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Concentration‐dependent cytokine responses of silica nanoparticles and role of ROS in human lung epithelial cells
Author(s) -
Refsnes Magne,
Skuland Tonje,
Lilleaas Edel,
Øvrevik Johan,
Låg Marit
Publication year - 2019
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.13221
Subject(s) - reactive oxygen species , interleukin 8 , nadph oxidase , p38 mitogen activated protein kinases , chemistry , signal transduction , phosphorylation , microbiology and biotechnology , cytokine , oxidative stress , inflammation , biochemistry , mapk/erk pathway , biology , immunology
Reactive oxygen species (ROS) is regarded as a critical denominator in nanoparticle toxicology and inflammation. Previously, we have shown that silica nanoparticles sized 50 nm (Si50) induce release of CXCL8 and IL‐6 from BEAS‐2B cells, via mechanisms involving NFκB, p38 MAP kinase and TGF‐α‐activated EGF receptor. In the present study, the role of ROS‐mediated mechanisms in the concentration‐dependent Si50 induction of CXCL8 and IL‐6 responses was examined. Si50 (200 µg/mL) induced a time‐dependent ROS formation and a postponed increase in expression of haem oxygenase (HO‐1) mRNA and protein. Pre‐treatment with the ROS inhibitors N‐acetyl cysteine (NAC) and diphenyleneiodonium (DPI) partially attenuated CXCL8 and IL‐6 responses to 200 µg/mL, but not to 100 µg/mL Si50. The release of TGF‐α induced by Si50 (200 µg/mL) was significantly reduced by NAC, but not by DPI nor siRNA against NADPH oxidase DUOX‐1 (siDUOX‐1). Furthermore, siDUOX‐1 reduced Si50‐induced CXCL8, but not IL‐6. Both p38 and p65 phosphorylations were inhibited by siDUOX‐1, but for NAC only p65 phosphorylation reached a significant reduction. Neither NAC nor DPI reduced Si50‐induced CXCL8 and IL‐6 gene expressions. In conclusion, Si50‐induced CXCL8 and IL‐6 involved both ROS‐dependent and ROS‐independent mechanisms. Notably, the role of ROS seemed restricted to effects of higher concentrations of Si50 and not mediated via the gene expression.