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NF‑κB inhibitor DHMEQ inhibits titanium dioxide nanoparticle‑induced interleukin‑1β production: Inhibition of the PM2.5‑induced inflammation model

PM2.5 is a particle with a diameter

Journal Title: Molecular medicine reports December 2018, Vol.18(6), pp.5279-5285
Main Author: Fukatsu, Hitomi
Other Authors: Koide, Naoki , Tada-Oikawa, Saeko , Izuoka, Kiyora , Ikegami, Akihiko , Ichihara, Sahoko , Ukaji, Tamami , Morita, Naoko , Naiki, Yoshikazu , Komatsu, Takayuki , Umezawa, Kazuo
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1791-3004 ; PMID: 30320338 Version:1 ; DOI: 10.3892/mmr.2018.9533
Link: http://pubmed.gov/30320338
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recordid: medline30320338
title: NF‑κB inhibitor DHMEQ inhibits titanium dioxide nanoparticle‑induced interleukin‑1β production: Inhibition of the PM2.5‑induced inflammation model
format: Article
creator:
  • Fukatsu, Hitomi
  • Koide, Naoki
  • Tada-Oikawa, Saeko
  • Izuoka, Kiyora
  • Ikegami, Akihiko
  • Ichihara, Sahoko
  • Ukaji, Tamami
  • Morita, Naoko
  • Naiki, Yoshikazu
  • Komatsu, Takayuki
  • Umezawa, Kazuo
subjects:
  • Nanoparticles
  • Titanium
  • Benzamides -- Pharmacology
  • Cyclohexanones -- Pharmacology
  • Interleukin-1beta -- Biosynthesis
  • Nf-Kappa B -- Antagonists & Inhibitors
ispartof: Molecular medicine reports, December 2018, Vol.18(6), pp.5279-5285
description: PM2.5 is a particle with a diameter
language: eng
source:
identifier: E-ISSN: 1791-3004 ; PMID: 30320338 Version:1 ; DOI: 10.3892/mmr.2018.9533
fulltext: fulltext
issn:
  • 17913004
  • 1791-3004
url: Link


