interleukin-8 and nickel-chloride

The spontaneous IL-8 secretion observed in OSCC is partially dependent on the disregulated activity of transcription factor NF-κB. Nickel compounds are well established human carcinogens, however, little is known about the influence of nickel on the spontaneous secretion of IL-8 in oral squamous cell carcinoma (OSCC) cells. The aim of the present study was to investigate whether Ni(2+) ions can influence on IL-8 secretion by OSCC.. The IL-8 secretion was measured by ELISA. The expression of IL-8 mRNA was examined by real-time PCR. The NF-κB activity was measured by luciferase assay. The phosphorylation status and nuclear localization of NF-κB subunits were examined by Western blotting or Transfactor kit and immunofluorescence staining, respectively. The interaction of NF-κB p50 subunit and Ni(2+) ions was examined by Ni(2+)-column pull down assay. The site-directed mutagenesis was used to generate a series of p50 mutants. Scratch motility assay was used to monitor the cell mobility. Our results demonstrated that, on the contrary to our expectations, Ni(2+) ions inhibited the spontaneous secretion of IL-8. As IL-8 reduction was observed in a transcriptional level, we performed the luciferase assay and the data indicated that Ni(2+) ions reduced the NF-κB activity. Measurement of p50 subunit in the nucleus and the immunofluorescence staining revealed that the inhibitory effect of Ni(2+) ions was attributed to the prevention of p50 subunit accumulation to the nucleus. By Ni(2+)-column pull down assay, Ni(2+) ions were shown to interact directly with His cluster in the N-terminus of p50 subunit. The inhibitory effect of Ni(2+) ions was reverted in the transfectant expressing the His cluster-deleted p50 mutant. Moreover, Ni(2+) ions inhibited the OSCC mobility in a dose dependent fashion.. Taken together, inhibition of NF-κB activity by Ni(2+) ion might be a novel therapeutic strategy for the treatment of oral cancer.

Topics: Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Movement; Enzyme Activation; Gene Expression; Heavy Ions; Humans; Interleukin-8; Mouth Neoplasms; NF-kappa B; NF-kappa B p50 Subunit; Nickel; Protein Binding; Protein Transport; Toll-Like Receptor 4

Epidemiological studies have demonstrated a close correlation between nickel exposure and the incidence of lung cancer. Several studies have suggested that nickel contributes to tumor progression of human lung cancer. In this in vitro study, we found that nickel, as nickel chloride, could significantly enhance the invasive potential of human lung cancer cells, accompanied by elevated expression of IL-8, TGF-β, MMP2 and MMP9 in human lung cancer cells. Importantly, we demonstrated that nickel could activate TLR4 signaling in human lung cancer cells. Further studies showed that the TLR4/MyD88 signaling conferred the enhanced invasive potential of human lung cancer cells induced by nickel. Finally, we revealed that the p38MAPK pathway and NF-kB pathway were necessary for the enhanced invasive potential of human lung cancer cells induced by nickel. Our data provide a mechanistic explanation for nickel induced invasion of human lung cancer, and they suggest new strategies for nickel-related lung cancer clinical biotherapies.

Topics: Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Humans; Interleukin-8; Lung Neoplasms; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Myeloid Differentiation Factor 88; Neoplasm Invasiveness; NF-kappa B; Nickel; p38 Mitogen-Activated Protein Kinases; Signal Transduction; Toll-Like Receptor 4; Transforming Growth Factor beta

A three-dimensional human tissue model based on TR146 cells isolated from a squamous cell carcinoma of the buccal mucosa was used to test for the release of the proinflammatory molecules prostaglandin E2 (PGE2), interleukin 6 (IL-6), and interleukin 8 (IL-8) after exposure to nickel chloride (NiCl2), cobalt chloride (COCl2), palladium chloride (PdCl2), and triethylene glycol dimethacrylate (TEGDMA). These compounds have documented adverse biological effects in vitro. The release of PGE2 from the tissue culture models was inversely correlated with cell viability (MTT assay). Toxic concentrations of NiCl2 and CoCl2 induced the release of PGE2 by factors of about 200-300 compared to controls, but PdCl2 which was nontoxic enhanced PGE2 levels about 10-fold. TEGDMA, however, did not stimulate PGE2 release. None or weakly toxic concentrations of Ni and Co chloride induced IL-6 and IL-8 release by a factor of 5-10 compared to controls. The amounts of IL-6 were induced 25- to 30-fold by PdCl2 under physiological conditions, and IL-8 levels were also slightly enhanced. Nontoxic TEGDMA concentrations induced IL-6 levels 5-fold, but IL-8 amounts increased only slightly. We conclude that a steep rise of PGE2 is closely associated with cytotoxicity. On the other hand, the specific induction of IL-6 occurs at much lower concentrations. Therefore, the measurement of this cytokine may be included as another parameter in evaluating the biological activity of dental materials under nontoxic experimental conditions in vitro.

Topics: Biocompatible Materials; Carcinoma, Squamous Cell; Cell Survival; Cobalt; Culture Techniques; Dental Materials; Dinoprostone; Epithelial Cells; Humans; Interleukin-6; Interleukin-8; Interleukins; Materials Testing; Mitochondria; Models, Biological; Mouth Mucosa; Nickel; Palladium; Polyethylene Glycols; Polymethacrylic Acids; Statistics, Nonparametric; Tumor Cells, Cultured