title: The role of oxidative stress in pro-inflammatory activation of human endothelial cells on Ti6Al4V alloy.
abstract: Inflammation is an important step in the early phase of tissue regeneration around an implanted metallic orthopaedic device. However, prolonged inflammation, which can be induced by metallic corrosion products, can lead to aseptic loosening and implant failure. Cells in peri-implant tissue as well as metal corrosion can induce reactive oxygen species (ROS) formation, thus contributing to an oxidative microenvironment around an implant. Understanding cellular reactions to implant-induced oxidative stress and inflammatory activation is important to help prevent an adverse response to metallic materials. In an earlier study we have shown that endothelial cells grown on Ti6Al4V alloy are subjected to oxidative stress. Since endothelial cells play a critical role in inflammation, in this study we examined the role of oxidative stress in their response to pro-inflammatory activation. Therefore, we stimulated endothelial cells in contact with Ti6Al4V with tumour necrosis factor-α (TNF-α) and monitored the expression of inflammation-associated molecules, such as E-selectin, intercellular adhesion molecule-1 (ICAM-1) and interleukin-8 (IL-8). The induction of these proteins was lower in endothelial cells on Ti6Al4V compared to control tissue culture conditions. There was, however, a discrepancy in pro-inflammatory activation at protein compared to mRNA level in the cells on Ti6Al4V. To examine the role of oxidative stress in this response we utilized different ROS scavengers and showed that ROS depletion improved cellular response to TNF-α on Ti6Al4V. These results could contribute to developing strategies to improve tissue response to metal implants.
authors.affiliation: Institute of Pathology, University Medical Center, Johannes Gutenberg University of Mainz, Langenbeckstr. 1, Mainz 55131, Germany. tsaryk@uni-mainz.de
authors.forename: Roman
authors.initials: R
authors.lastname: Tsaryk
authors.forename: Kirsten
authors.initials: K
authors.lastname: Peters
authors.forename: Susanne
authors.initials: S
authors.lastname: Barth
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Unger
authors.forename: Dieter
authors.initials: D
authors.lastname: Scharnweber
authors.forename: C James
authors.initials: CJ
authors.lastname: Kirkpatrick
mesh_terms: D000497:Alloys; D000975:Antioxidants / Q000378:metabolism; D002460:Cell Line; D042783:Endothelial Cells / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014025:Titanium / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000497:Alloys; D000975:Antioxidants; D016209:Interleukin-8; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; C031462:titanium alloy (TiAl6V4); D014025:Titanium
keywords: Antioxidant; Endothelial cell; Inflammation; Titanium alloy