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titleNF‑κB inhibitor DHMEQ inhibits titanium dioxide nanoparticle‑induced interleukin‑1β production: Inhibition of the PM2.5‑induced inflammation model
creatorFukatsu, Hitomi ; Koide, Naoki ; Tada-Oikawa, Saeko ; Izuoka, Kiyora ; Ikegami, Akihiko ; Ichihara, Sahoko ; Ukaji, Tamami ; Morita, Naoko ; Naiki, Yoshikazu ; Komatsu, Takayuki ; Umezawa, Kazuo
ispartofMolecular medicine reports, December 2018, Vol.18(6), pp.5279-5285
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subjectNanoparticles ; Titanium ; Benzamides -- Pharmacology ; Cyclohexanones -- Pharmacology ; Interleukin-1beta -- Biosynthesis ; Nf-Kappa B -- Antagonists & Inhibitors
descriptionPM2.5 is a particle with a diameter <2.5 µm that is often involved in air pollution. Nanoparticles <100 nm are thought to invade the trachea and lungs to cause inflammation, possibly through the activation of macrophages. On the other hand, titanium dioxide (TiO2) particles can be used in models of nano‑micro‑sized particles, as one can prepare the particles with such sizes. TiO2 particles are classified into Rutile, Anatase, and Brookite types by their crystal structure. Among them, Anatase‑type TiO2 particles with a primary diameter of 50 nm (A50) were reported to induce interleukin (IL)‑1β production and secretion effectively in phorbol 12‑myristate 13‑acetate‑treated human monocytic leukemia THP‑1 cells (THP‑1 macrophages). We previously designed and synthesized dehydroxymethyl‑epoxyqinomicin (DHMEQ) as an inhibitor of NF‑κB. The present study investigated whether the NF‑κB inhibitor DHMEQ inhibits TiO2 nanoparticle‑induced IL‑1β production in THP‑1 macrophages, and determined the mechanism. As a result, DHMEQ inhibited A50‑induced IL‑1β secretion in ELISA assays at nontoxic concentrations. It decreased the expression of IL‑1β mRNA, which was dependent on NF‑κB. Although NLR family pyrin domain containing 3 (NLRP3)‑inflammasome‑caspase‑1 activation is required for the maturation of IL‑1β, and DHMEQ reduced the NLRP3 mRNA expression and caspase‑1 activity; a caspase‑1 inhibitor did not influence the A50‑induced IL‑1β production. Therefore, it is likely that inhibition of pro‑IL‑1β expression by DHMEQ may be sufficient to inhibit mature IL‑1β production. Thus, DHMEQ may be useful for the amelioration of inflammation in the trachea and lungs caused by inhalation of PM2.5.
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titleNF‑κB inhibitor DHMEQ inhibits titanium dioxide nanoparticle‑induced interleukin‑1β production: Inhibition of the PM2.5‑induced inflammation model
descriptionPM2.5 is a particle with a diameter <2.5 µm that is often involved in air pollution. Nanoparticles <100 nm are thought to invade the trachea and lungs to cause inflammation, possibly through the activation of macrophages. On the other hand, titanium dioxide (TiO2) particles can be used in models of nano‑micro‑sized particles, as one can prepare the particles with such sizes. TiO2 particles are classified into Rutile, Anatase, and Brookite types by their crystal structure. Among them, Anatase‑type TiO2 particles with a primary diameter of 50 nm (A50) were reported to induce interleukin (IL)‑1β production and secretion effectively in phorbol 12‑myristate 13‑acetate‑treated human monocytic leukemia THP‑1 cells (THP‑1 macrophages). We previously designed and synthesized dehydroxymethyl‑epoxyqinomicin (DHMEQ) as an inhibitor of NF‑κB. The present study investigated whether the NF‑κB inhibitor DHMEQ inhibits TiO2 nanoparticle‑induced IL‑1β production in THP‑1 macrophages, and determined the mechanism. As a result, DHMEQ inhibited A50‑induced IL‑1β secretion in ELISA assays at nontoxic concentrations. It decreased the expression of IL‑1β mRNA, which was dependent on NF‑κB. Although NLR family pyrin domain containing 3 (NLRP3)‑inflammasome‑caspase‑1 activation is required for the maturation of IL‑1β, and DHMEQ reduced the NLRP3 mRNA expression and caspase‑1 activity; a caspase‑1 inhibitor did not influence the A50‑induced IL‑1β production. Therefore, it is likely that inhibition of pro‑IL‑1β expression by DHMEQ may be sufficient to inhibit mature IL‑1β production. Thus, DHMEQ may be useful for the amelioration of inflammation in the trachea and lungs caused by inhalation of PM2.5.
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titleNF‑κB inhibitor DHMEQ inhibits titanium dioxide nanoparticle‑induced interleukin‑1β production: Inhibition of the PM2.5‑induced inflammation model
authorFukatsu, Hitomi ; Koide, Naoki ; Tada-Oikawa, Saeko ; Izuoka, Kiyora ; Ikegami, Akihiko ; Ichihara, Sahoko ; Ukaji, Tamami ; Morita, Naoko ; Naiki, Yoshikazu ; Komatsu, Takayuki ; Umezawa, Kazuo
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abstractPM2.5 is a particle with a diameter <2.5 µm that is often involved in air pollution. Nanoparticles <100 nm are thought to invade the trachea and lungs to cause inflammation, possibly through the activation of macrophages. On the other hand, titanium dioxide (TiO2) particles can be used in models of nano‑micro‑sized particles, as one can prepare the particles with such sizes. TiO2 particles are classified into Rutile, Anatase, and Brookite types by their crystal structure. Among them, Anatase‑type TiO2 particles with a primary diameter of 50 nm (A50) were reported to induce interleukin (IL)‑1β production and secretion effectively in phorbol 12‑myristate 13‑acetate‑treated human monocytic leukemia THP‑1 cells (THP‑1 macrophages). We previously designed and synthesized dehydroxymethyl‑epoxyqinomicin (DHMEQ) as an inhibitor of NF‑κB. The present study investigated whether the NF‑κB inhibitor DHMEQ inhibits TiO2 nanoparticle‑induced IL‑1β production in THP‑1 macrophages, and determined the mechanism. As a result, DHMEQ inhibited A50‑induced IL‑1β secretion in ELISA assays at nontoxic concentrations. It decreased the expression of IL‑1β mRNA, which was dependent on NF‑κB. Although NLR family pyrin domain containing 3 (NLRP3)‑inflammasome‑caspase‑1 activation is required for the maturation of IL‑1β, and DHMEQ reduced the NLRP3 mRNA expression and caspase‑1 activity; a caspase‑1 inhibitor did not influence the A50‑induced IL‑1β production. Therefore, it is likely that inhibition of pro‑IL‑1β expression by DHMEQ may be sufficient to inhibit mature IL‑1β production. Thus, DHMEQ may be useful for the amelioration of inflammation in the trachea and lungs caused by inhalation of PM2.5.
doi10.3892/mmr.2018.9533
pmid30320338
issn17912997
date2018-12