The roles of monocytic heat shock protein 60 and Toll-like receptors in the regional inflammation response to wear debris particles.
The biological response to orthopaedic wear debris is central to peri-prosthetic tissue inflammation and osteolysis, through mechanisms that include local inflammatory cytokine production. In particular, interleukin-1 beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha|) are generated in high quantities following monocyte accumulation in periprosthetic inflammatory tissue, and these cytokine combine with other inflammatory mediators to trigger osteolysis. Since the precise mechanisms involved in debris-associated inflammation remain unclear, it is important to understand how wear debris particles initially interact with inflammatory cells. We have previously demonstrated that the severity of the inflammation response is influenced by the size, shape, and quantity of particles accumulated in tissues. The current in vitro and in vivo results indicate that heat-shock protein (Hsp) expression is elevated when monocytes are exposed to wear debris particles. We have also addressed the mechanisms by which heat-shock protein 60 (Hsp60) positively modulates inflammatory cytokines via Toll-like receptor-4 (TLR4) signal transduction pathway on mononuclear cells. Furthermore, down-regulation of TLR4 expression using antisense oligonucleotides targeted to TLR4 mRNA suppressed cytokine production in both exogenous Hsp60 and particles stimulated cultures. Collectively, these data indicate that monocytic Hsp60 is an additional inducible immunoregulatory mediator in response to particle-induced cell stress.
Department of Orthopaedic Surgery, Wayne State University School of Medicine, Detroit, Michigan, USA. ab0770@wayne.edu
Hsiao-Nan
HN
Hao
Bingrong
B
Zheng
Sam
S
Nasser
Weiping
W
Ren
Michael
M
Latteier
Paul
P
Wooley
Lawrence
L
Morawa
D000328:Adult; D000818:Animals; D002478:Cells, Cultured; D018834:Chaperonin 60 / Q000235:genetics / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000139:chemically induced* / Q000276:immunology; D018836:Inflammation Mediators / Q000276:immunology; D053583:Interleukin-1beta / Q000276:immunology; D007595:Joint Prosthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D010316:Particle Size; D011095:Polyethylenes / Q000737:chemistry / Q000494:pharmacology*; D011475:Prosthesis Failure; D051193:Toll-Like Receptors / Q000235:genetics / Q000276:immunology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D018834:Chaperonin 60; D004268:DNA-Binding Proteins; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D016376:Oligonucleotides, Antisense; D011095:Polyethylenes; D051193:Toll-Like Receptors; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; C111601:ultra-high molecular weight polyethylene; C070389:HSF2 protein, human