Melatonin Alleviates Silica Nanoparticle-Induced Lung Inflammation via Thioredoxin-Interacting Protein Downregulation

Silica dioxide nanoparticles (SiONPs) have been increasingly used in various industries; however, this has raised concerns regarding their potential toxicity. SiONPs are also a major component in the Asian sand dust that causes pulmonary diseases among the general public. Melatonin exerts some inhib...

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Autores principales: Je-Oh Lim, Se-Jin Lee, Woong-Il Kim, So-Won Pak, Jong-Choon Kim, Joong-Sun Kim, Young-Kwon Cho, In-Chul Lee, In-Sik Shin
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Publicado: MDPI AG 2021
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Acceso en línea:https://doaj.org/article/43c4868c58bb46619bd59f9d152b7ca5
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spelling oai:doaj.org-article:43c4868c58bb46619bd59f9d152b7ca52021-11-25T16:27:59ZMelatonin Alleviates Silica Nanoparticle-Induced Lung Inflammation via Thioredoxin-Interacting Protein Downregulation10.3390/antiox101117652076-3921https://doaj.org/article/43c4868c58bb46619bd59f9d152b7ca52021-11-01T00:00:00Zhttps://www.mdpi.com/2076-3921/10/11/1765https://doaj.org/toc/2076-3921Silica dioxide nanoparticles (SiONPs) have been increasingly used in various industries; however, this has raised concerns regarding their potential toxicity. SiONPs are also a major component in the Asian sand dust that causes pulmonary diseases among the general public. Melatonin exerts some inhibitory effects against lung inflammation. In this study, we explored the therapeutic properties of melatonin against lung inflammation using an SiONPs-induced lung inflammation murine model and SiONPs-stimulated H292 cells, human airway epithelial cell line, by focusing on the involvement of thioredoxin-interacting protein (TXNIP) in the modulation of the MAPKs/AP-1 axis. We induced an inflammatory response by exposing mouse lungs and the H292 cells to SiONPs and confirmed the anti-inflammatory effect of melatonin. Melatonin inhibited the expression of various inflammatory mediators, including <i>TNF-α</i>, <i>IL-6</i>, and <i>IL-1β</i>, in SiONPs-exposed mice and SiONPs-stimulated H292 cells; this inhibition contributed to a decline in inflammatory cell accumulation in the lung tissues. Furthermore, melatonin treatment decreased the expression of MAPKs and AP-1 by downregulating TXNIP, eventually decreasing the production of SiONPs-induced inflammatory mediators. Overall, these data suggest that melatonin reduces SiONPs-induced lung inflammation by downregulating the TXNIP/MAPKs/AP-1 signalling pathway, thereby supporting the use of melatonin as an effective approach to control SiONPs-induced lung inflammation.Je-Oh LimSe-Jin LeeWoong-Il KimSo-Won PakJong-Choon KimJoong-Sun KimYoung-Kwon ChoIn-Chul LeeIn-Sik ShinMDPI AGarticlemelatoninsilica dioxide nanoparticlelung inflammationhuman airway epithelial cell linethioredoxin-interacting proteinTherapeutics. PharmacologyRM1-950ENAntioxidants, Vol 10, Iss 1765, p 1765 (2021)
institution DOAJ
collection DOAJ
language EN
topic melatonin
silica dioxide nanoparticle
lung inflammation
human airway epithelial cell line
thioredoxin-interacting protein
Therapeutics. Pharmacology
RM1-950
spellingShingle melatonin
silica dioxide nanoparticle
lung inflammation
human airway epithelial cell line
thioredoxin-interacting protein
Therapeutics. Pharmacology
RM1-950
Je-Oh Lim
Se-Jin Lee
Woong-Il Kim
So-Won Pak
Jong-Choon Kim
Joong-Sun Kim
Young-Kwon Cho
In-Chul Lee
In-Sik Shin
Melatonin Alleviates Silica Nanoparticle-Induced Lung Inflammation via Thioredoxin-Interacting Protein Downregulation
description Silica dioxide nanoparticles (SiONPs) have been increasingly used in various industries; however, this has raised concerns regarding their potential toxicity. SiONPs are also a major component in the Asian sand dust that causes pulmonary diseases among the general public. Melatonin exerts some inhibitory effects against lung inflammation. In this study, we explored the therapeutic properties of melatonin against lung inflammation using an SiONPs-induced lung inflammation murine model and SiONPs-stimulated H292 cells, human airway epithelial cell line, by focusing on the involvement of thioredoxin-interacting protein (TXNIP) in the modulation of the MAPKs/AP-1 axis. We induced an inflammatory response by exposing mouse lungs and the H292 cells to SiONPs and confirmed the anti-inflammatory effect of melatonin. Melatonin inhibited the expression of various inflammatory mediators, including <i>TNF-α</i>, <i>IL-6</i>, and <i>IL-1β</i>, in SiONPs-exposed mice and SiONPs-stimulated H292 cells; this inhibition contributed to a decline in inflammatory cell accumulation in the lung tissues. Furthermore, melatonin treatment decreased the expression of MAPKs and AP-1 by downregulating TXNIP, eventually decreasing the production of SiONPs-induced inflammatory mediators. Overall, these data suggest that melatonin reduces SiONPs-induced lung inflammation by downregulating the TXNIP/MAPKs/AP-1 signalling pathway, thereby supporting the use of melatonin as an effective approach to control SiONPs-induced lung inflammation.
format article
author Je-Oh Lim
Se-Jin Lee
Woong-Il Kim
So-Won Pak
Jong-Choon Kim
Joong-Sun Kim
Young-Kwon Cho
In-Chul Lee
In-Sik Shin
author_facet Je-Oh Lim
Se-Jin Lee
Woong-Il Kim
So-Won Pak
Jong-Choon Kim
Joong-Sun Kim
Young-Kwon Cho
In-Chul Lee
In-Sik Shin
author_sort Je-Oh Lim
title Melatonin Alleviates Silica Nanoparticle-Induced Lung Inflammation via Thioredoxin-Interacting Protein Downregulation
title_short Melatonin Alleviates Silica Nanoparticle-Induced Lung Inflammation via Thioredoxin-Interacting Protein Downregulation
title_full Melatonin Alleviates Silica Nanoparticle-Induced Lung Inflammation via Thioredoxin-Interacting Protein Downregulation
title_fullStr Melatonin Alleviates Silica Nanoparticle-Induced Lung Inflammation via Thioredoxin-Interacting Protein Downregulation
title_full_unstemmed Melatonin Alleviates Silica Nanoparticle-Induced Lung Inflammation via Thioredoxin-Interacting Protein Downregulation
title_sort melatonin alleviates silica nanoparticle-induced lung inflammation via thioredoxin-interacting protein downregulation
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/43c4868c58bb46619bd59f9d152b7ca5
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