NFκB inhibitor DHMEQ inhibits titanium dioxide nanoparticleinduced interleukin1ß production: Inhibition of the PM2.5induced inflammation model.
Mol Med Rep
; 18(6): 5279-5285, 2018 Dec.
Article
em En
| MEDLINE
| ID: mdl-30320338
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 nanomicrosized 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, Anatasetype TiO2 particles with a primary diameter of 50 nm (A50) were reported to induce interleukin (IL)1ß production and secretion effectively in phorbol 12myristate 13acetatetreated human monocytic leukemia THP1 cells (THP1 macrophages). We previously designed and synthesized dehydroxymethylepoxyqinomicin (DHMEQ) as an inhibitor of NFκB. The present study investigated whether the NFκB inhibitor DHMEQ inhibits TiO2 nanoparticleinduced IL1ß production in THP1 macrophages, and determined the mechanism. As a result, DHMEQ inhibited A50induced IL1ß secretion in ELISA assays at nontoxic concentrations. It decreased the expression of IL1ß mRNA, which was dependent on NFκB. Although NLR family pyrin domain containing 3 (NLRP3)inflammasomecaspase1 activation is required for the maturation of IL1ß, and DHMEQ reduced the NLRP3 mRNA expression and caspase1 activity; a caspase1 inhibitor did not influence the A50induced IL1ß production. Therefore, it is likely that inhibition of proIL1ß expression by DHMEQ may be sufficient to inhibit mature IL1ß production. Thus, DHMEQ may be useful for the amelioration of inflammation in the trachea and lungs caused by inhalation of PM2.5.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Titânio
/
Benzamidas
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NF-kappa B
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Cicloexanonas
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Interleucina-1beta
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Nanopartículas
Tipo de estudo:
Etiology_studies
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Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article