intérêts

The authors report no conflicts of interest.

Références

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Auteurs

Chaofeng Zhang (C)

Department of Anesthesiology, First Affiliated Hospital of USTC (Anhui Provincial Hospital), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

Shanshan Hu (S)

Institute of Clinical Pharmacology, Anhui Medical University, Hefei, China.

Graeme R Zosky (GR)

Menzies Institute for Medical Research, College of Health and Medicine, University of Tasmania, Hobart, Tasmania, Australia.
School of Medicine, College of Health and Medicine, University of Tasmania, Hobart, Tasmania, Australia.

Xin Wei (X)

Department of Anesthesiology, First Affiliated Hospital of USTC (Anhui Provincial Hospital), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

Shuhua Shu (S)

Department of Anesthesiology, First Affiliated Hospital of USTC (Anhui Provincial Hospital), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

Di Wang (D)

Department of Anesthesiology, First Affiliated Hospital of USTC (Anhui Provincial Hospital), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

Xiaoqing Chai (X)

Department of Anesthesiology, First Affiliated Hospital of USTC (Anhui Provincial Hospital), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

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