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 mRNA levels of TLR2 and TNF-a. Stimulation with LTA-coated Ti enhanced mRNA levels of NLRP3 and IL-1ß, whereas, reinforced secretion of IL-1ß was not detected in spite of marked release of TNF-a. 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-a and IL-1ß release may explain the variable pathomechanisms of aseptic implant loosening without acute inflammatory reactions. This article is protected by copyright. All rights reserved.

View details for DOI 10.1002/jbm.a.35581

View details for Web of Science ID 000368271600011