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

Magne Refsnes,Tonje Skuland,Johan Øvrevik,Marit Låg

doi:10.1016/j.toxlet.2021.10.004

Magne Refsnes, Tonje Skuland + Show 2 more

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https://doi.org/10.1016/j.toxlet.2021.10.004

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Journal: Toxicology Letters	Publication Date: Oct 12, 2021
Citations: 2	License type: cc-by

Affiliation: Norwegian Institute of Public Health

Abstract

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)-α release, and activation of MAP-kinase p38 and JNK besides NF-κB (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-1α, IL-1β 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-α 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-α release due to SiNP exposure in BEAS-2B cells, without a down-stream role of MAP-kinase and NF-κB.

Highlights

The use of engineered nanoparticles (NPs) in the development of new materials, giving advantageous properties for consumer products and therapeutics, is rapidly increasing word-wide
It is of uttermost importance to avoid that these new NP/nanomaterials (NM) possess properties that induce adverse acute or chronic health effects in humans or affect the Abbreviations: NPs, Nanoparticles; SiNPs, Silica nanoparticles; size of 10 nm (Si10), SiNPs with nominal size 10 nm; BEAS-2B, bronchial epithelial cells 2B; scavenger receptors (SRs)-B1, scavenger receptor B1; LOX-1, lectin-like oxidized LDL receptor-1; CXCL16, C-X-C motif chemokine ligand 16; IL, interleukin; TGF-α, transforming growth factor-α; TACE, tumour necrosis factor-α converting enzyme
We have previously shown that the SiNP-induced IL-6 and CXCL8 responses in BEAS-2B cells involve p38 mitogen-activated protein kinase (MAP-kinase) and c-Jun N-terminal kinases (JNK), and nuclear factor-kB (NF-kB) signalling, as well as cleavage and release of membrane-bound transforming growth factor-α (TGF-α) through tumour necrosis factor-α converting enzyme (TACE) (Låg et al, 2018; Skuland et al, 2014b)

Summary

Introduction

The use of engineered nanoparticles (NPs) in the development of new materials, giving advantageous properties for consumer products and therapeutics, is rapidly increasing word-wide. It is of uttermost importance to avoid that these new NP/nanomaterials (NM) possess properties that induce adverse acute or chronic health effects in humans or affect the Abbreviations: NPs, Nanoparticles; SiNPs, Silica nanoparticles; Si10, SiNPs with nominal size 10 nm; BEAS-2B, bronchial epithelial cells 2B; SR-B1, scavenger receptor B1; LOX-1, lectin-like oxidized LDL receptor-1; CXCL16, C-X-C motif chemokine ligand 16; IL, interleukin; TGF-α, transforming growth factor-α; TACE, tumour necrosis factor-α converting enzyme. We have previously shown that the SiNP-induced IL-6 and CXCL8 responses in BEAS-2B cells involve p38 mitogen-activated protein kinase (MAP-kinase) and c-Jun N-terminal kinases (JNK), and nuclear factor-kB (NF-kB) signalling, as well as cleavage and release of membrane-bound transforming growth factor-α (TGF-α) through tumour necrosis factor-α converting enzyme (TACE) (Låg et al, 2018; Skuland et al, 2014b). SiNP -induced cytokine responses partially seem to involve reactive oxygen species (ROS)-dependent mechanisms in the BEAS-2B cells, at high, but not low concentrations of SiNPs with nominal size of 50 nm (Si50) (Refsnes et al, 2019)

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