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

Je-Oh Lim,Joong-Sun Kim,So-Won Pak,In-Chul Lee,Jong-Choon Kim,Young-Kwon Cho,Se-Jin Lee,In-Sik Shin,Woong-Il Kim

doi:10.3390/antiox10111765

Abstract

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 TNF-α, IL-6, and IL-1β, 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.

Highlights

Silica dioxide nanoparticles (SiONPs) have been extensively used in biotechnology owing to the simple production process and ability to modify their shape and size [1]
The increasing use of SiONPs has raised concerns regarding their potential toxicity in humans. This is true in an industrial setting where SiONPs can be inhaled and can be linked to serious health problems, including lung cancer, silicosis, emphysema, and chronic obstructive pulmonary disease (COPD) [2,3]
The goals of this study were to explore the anti-inflammatory effect of melatonin on SiONPs-induced pulmonary inflammation and to elucidate the underlying mechanism of this hormone by focusing on its effects on thioredoxin-interacting protein (TXNIP)/MAPKs signalling

Summary

Introduction

Silica dioxide nanoparticles (SiONPs) have been extensively used in biotechnology owing to the simple production process and ability to modify their shape and size [1]. The increasing use of SiONPs has raised concerns regarding their potential toxicity in humans. This is true in an industrial setting where SiONPs can be inhaled and can be linked to serious health problems, including lung cancer, silicosis, emphysema, and chronic obstructive pulmonary disease (COPD) [2,3]. Inhaled SiONPs induce significant pulmonary inflammation, which can result in the activation of the MAPKs [4,5,6,7]. These responses further induce the activation of AP-1, resulting in accelerated inflammatory processes [8]. SiONPs are a major component in the Asian sand dust that affects northeast Asian countries, including China, Japan and Korea, especially in the spring, and are associated with the occurrence of various pulmonary diseases across

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