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Respiratory Research
Published in: Respiratory Research 1/2020

Open Access 01-12-2020 | Acute Respiratory Distress-Syndrome | Research

Melatonin receptor agonist protects against acute lung injury induced by ventilator through up-regulation of IL-10 production

Authors: Geng-Chin Wu, Chung-Kan Peng, Wen-I Liao, Hsin-Ping Pao, Kun-Lun Huang, Shi-Jye Chu

Published in: Respiratory Research | Issue 1/2020

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Abstract

Background

It is well known that ventilation with high volume or pressure may damage healthy lungs or worsen injured lungs. Melatonin has been reported to be effective in animal models of acute lung injury. Melatonin exerts its beneficial effects by acting as a direct antioxidant and via melatonin receptor activation. However, it is not clear whether melatonin receptor agonist has a protective effect in ventilator-induced lung injury (VILI). Therefore, in this study, we determined whether ramelteon (a melatonin receptor agonist) can attenuate VILI and explore the possible mechanism for protection.

Methods

VILI was induced by high tidal volume ventilation in a rat model. The rats were randomly allotted into the following groups: control, control+melatonin, control+ramelteon, control+luzindole, VILI, VILI+luzindole, VILI + melatonin, VILI + melatonin + luzindole (melatonin receptor antagonist), VILI + ramelteon, and VILI + ramelteon + luzindole (n = 6 per group). The role of interleukin-10 (IL-10) in the melatonin- or ramelteon-mediated protection against VILI was also investigated.

Results

Ramelteon treatment markedly reduced lung edema, serum malondialdehyde levels, the concentration of inflammatory cytokines in bronchoalveolar lavage fluid (BALF), NF-κB activation, iNOS levels, and apoptosis in the lung tissue. Additionally, ramelteon treatment significantly increased heat shock protein 70 expression in the lung tissue and IL-10 levels in BALF. The protective effect of ramelteon was mitigated by the administration of luzindole or an anti-IL-10 antibody.

Conclusions

Our results suggest that a melatonin receptor agonist has a protective effect against VILI, and its protective mechanism is based on the upregulation of IL-10 production.
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Metadata
Title
Melatonin receptor agonist protects against acute lung injury induced by ventilator through up-regulation of IL-10 production
Authors
Geng-Chin Wu
Chung-Kan Peng
Wen-I Liao
Hsin-Ping Pao
Kun-Lun Huang
Shi-Jye Chu
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2020
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/s12931-020-1325-2

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