2022 journal article

Synergistic induction of IL-6 production in human bronchial epithelial cells in vitro by nickel nanoparticles and lipopolysaccharide is mediated by eSTAT3 and C/EBP beta

TOXICOLOGY IN VITRO, 83.

By: D. You n, H. Lee n, A. Taylor-Just n & J. Bonner n

author keywords: Nanoparticles; Nickel; Lipopolysaccharide; Cytokines; Cell signaling; Epithelial cells
MeSH headings : Animals; CCAAT-Enhancer-Binding Protein-beta / metabolism; Cell Line; Epithelial Cells; Female; Humans; Interleukin-6 / genetics; Interleukin-6 / metabolism; Lipopolysaccharides / pharmacology; Male; Mice; Nanoparticles; Nickel; STAT3 Transcription Factor / metabolism
TL;DR: The data suggest that LPS and NiNPs induce IL-6 via STAT3 and C/EBPβ in BEAS-2B cells, and that these cells do not appear to be suitable for studying the effect of sex hormones. (via Semantic Scholar)
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Added: August 15, 2022

We previously reported that delivery of nickel nanoparticles (NiNPs) and bacterial lipopolysaccharide (LPS) into the lungs of mice synergistically increased IL-6 production and inflammation, and male mice were more susceptible than female mice. The primary goal of this study was to utilize an in vitro human lung epithelial cell model (BEAS-2B) to investigate the intracellular signaling mechanisms that mediate IL-6 production by LPS and NiNPs. We also investigated the effect of sex hormones on NiNP and LPS-induced IL-6 production in vitro. LPS and NiNPs synergistically induced IL-6 mRNA and protein in BEAS-2B cells. TPCA-1, a dual inhibitor of IKK-2 and STAT3, blocked the synergistic increase in IL-6 caused by LPS and NiNPs, abolished STAT3 activation, and reduced C/EBPβ. Conversely, SC144, an inhibitor of the gp130 component of the IL-6 receptor, enhanced IL-6 production induced by LPS and NiNPs. Treatment of BEAS-2B cells with sex hormones (17β-estradiol, progesterone, or testosterone) or the anti-oxidant NAC, had no effect on IL-6 induction by LPS and NiNPs. These data suggest that LPS and NiNPs induce IL-6 via STAT3 and C/EBPβ in BEAS-2B cells. While BEAS-2B cells are a suitable model to study mechanisms of IL-6 production, they do not appear to be suitable for studying the effect of sex hormones.