Toll-like receptor 4 signaling pathway mediates proinflammatory immune response to cobalt-alloy particles

Potnis, Pushya A.; Dutta, Debargh; Wood, Steven C.

doi:10.1016/j.cellimm.2013.04.003

Cited by 63 publications

(41 citation statements)

References 44 publications

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“…TLR4 signaling ultimately results in the reduction of cytokine levels and activation of NF-κB (the transcription factor) [34]. Additionally, one study showed that the TLR4 signaling pathway mediated the proinflammatory immune response to cobalt-alloy particles [35]. The level of the receptor activator of NF-κB was apparently increased in samples from patients with peri-implantitis compared with healthy implants [36].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of NF-κB by Pyrrolidine Dithiocarbamate Prevents the Inflammatory Response in a Ligature-Induced Peri-Implantitis Model: A Canine Study

Jiang²,

Wang

et al. 2018

Cell Physiol Biochem

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Background/Aims: The roles of toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-κB) in peri-implantitis are unclear. Here, we used a canine model of peri-implantitis to explore the effects of inhibiting NF-κB with pyrrolidine dithiocarbamate (PDTC) on the inflammatory response in ligature-induced peri-implantitis. Methods: After successfully establishing the peri-implantitis model, beagles were randomly assigned to normal, model or PDTC groups. ELISA tests were used to determine the levels of interleukin (IL)-1, IL-6, IL-8 and tumor necrosis factor alpha (TNF-α). Immunohistochemistry was employed to assess the expression of NF-κB p65. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to determine the mRNA levels of TLR4 and NF-κB p65, and western blot analysis was used to measure the protein levels of TLR4 in periodontal tissues from each group. Periodontal ligament fibroblasts (PDLFs) were cultured and subsequently classified into PDLF normal, PDLF model, PDLF LPS, PDLF PDTC, and PDLF LPS + PDTC groups. An immunofluorescence assay was used to measure the expression level of NF-κB p65. The CCK-8 assay and flow cytometry were performed to evaluate cell proliferation and apoptosis. Results: The in vitro results indicated that NF-κB p65 and TLR4 were upregulated in canine periodontal tissues, and PDTC could suppress the expression levels of NF-κB p65 and TLR4. Inflammation could increase TLR4 protein expression in canine periodontal tissue, and PDTC could inhibit the inflammation-induced increase in TLR4 protein expression. These results revealed that PDTC could reverse the LPS-induced increases in the levels of IL-1, IL-6, IL-8 and TNF-α. In vivo, the results demonstrated that PDTC inhibited the LPS-induced NF-κB p65 upregulation, and PDTC could reverse the inhibitory effect of the PDLF model + LPS on the proliferation of periodontal fibroblasts. The results also showed that in the PDLF model, LPS promoted PDLF apoptosis by inducing implant periodontitis in canines, but PDTC inhibited the PDLF apoptosis and relieved implant periodontitis in canines. Conclusion: Based on our results, we concluded that PDTC can inhibit the expression of NF-κB and alleviate the inflammatory response induced by LPS, thereby preventing periodontal inflammation and reducing the development of peri-implantitis.

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Section: Discussionmentioning

confidence: 99%

Inhibition of NF-κB by Pyrrolidine Dithiocarbamate Prevents the Inflammatory Response in a Ligature-Induced Peri-Implantitis Model: A Canine Study

Jiang²,

Wang

et al. 2018

Cell Physiol Biochem

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“…Thus, nickel has intrinsic adjuvant properties in humans that promote sensitization of T cells. Similarly, cobalt and palladium ions also induce TLR4-dependent signaling [16,17]. …”

Section: Recognition Of Metals By the Innate Immune Systemmentioning

confidence: 99%

Interplay of innate and adaptive immunity in metal-induced hypersensitivity

McKee

Fontenot

2016

Current Opinion in Immunology

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Metal-induced hypersensitivity is driven by T cell sensitization to metal ions. Recent advances in our understanding of the complex interactions between innate and adaptive immunity have expanded our knowledge of the pathogenesis of these diseases. Metals activate the innate immune system through direct binding to pathogen recognition receptors, activation of the inflammasome, or the induction of cellular death and release of alarmins. Certain metals can serve as adjuvants, promoting dendritic cell activation and migration as well as antigen presentation to metal-specific T cells. These T cells can recognize metals as haptens or as altered MHC-peptide complexes. The ability of metals to create these neoantigens emphasizes the similarity between metal-induced hypersensitivity and autoimmunity.

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“…Moreover, it has recently been reported that human TLR4 can be activated by cobalt or nickel ions [88,110], both of which can be released by corrosion of cobaltchromium implants [39]. Functional studies have shown that deletion of TLR2 and/or TLR4 in murine systems substantially reduces the in vitro and in vivo responses to titanium [8,37], UHMWPE [40], cobalt-chromium [85], and hydroxyapatite [34] particles. Moreover, similar results have also been obtained for deletion of the myeloid differentiation primary response gene (MyD88) with both PMMA and cobalt-chromium particles [82,85].…”

Section: Toll-like Receptorsmentioning

confidence: 99%

“…Functional studies have shown that deletion of TLR2 and/or TLR4 in murine systems substantially reduces the in vitro and in vivo responses to titanium [8,37], UHMWPE [40], cobalt-chromium [85], and hydroxyapatite [34] particles. Moreover, similar results have also been obtained for deletion of the myeloid differentiation primary response gene (MyD88) with both PMMA and cobalt-chromium particles [82,85]. MyD88 is an adaptor protein involved in signaling by most TLRs and members of the IL-1 receptor family [51,79].…”

Section: Toll-like Receptorsmentioning

confidence: 99%

Do Genetic Susceptibility, Toll-like Receptors, and Pathogen-associated Molecular Patterns Modulate the Effects of Wear?

Greenfield

2014

Clin Orthop Relat Res

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Background Overwhelming evidence supports the concept that wear particles are the primary initiator of aseptic loosening of orthopaedic implants. It is likely, however, that other factors modulate the biologic response to wear particles. This review focuses on three potential other factors: genetic susceptibility, Toll-like receptors (TLRs), and bacterial pathogen-associated molecular patterns (PAMPs). Where Are We Now? Considerable evidence is emerging that both genetic susceptibility and TLR activation are important factors that modulate the biologic response to wear particles, but it remains controversial whether bacterial PAMPs also do so. Where Do We Need to Go? Detailed understanding of the roles of these other factors may lead to identification of novel therapeutic targets for patients with aseptic loosening. How Do We Get There? Highest priority should be given to polymorphism replication studies with large numbers of patients and studies to replicate the reported correlation between bacterial biofilms and the severity of aseptic loosening.

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Toll-like receptor 4 signaling pathway mediates proinflammatory immune response to cobalt-alloy particles

Cited by 63 publications

References 44 publications

Inhibition of NF-κB by Pyrrolidine Dithiocarbamate Prevents the Inflammatory Response in a Ligature-Induced Peri-Implantitis Model: A Canine Study

Inhibition of NF-κB by Pyrrolidine Dithiocarbamate Prevents the Inflammatory Response in a Ligature-Induced Peri-Implantitis Model: A Canine Study

Interplay of innate and adaptive immunity in metal-induced hypersensitivity

Do Genetic Susceptibility, Toll-like Receptors, and Pathogen-associated Molecular Patterns Modulate the Effects of Wear?

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