Toll‐like receptors and their adaptors are regulated in macrophages after phagocytosis of lipopolysaccharide‐coated titanium particles

Hirayama, Tomoyuki; Tamaki, Yasuhiro; Takakubo, Yuya; Iwazaki, Kiyoshi; Sasaki, Kan; Ogino, Toshihiko; Goodman, Stuart B.; Konttinen, Yrjö T.; Takagi, Michiaki

doi:10.1002/jor.21369

Cited by 62 publications

(69 citation statements)

References 45 publications

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“…The mRNA expression levels were calculated to cells stimulated with Ti 1 LTA and Ti, compared to unstimulated control cells, respectively. 13 PCR specificities of all examined PRRs, PRRs-associated molecules, and GAPDH were confirmed by melting curve analysis.…”

Section: 29mentioning

confidence: 79%

“…24,25 This suggests that assembly and activation of NLRP3 by wear particles could enhance periprosthetic osteolysis. 13 It has been also reported that the activated TLR2 cascade can potentiate joint inflammation via the NLRP3 cascade in crystal-induced arthritis. 26,27 This synergistic effect between TLR2 and NLRP3 may also enhance chronic inflammation around aseptically loose THA implants.…”

Section: Introductionmentioning

confidence: 98%

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Lipoteichoic acid modulates inflammatory response in macrophages after phagocytosis of titanium particles through Toll‐like receptor 2 cascade and inflammasomes

Naganuma

Takakubo

Hirayama

et al. 2015

J Biomedical Materials Res

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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.

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Section: 29mentioning

confidence: 79%

Section: Introductionmentioning

confidence: 98%

Lipoteichoic acid modulates inflammatory response in macrophages after phagocytosis of titanium particles through Toll‐like receptor 2 cascade and inflammasomes

Naganuma

Takakubo

Hirayama

et al. 2015

J Biomedical Materials Res

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“…However, the resultant osteolysis induced by particle exposure was only partially reduced, suggesting that titanium particles may also induce osteolysis in a TLR2 and TLR4 independent pathway. In vitro stimulation of rat bone marrow derived macrophages by titanium particles coated with LPS increased TLR2 expression but decreased TLR4, 5, and 9, suggesting a self-protective regulation may exist to restrict an excessive response 39 .…”

Section: Challengesmentioning

confidence: 96%

Interaction of materials and biology in total joint replacement – successes, challenges and future directions

et al. 2014

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Total joint replacement (TJR) has revolutionized the treatment of end-stage arthritic disorders. This success is due, in large part, to a clear understanding of the important interaction between the artificial implant and the biology of the host. All surgical procedures in which implants are placed in the body evoke an initial inflammatory reaction, which generally subsides over several weeks. Thereafter, a series of homeostatic events occur leading to progressive integration of the implant within bone and the surrounding musculoskeletal tissues. The eventual outcome of the operation is dependent on the characteristics of the implant, the precision of the surgical technique and operative environment, and the biological milieu of the host. If these factors and events are not optimal, adverse events can occur such as the development of chronic inflammation, progressive bone loss due to increased production of degradation products from the implant (periprosthetic osteolysis), implant loosening or infection. These complications can lead to chronic pain and poor function of the joint reconstruction, and may necessitate revision surgery or removal of the prosthesis entirely. Recent advances in engineering, materials science, and the immunological aspects associated with orthopaedic implants have fostered intense research with the hope that joint replacements will last a lifetime, and facilitate pain-free, normal function.

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“…TLR/PAMP interactions induce several immune cell functions, ranging from phagocytosis,11 migration,12 nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation13 to inflammatory cytokine expression 14. Accordingly, TLR9 activation leads to the expression of inflammatory cytokines, major histocompatibility complexes and homing molecules, via the detection of intracellular viral dsDNA in a MYD88-dependent manner 15.…”

Section: Introductionmentioning

confidence: 99%

TLR9: an important molecule in the fight against hepatitis B virus

Shahrakyvahed

Sanchooli

Sanadgol

et al. 2014

Postgraduate Medical Journal

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Hepatitis B virus (HBV) is the most prevalent infectious agent that can induce severe liver disease. Patients infected with long-term HBV, including chronic, asymptomatic and occult forms, cannot clear HBV from infected hepatocytes completely. It is not clear why some people can clear the infection while others cannot. Furthermore, the main mechanisms responsible for progression of the infections are not fully understood. It has been hypothesised that differences in genetic and immunological parameters between patients and subjects who successfully clear HBV infections are responsible for inducing the long-term forms of the infection. Previous investigations showed that Toll-like receptors (TLRs) play important roles in immune responses, especially innate immunity, against viral infections, including hepatitis B. TLR9 detects intracellular viral dsDNA, which results in the activation of an immune response against HBV. However, defects in this system may result in an attenuated response ultimately leading to long-term HBV infections. Targeting the defects in TLR9 or reactivating the downstream pathways that are normally switched on by TLR9 in response to HBV infection is a new approach to the treatment of long-term HBV infection. However, the pathways and defects seen in patients with long-term HBV need to be thoroughly explored before therapeutics can be applied in the clinical setting. Furthermore, the apparently multigenic nature of long-term HBV infection suggests that treatment of patients may need to be personalised.

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Toll‐like receptors and their adaptors are regulated in macrophages after phagocytosis of lipopolysaccharide‐coated titanium particles

Cited by 62 publications

References 45 publications

Lipoteichoic acid modulates inflammatory response in macrophages after phagocytosis of titanium particles through Toll‐like receptor 2 cascade and inflammasomes

Lipoteichoic acid modulates inflammatory response in macrophages after phagocytosis of titanium particles through Toll‐like receptor 2 cascade and inflammasomes

Interaction of materials and biology in total joint replacement – successes, challenges and future directions

TLR9: an important molecule in the fight against hepatitis B virus

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