Involvement of L‐type Ca²⁺ channel and toll‐like receptor‐4 in nickel‐induced interleukin‐8 gene expression

Abstract

The metal nickel (Ni(2+)) is found everywhere in our daily lives, including coins, costume jewelry, and even nuts and chocolates. Nickel poisoning can cause inflammatory reactions, respiratory diseases, and allergic contact dermatitis. To clarify the mechanism by which nickel induces mediators of inflammation, we used the human acute monocytic leukemia THP-1 cell line as a model. Interleukin (IL)-8 promoter activity as well as gene expression were tested by luciferase assay and real-time polymerase chain reaction. The underlying mechanisms of nickel-induced IL-8 were investigated. We found that nickel induced IL-8 gene expression via the L-type Ca(2+) channel, Toll-like receptor-4 (TRL-4) and nuclear factor NF-κB signal transduction pathways. Nickel activated NF-κB expression through extracellular signal-regulated kinase 1/2 phosphorylation and then increased IL-8 expression. Thus, the L-type Ca(2+) channel and TRL-4 play important roles in nickel-induced inflammatory gene expressions.

Cytokine patterns in vitro, in particular IL‐5/IL‐8 ratio, to detect patients with nickel contact allergy

“…The potential underlying mechanism of such nickel‐induced IL‐8 production could be that described by Lin and coworkers in 2016. They postulated an ‘IL‐8 gene expression via the L‐type Ca(2+) channel, Toll‐like receptor‐4 (TRL‐4) and nuclear factor NF‐κB signal transduction pathways’ . This would be in accordance with results published by Tsou et al .…”

Update of the risk assessment of nickel in food and drinking water

“…These results indicate that nickel-induced Th17 cell development is dependent on the production of IL-23 by human monocyte-derived dendritic cells via toll-like receptor 4 (TLR4), p38 MAPK, NF-jB and Jak-signal transducer and activator of transcription pathways. Similar observations on TLR4 and NF-jB involvement were made by Zoroddu et al (2014), Lin et al (2016), Oblak et al (2015) and Peana et al (2017). Almogren et al (2013) observed a predominance of a Th1 phenotype, based on cytokine expression including IL-4 and IL-10, of lymphocytes collected from patients suffering from nickel allergy, in line with commonly accepted mechanisms of contact sensitivity.…”

Transcriptome Profiling and Toxicity Following Long-Term, Low Dose Exposure of Human Lung Cells to Ni and NiO Nanoparticles—Comparison with NiCl2

“…The role of extracellular-and calcium-dependent mechanisms has also been proposed in other reports on toxicity of Ni. For example, a study using THP-1 cells to investigate mechanisms for Ni-induced changes on IL-8 gene expression demonstrated the role of an extracellular mechanism via TLR-4 and the L-type Ca 2+ channel, followed by the downstream extracellular signal-regulated kinases (ERKs) and NF-κB signaling pathways [27]. Indeed, ERK/MAPK signaling was predicted in the IPA analysis for Ni NPs and NiCl 2 in our study ( Figure 5).…”