Int J Med Sci 2018; 15(10):986-991. doi:10.7150/ijms.24715 This issue Cite

Short Research Communication

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

Judy Yuet Wa Chan1,✉, Joseph Chi Ching Tsui2, Patrick Tik Wan Law3, Winnie Kwok Wei So1, Doris Yin Ping Leung1, Michael Mau Kwong Sham4, Stephen Kwok Wing Tsui5, Carmen Wing Han Chan1,✉

1. Nethersole School of Nursing, The Chinese University of Hong Kong, Shatin, Hong Kong
2. Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Shatin, Hong Kong
3. School of Life Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong
4. Grantham Hospital, Aberdeen, Hong Kong
5. School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong

Citation:
Chan JYW, Tsui JCC, Law PTW, So WKW, Leung DYP, Sham MMK, Tsui SKW, Chan CWH. Regulation of TLR4 in silica-induced inflammation: An underlying mechanism of silicosis. Int J Med Sci 2018; 15(10):986-991. doi:10.7150/ijms.24715. https://www.medsci.org/v15p0986.htm
Other styles

File import instruction

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 cascade was activated at 10-60 minutes. Release of cytokines IL-1β, IL-6, IL-10 and TNFα was induced by silica exposure and the induction of IL-1β, IL-6 and TNFα 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 NFκB 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.

Keywords: Silica, Macrophage, Toll-like receptor, Inflammation


Citation styles

APA
Chan, J.Y.W., Tsui, J.C.C., Law, P.T.W., So, W.K.W., Leung, D.Y.P., Sham, M.M.K., Tsui, S.K.W., Chan, C.W.H. (2018). Regulation of TLR4 in silica-induced inflammation: An underlying mechanism of silicosis. International Journal of Medical Sciences, 15(10), 986-991. https://doi.org/10.7150/ijms.24715.

ACS
Chan, J.Y.W.; Tsui, J.C.C.; Law, P.T.W.; So, W.K.W.; Leung, D.Y.P.; Sham, M.M.K.; Tsui, S.K.W.; Chan, C.W.H. Regulation of TLR4 in silica-induced inflammation: An underlying mechanism of silicosis. Int. J. Med. Sci. 2018, 15 (10), 986-991. DOI: 10.7150/ijms.24715.

NLM
Chan JYW, Tsui JCC, Law PTW, So WKW, Leung DYP, Sham MMK, Tsui SKW, Chan CWH. Regulation of TLR4 in silica-induced inflammation: An underlying mechanism of silicosis. Int J Med Sci 2018; 15(10):986-991. doi:10.7150/ijms.24715. https://www.medsci.org/v15p0986.htm

CSE
Chan JYW, Tsui JCC, Law PTW, So WKW, Leung DYP, Sham MMK, Tsui SKW, Chan CWH. 2018. Regulation of TLR4 in silica-induced inflammation: An underlying mechanism of silicosis. Int J Med Sci. 15(10):986-991.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Popup Image