title: Involvement of toll-like receptor 4 in the inflammatory reaction induced by hydroxyapatite particles.
abstract: Hydroxyapatite (HA) is widely used to coat metal parts in order to improve their biocompatibility. Analysis of retrieved tissues associated with failed implants, suggest that phagocytosis of HA wear debris by monocytes/macrophages might provide a potent stimulus for the release of a variety of cytokines. Phagocytosis involved a large variety of cellular receptors like toll-like receptors that results in activation of the transcriptional nuclear factor-kappaB (NF-kappaB) via a cell-signalling pathway. In the present paper, we aimed to evaluate the role of the toll-like receptor 4 (TLR4) in the production of inflammatory cytokines induced by HA particles using TLR4(+) and TLR4(-) peritoneal macrophages. We investigated the production of TNF-alpha and the activation of the nuclear transcription factor NF-kappaB. Our data clearly show for the first time that the production of TNF-alpha by macrophages exposed to HA particles was TLR4 dependent but not the activation of NF-kappaB. All these results open future therapies to reduce the inflammatory response induced by HA biomaterials.
authors.affiliation: INSERM, ERM 0203, IFR 53, 1 rue du Maréchal Juin, BP 138, 51095 Reims, Cedex, France. alexia.laquerriere@univ-reims.fr
authors.forename: Alexia
authors.initials: A
authors.lastname: Grandjean-Laquerriere
authors.forename: Olivier
authors.initials: O
authors.lastname: Tabary
authors.forename: Jacky
authors.initials: J
authors.lastname: Jacquot
authors.forename: Doriane
authors.initials: D
authors.lastname: Richard
authors.forename: Patrick
authors.initials: P
authors.lastname: Frayssinet
authors.forename: Moncef
authors.initials: M
authors.lastname: Guenounou
authors.forename: Dominique
authors.initials: D
authors.lastname: Laurent-Maquin
authors.forename: Patrice
authors.initials: P
authors.lastname: Laquerriere
authors.forename: Sophie
authors.initials: S
authors.lastname: Gangloff
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D017886:Durapatite / Q000737:chemistry*; D007249:Inflammation; D008070:Lipopolysaccharides / Q000737:chemistry; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D009000:Monocytes / Q000166:cytology*; D016328:NF-kappa B / Q000378:metabolism; D010587:Phagocytosis; D011208:Powders; D013499:Surface Properties; D051197:Toll-Like Receptor 4 / Q000378:metabolism / Q000502:physiology*
chemical_list: D001672:Biocompatible Materials; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011208:Powders; D051197:Toll-Like Receptor 4; D017886:Durapatite