RRC ID 56146
Author Fukatsu H, Koide N, Tada-Oikawa S, Izuoka K, Ikegami A, Ichihara S, Ukaji T, Morita N, Naiki Y, Komatsu T, Umezawa K.
Title NF‑κB inhibitor DHMEQ inhibits titanium dioxide nanoparticle‑induced interleukin‑1β production: Inhibition of the PM2.5‑induced inflammation model.
Journal Mol Med Rep
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.
Volume 18(6)
Pages 5279-5285
Published 2018-12-1
DOI 10.3892/mmr.2018.9533
PMID 30320338
MeSH Animals Benzamides / pharmacology* Biomarkers Caspase 1 / metabolism Caspase Inhibitors / pharmacology Cell Line Cyclohexanones / pharmacology* Disease Models, Animal Humans Inflammation / etiology Inflammation / metabolism Inflammation / pathology Interleukin-1beta / biosynthesis* Macrophages / metabolism Models, Molecular NF-kappa B / antagonists & inhibitors* Nanoparticles* / chemistry Particulate Matter Potassium / metabolism Titanium* / chemistry
IF 1.851
Times Cited 4
Human and Animal Cells THP-1(RCB1189)