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

J.Y.W. Chan, J.C.C. Tsui, P.T.W. Law, W.K.W. So, Yin Ping Leung, M.M.K. Sham, S.K.W. Tsui, C.W.H. Chan

Research output: Journal article publicationJournal articleAcademic researchpeer-review

12 Citations (Scopus)

Abstract

© Ivyspring International Publisher.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 NF?B p65 cascade was performed by Western blot. The secretion of cytokines IL-1?, IL-6, IL-10 and TNF? 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 NF?B p65 cascade was activated at 10-60 minutes. Release of cytokines IL-1?, IL-6, IL-10 and TNF? was induced by silica exposure and the induction of IL-1?, IL-6 and TNF? was suppressed by the addition of TAK-242. In conclusion, our study demonstrated that TLR4 and related MyD88/TIRAP pathway was involved in silica-induced inflammation in U937-differentiated macrophages. Downstream NF?B p65 cascade was activated within 1 hour when the U937-differentiated macrophages were exposed to silica. The better understanding of early stage of silica-induced inflammatory process may help to develop earlier diagnosis of silicosis.
Original languageEnglish
Pages (from-to)986-991
Number of pages6
JournalInternational Journal of Medical Sciences
Volume15
Issue number10
DOIs
Publication statusPublished - 14 Jun 2018
Externally publishedYes

Keywords

  • Inflammation
  • Macrophage
  • Silica
  • Toll-like receptor

ASJC Scopus subject areas

  • Medicine(all)

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