interleukin-8 and nickel-monoxide

Nickel oxide nanoparticles (NiONPs) toxicity has been evaluated in the human pulmonary epithelial cell lines: BEAS-2B and A549. The nanoparticles, used at the doses of 20, 40, 60, 80, 100 μg/ml, induced a significant reduction of cell viability and an increase of apoptotic and necrotic cells at 24h. A significant release of interleukin-6 and -8 was assessed after 24h of treatment, even intracellular ROS increased already at 45 min after exposure. The results obtained evidenced that the cytokines release was dependent on mitogen activated protein kinases (MAPK) cascade through the induction of NF-kB pathway. NiONPs induced cell cycle alteration in both the cell lines even in different phases and these modifications may be induced by the NPs genotoxic effect, suggested by the nuclear translocation of phospho-ATM and phospho-ATR. Our results confirm the cytotoxic and pro-inflammatory potential of NiONPs. Moreover their ability in inducing DNA damage responses has been demonstrated. Such effects were present in A549 cells which internalize the NPs and BEAS-2B cells in which endocytosis has not been observed.

Topics: Alveolar Epithelial Cells; Apoptosis; Ataxia Telangiectasia Mutated Proteins; Cell Cycle; Cell Line, Tumor; Cell Survival; DNA Damage; Dose-Response Relationship, Drug; Endocytosis; Humans; Inflammation Mediators; Interleukin-6; Interleukin-8; MAP Kinase Signaling System; Metal Nanoparticles; Mutagens; Necrosis; NF-kappa B; Nickel; Phosphorylation; Reactive Oxygen Species; Respiratory Mucosa; Time Factors

Abstract Nickel, zinc, and copper oxide nanoparticles (NiONP, ZnONP, and CuONP) and their aqueous extracts (AEs) were applied to A549 lung epithelial cells to determine the cytotoxicity, IL-8 production, and activation of transcription factors. Nanoparticles (NPs) and their AEs were also instilled into rat lungs to evaluate acute and chronic inflammatory effects. In vitro AEs had specific effects; for example NiOAE had no effect and ZnOAE affected all parameters measured. NPs themselves all had cytotoxic effects but only ZnONP and CuONP impacted pro-inflammatory endpoints. The inflammatory cells in the BAL were also different from AEs and NPs with ZnONP and CuONP recruiting eosinophils and neutrophils whilst ZnOAE and CuOAE elicited only mild neutrophilic inflammation that had resolved by four weeks. NiONP recruited neutrophils only whilst NiOAE did not cause any inflammation. Understanding differences in the toxic role of the ionic components of metal oxide NPs will contribute to full hazard identification and characterisation.

Topics: Alveolar Epithelial Cells; Animals; Bronchoalveolar Lavage Fluid; Cattle; Cell Line, Tumor; Cell Survival; Chemotaxis, Leukocyte; Copper; Eosinophils; Humans; Interleukin-8; Intubation, Intratracheal; Ions; Lung; Metal Nanoparticles; Neutrophils; Nickel; Oxides; Rats; Transcription Factor AP-1; Zinc Oxide