Wear particles promote endotoxin tolerance in macrophages by inducing interleukin‐1 receptor‐associated kinase‐M expression

Zhang, Yangchun; Yu, Si; Xiao, Jianlin; Hou, Changhe; Li, Ziqing; Zhang, Ziji; Zhai, Qiyi; Lehto, Matti; Konttinen, Yrjö T.; Sheng, Puyi

doi:10.1002/jbm.a.34740

Cited by 4 publications

(12 citation statements)

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“…The presence of endotoxins was <0.01 endotoxin units/mL, confirming the effectiveness of the cleaning procedure (11). The particles were maintained in PBS 25 mg/mL at 4 °C, and the solution was agitated for 20 min prior to each use (13).…”

Section: Titanium Particlesmentioning

confidence: 70%

Pro-inflammatory Analysis of Macrophages in Contact with Titanium Particles and Porphyromonas gingivalis

et al. 2017

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During insertion of titanium dental implants, particles may shear from the implant to the periimplant region causing osteolysis, and their association with bacteria can exacerbate the inflammatory reaction. However, the association of a high invasive bacterium from the oral cavity, Porphyromonas gingivalis (Pg), and titanium particles remains unknown. This study evaluated pro-inflammatory reaction of human macrophages in contact with micro and nanoparticles of titanium associated with Porphyromonas gingivalis lipopolysaccharide (PgLPS). THP-1 cell were used and treated for 12, 24 and 48 h following 6 groups: Control(C), PgLPS (L); Microparticles (M); Nanoparticles (N); PgLPS and microparticles (LM); PgLPS and nanoparticles (LN). The following assays were carried out: i) cell viability using MTS, ii) cell morphology by SEM and iii) expression of tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) by qRT-PCR and ELISA. For statistics two-way ANOVA followed by Tukey's test was used (p<0.05). After treatment, cells presented similar viability and morphology demonstrating that the treatments were not able to induce cell death. Gene expression was significantly higher for TNF-α and IL1-β after 12 h, and for IL-6 after 24 h in the N and LN groups. Cytokine production over time was an ascending curve for TNF-α with the peak at 48 h and IL1-β and IL-6 had a straight line among the time points, although cells from N group presented a significant production of IL-6 at 48 h. In conclusion, these results suggest that titanium nanoparticles stimulate stronger pro-inflammatory response in macrophages, independent of their association with LPS from P.gingivalis.

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Section: Titanium Particlesmentioning

confidence: 70%

Pro-inflammatory Analysis of Macrophages in Contact with Titanium Particles and Porphyromonas gingivalis

et al. 2017

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“…Implant loosening is the most common complication in the long-term follow-up of joint arthroplasty, which is mediated by acute and chronic inflammation produced chiefly by macrophages stimulated by prosthesis-derived wear particles. 1 – 5 The causes of loosening are complicated, and the implant loosening is mainly classified into two different categories, namely aseptic and septic implant loosening. Septic implant loosening is deemed to be caused by deep prosthesis-associated infections, while the aseptic is thought to be due to inflammatory cytokines, mostly from particle-stimulated macrophages.…”

Section: Introductionmentioning

confidence: 99%

“… 5 , 8 – 11 It was also demonstrated that, from in vivo and in vitro studies, pure wear particles cannot lead to substantial and effective inflammatory osteolysis causing implant loosening, which merely accounted for a small percentage of cases. 4 , 12 – 15 Osteoclastogenesis, as has been found in suppurative arthritis and prosthesis-related pyogenic infections, is seemingly more efficaciously provoked by pathogenic microorganisms, bacterial components and PAMP, all of which adhere to the superficies of implants and eventually wear particles. 3 , 4 , 13 , 16 These stimuli activate a series of inflammatory cytokines and cause prosthetic loosening.…”

Section: Introductionmentioning

confidence: 99%

“… 4 , 12 – 15 Osteoclastogenesis, as has been found in suppurative arthritis and prosthesis-related pyogenic infections, is seemingly more efficaciously provoked by pathogenic microorganisms, bacterial components and PAMP, all of which adhere to the superficies of implants and eventually wear particles. 3 , 4 , 13 , 16 These stimuli activate a series of inflammatory cytokines and cause prosthetic loosening. 4 , 13 , 17 Hence, adhered microorganisms and their components are affirmatively participating in loosening.…”

