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

Fukatsu,Hitomi; Koide,Naoki; Tada‑Oikawa,Saeko; Izuoka,Kiyora; Ikegami,Akihiko; Ichihara,Sahoko; Ukaji,Tamami; Morita,Naoko; Naiki,Yoshikazu; Komatsu,Takayuki; Umezawa,Kazuo

doi:10.3892/mmr.2018.9533

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

Authors:
- Hitomi Fukatsu
- Naoki Koide
- Saeko Tada‑Oikawa
- Kiyora Izuoka
- Akihiko Ikegami
- Sahoko Ichihara
- Tamami Ukaji
- Naoko Morita
- Yoshikazu Naiki
- Takayuki Komatsu
- Kazuo Umezawa
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Affiliations: Department of Molecular Target Medicine, Aichi Medical University, Nagakute, Aichi 480‑1195, Japan, Department of Microbiology and Immunology, Aichi Medical University, Nagakute, Aichi 480‑1195, Japan, School of Life Studies, Sugiyama Jogakuen University, Nagoya, Aichi 464‑8662, Japan, Graduate School of Regional Innovation Studies, Mie University, Tsu, Mie 514‑8507, Japan, Department of Environmental and Preventive Medicine, Jichi Medical University, Shimotsuke, Tochigi 329‑0498, Japan
Published online on: October 3, 2018 https://doi.org/10.3892/mmr.2018.9533
Pages: 5279-5285

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Abstract

PM2.5 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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