Regulation of TLR4 in silica-induced inflammation: An underlying mechanism of silicosis

International Journal of Medical Sciences
Judy Y W ChanCarmen Wing Han Chan

Abstract

Silicosis is an incurable lung disease affecting millions of workers in hazardous occupations. It is caused by chronic exposure to the dust that contains free crystalline silica. Silica-induced lung damage occurs by several main mechanisms including cell death by apoptosis, fibrosis and production of cytokines. However, the signal pathways involved in these mechanisms are not fully characterized. In this study, the toll-like receptor 4 (TLR4)-related signal pathway was examined in silica-treated U937-differentiated macrophages. The expression level of TLR4 was measured by both quantitative PCR and Western blot. Confirmation of the involvement of MyD88/TIRAP and NFκB p65 cascade was performed by Western blot. The secretion of cytokines IL-1β, IL-6, IL-10 and TNFα was measured by enzyme-linked immunosorbent assay. Our results showed that TLR4 and related MyD88/TIRAP pathway was associated with silica-exposure in U937-differentiated macrophages. Protein expression of TLR4, MyD88 and TIRAP was upregulated when the U937-differentiated macrophages were exposed to silica. However, the upregulation was attenuated when TLR4 inhibitor, TAK-242 was present. At different incubation times of silica exposure, it was found that NFκB p65 casca...Continue Reading

Citations

Oct 3, 2020·International Journal of Molecular Sciences·Richard MussonJolanta Jura
Apr 5, 2020·Environmental Science and Pollution Research International·Grethel León-MejíaJoão Antônio Pêgas Henriques
Jan 21, 2021·International Journal of Molecular Sciences·Shiyi Tan, Shi Chen
Jun 16, 2021·Journal of Applied Toxicology : JAT·Caroline Portela PeruzziSolange Cristina Garcia
Jun 18, 2021·Journal of Inflammation Research·Rahnuma AhmadMainul Haque
Dec 11, 2021·Journal of Cellular and Molecular Medicine·RongLing HeJie Meng

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Methods Mentioned

BETA
X-ray
enzyme-linked immunosorbent assay
ELISA
PCR

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis