Exogenous Clara cell protein 16 attenuates silica particles-induced inflammation in THP-1 macrophages by down-regulating NF-κB and caspase-1 activation.
J Toxicol Sci
; 45(10): 651-660, 2020.
Article
em En
| MEDLINE
| ID: mdl-33012733
ABSTRACT
Inhalation of silica particles leads to pulmonary inflammatory responses. Clara cell protein 16 (CC16) has been reported to played a protective role in inflammatory lung diseases. However, its role on silica particles-induced inflammation has not been fully clarified. In this study, THP-1 macrophages were exposed to 75 µg/cm2 silica particles with or without 2 µg/mL exogenous CC16 (recombinant CC16, rCC16) for 24 hr. The production of inflammatory cytokines, including interleukin (IL)-1ß, tumor necrosis factor (TNF)-α and IL-6, in the cell supernatants of different groups was detected through ELISA kits and real-time RT-PCR, respectively. The nuclear translocation of nuclear factor (NF)-κB, protein levels of pro-IL-1ß, the nucleotide-binding domain-like receptor protein 3 (NLRP3) and caspase-1 were evaluated via immunofluorescence or western blot. Results showed that, at 75 µg/cm2 silica particle concentration, the treatment of rCC16 significantly decreased IL-1ß, TNF-α and IL-6 protein release and mRNA levels in THP-1 macrophages. Compared to those only exposed to silica particles, THP-1 macrophages exposed to both silica particles and rCC16 showed significantly lower nuclear levels and higher cytosol levels of NF-κB p65, as well as lower co-localization coefficients through immunofluorescence. Additionally, the administration of rCC16 significantly attenuated the increase of pro-IL-1ß, NLRP3 and caspase-1 levels induced by silica particle exposure. Our results suggested that exogenous CC16 could inhibit silica particles-induced inflammation in THP-1 macrophages, mainly through suppressing NF-κB pathway and caspase-1 activation.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Expressão Gênica
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NF-kappa B
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Macrófagos Alveolares
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Dióxido de Silício
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Caspase 1
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Inflamação
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Macrófagos
Limite:
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article