Section: Introductionmentioning

confidence: 99%

“… 3 , 4 , 13 , 16 These stimuli activate a series of inflammatory cytokines and cause prosthetic loosening. 4 , 13 , 17 Hence, adhered microorganisms and their components are affirmatively participating in loosening.…”

Section: Introductionmentioning

confidence: 99%

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IRAK-4 in macrophages contributes to inflammatory osteolysis of wear particles around loosened hip implants

et al. 2021

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TLRs recognizing PAMPS play a role in local immunity and participate in implant-associated loosening. TLR-mediated signaling is primarily regulated by IL-1 receptor associated kinase-M (IRAK-M) negatively and IRAK-4 positively. Our previous studies have proved that wear particles promote endotoxin tolerance in macrophages by inducing IRAK-M. However, whether IRAK-4 is involved in inflammatory osteolysis of wear particles basically, and the specific mechanism of IRAK-4 around loosened hip implants, is still unclear. IRAK-4 was studied in the interface membranes from patients in vivo and in particle-stimulated macrophages to clarify its role. Also, IL-1β and TNF-α levels were measured after particle and LPS stimulation in macrophages with or without IRAK-4 silenced by siRNA. Our results showed that the interface membranes around aseptic and septic loosened prosthesis expressed more IRAK-4 compared with membranes from osteoarthritic patients. IRAK-4 in macrophages increased upon particle and LPS stimulation. In the former, IL-1β and TNF-α levels were lower compared with those of LPS stimulation, and IRAK-4 siRNA could suppress production of pro-inflammatory cytokines. These findings suggest that besides IRAK-M, IRAK-4 also plays an important role in the local inflammatory reaction and contributes to prosthesis loosening.

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Recent advances in endotoxin tolerance

Liú

Cao

Zhou

et al. 2018

J of Cellular Biochemistry

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Endotoxin tolerance is defined as a reduced capacity of a cell to respond endotoxin (lipopolysaccharide, LPS) challenge after an initial encounter with endotoxin in advance. The body becomes tolerant to subsequent challenge with a lethal dose of endotoxin and cytokines release and cell/tissue damage induced by inflammatory reaction are significantly reduced in the state of endotoxin tolerance. The main characteristics of endotoxin tolerance are downregulation of inflammatory mediators such as tumor necrosis factor α (TNF‐α), interleukin‐1β (IL‐1β), and C‐X‐C motif chemokine 10 (CXCL10) and upregulation of anti‐inflammatory cytokines such as IL‐10 and transforming growth factor β (TGF‐β). Therefore, endotoxin tolerance is often regarded as the regulatory mechanism of the host against excessive inflammation. Endotoxin tolerance is a complex pathophysiological process and involved in multiple cellular signal pathways, receptor alterations, and biological molecules. However, the exact mechanism remains elusive up to date. To better understand the underlying cellular and molecular mechanisms of endotoxin tolerance, it is crucial to investigate the comprehensive cellular signal pathways, signaling proteins, cell surface molecules, proinflammatory and anti‐inflammatory cytokines, and other mediators. Endotoxin tolerance plays an important role in reducing the mortality of sepsis, endotoxin shock, and other endotoxin‐related diseases. Recent reports indicated that endotoxin tolerance is also related to other diseases such as cystic fibrosis, acute coronary syndrome, liver ischemia‐reperfusion injury, and cancer. The aim of this review is to discuss the recent advances in endotoxin tolerance mainly based on the cellular and molecular mechanisms by outline the current state of the knowledge of the involvement of the toll‐like receptor 4 (TLR4) signaling pathways, negative regulate factor, microRNAs, apoptosis, chromatin modification, and gene reprogramming of immune cells in endotoxin tolerance. We hope to provide a new idea and scientific basis for the rational treatment of endotoxin‐related diseases such as endotoxemia, sepsis, and endotoxin shock clinically.

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Wear particles promote endotoxin tolerance in macrophages by inducing interleukin‐1 receptor‐associated kinase‐M expression

Cited by 4 publications

References 0 publications

Pro-inflammatory Analysis of Macrophages in Contact with Titanium Particles and Porphyromonas gingivalis

Pro-inflammatory Analysis of Macrophages in Contact with Titanium Particles and Porphyromonas gingivalis

IRAK-4 in macrophages contributes to inflammatory osteolysis of wear particles around loosened hip implants

Recent advances in endotoxin tolerance

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