Role of scavenger receptors in silica nanoparticle-induced cytokine responses in bronchial epithelial cells

A major challenge in nanoparticle (NP) research is to elucidate how NPs activate initial targets in cells, leading to cytotoxicity and inflammation. We have previously shown that silica (Si)NPs induce pro inflammatory responses in bronchial epithelial cells (BEAS-2B) via mechanisms involving transforming growth factor (TGF)-alpha release, and activation of MAP-kinase p38 and JNK besides NF-KB (p65). In the present study, the roles of scavenger receptors (SRs) in SiNP-induced cytokine responses in BEAS-2B cells were examined by siRNA silencing. Cells exposed to Si10 and Si50 (nominal sizes 10 and 50 nm) showed marked interleukin (IL)-6, CXCL8, IL-1 alpha, IL-1 beta responses. Transient knockdown of SR-B1, LOX-1 and CXCL16 reduced the Si10-and Si50-induced cytokine responses, to a different magnitude dependent on the particle size, SR and cytokine. Si10-induced TGF-alpha responses were also markedly reduced by knockdown of SR-B1 and CXCL16. Furthermore, the role of SR-B1 in Si10-induced phosphorylations of p65 and MAP-kinases p38 and JNK were examined, and no significant reductions were observed upon knockdown of SR-B1. In conclusion, LOX-1 and CXCL16 and especially SR-B1 seem to have important roles in mediating cytokine responses and TGF-alpha release due to SiNP exposure in BEAS-2B cells, without a down-stream role of MAP-kinase and NF-KB. (C) 2021 The Authors. Published by Elsevier B.V.

Automated summary

The study found that silica nanoparticles can induce inflammatory responses in bronchial epithelial cells through different mechanisms, with scavenger receptors (SRs) playing important roles in mediating cytokine responses and TGF-α release. Specifically, SR-B1 seems to be crucial in mediating these responses, while MAP-kinases and NF-KB do not appear to have downstream effects in this process.