title: Lipoteichoic acid modulates inflammatory response in macrophages after phagocytosis of titanium particles through Toll-like receptor 2 cascade and inflammasomes.
abstract: Toll-like receptor 2 (TLR2) and nucleotide-binding and oligomerization domain-like receptors with a pyrin domain 3 (NLRP3) inflammasomes have been presumed to participate in the pathogenesis of aseptic implant loosening. The aim of this study is to analyze the cellular localization of TLR2 and NLRP3 inflammasomes in the periprosthetic tissue from aseptically loose hip implants as well as the expression of these molecules in macrophages stimulated in vitro with titanium particles (Ti) coated with lipoteichoic acid (LTA). Using immunohistochemistry, immunoreactivity of TLR2 and NLRP3 inflammasomes was found in macrophages within the foreign body granulomatosis. Using RAW264.7 cells, stimulation with Ti increased the messenger RNA (mRNA) levels of TLR2 and TNF-α. Stimulation with LTA-coated Ti enhanced mRNA levels of NLRP3 and IL-1β, whereas reinforced secretion of IL-1β was not detected in spite of marked release of TNF-α. Finally, the same cells with silenced Irak2, an adaptor protein in the TLR2 cascade, suppressed this NLRP3 upregulation. This study suggests that TLR2 and NLRP3 inflammasomes are factors involved in cross-talk mediating the foreign body type response to wear particles. In addition, discrepant behavior in the release between TNF-α and IL-1β release may explain the variable pathomechanisms of aseptic implant loosening without acute inflammatory reactions.
authors.affiliation: Department of Orthopaedic Surgery, Yamagata University Faculty of Medicine, Yamagata, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Naganuma
authors.affiliation: Department of Orthopaedic Surgery, Yamagata University Faculty of Medicine, Yamagata, Japan.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Takakubo
authors.affiliation: Department of Orthopaedic Surgery, Yamagata University Faculty of Medicine, Yamagata, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Hirayama
authors.affiliation: Department of Clinical Medicine, Yamagata Saisei Hospital, Yamagata, Japan.
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Tamaki
authors.affiliation: Department of Orthopaedic Surgery, Stanford University School of Medicine, California, 94063.|Department of Medicine, Biomedicum Helsinki, University of Helsinki, Helsinki, FIN-00014 HY, Finland.
authors.forename: Jukka
authors.initials: J
authors.lastname: Pajarinen
authors.affiliation: Department of Orthopaedic Surgery, Yamagata University Faculty of Medicine, Yamagata, Japan.
authors.forename: Kan
authors.initials: K
authors.lastname: Sasaki
authors.affiliation: Department of Orthopaedic Surgery, Stanford University School of Medicine, California, 94063.
authors.forename: Stuart B
authors.initials: SB
authors.lastname: Goodman
authors.affiliation: Department of Orthopaedic Surgery, Yamagata University Faculty of Medicine, Yamagata, Japan.
authors.forename: Michiaki
authors.initials: M
authors.lastname: Takagi
mesh_terms: D000368:Aged; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D005260:Female; D005549:Foreign-Body Reaction / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008875:Middle Aged; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D010587:Phagocytosis; D013682:Teichoic Acids / Q000494:pharmacology*; D014025:Titanium / Q000009:adverse effects*; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; C508585:IL1B protein, human; C587672:IL1B protein, mouse; D058847:Inflammasomes; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; C492716:Nlrp3 protein, mouse; C495342:TLR2 protein, human; D013682:Teichoic Acids; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha; C009900:lipoteichoic acid; D014025:Titanium
keywords: NLRP3 inflammasomes; Toll-like receptors; cellular innate immune response; osteolysis; total hip arthroplasty