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SPHK-2 Promotes the Particle-Induced Inflammation of RAW264.7 by Maintaining Consistent Expression of TNF-α and IL-6

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Abstract

Aseptic implant loosening is a devastating long-term complication of total joint arthroplasty. It is mainly initiated by the interaction of wear debris and macrophages. However, how does the chronic inflammation persist and how to stop it is poorly understood. Sphingosine kinases (SPHKs) are an essential feature of immunosuppressive M2 polarisation in macrophages and a promoter for chronic inflammation. In this study, RAW 264.7 macrophages were exposed to stimulation with titanium particles (0.1 mg/ml), and the subsequent expression of SPHKs and pro-inflammatory cytokines was evaluated. The effect of inhibitors of SPHKs (FTY720, PF543, and ABC294640) on titanium particle-challenged macrophages was analysed. As for results, the amount of sphingosine kinase (SPHK)-1 and SPHK-2 in RAW264.7 macrophages increased in the presence of titanium particles in a time-dependent manner. Two inhibitors of SPHKs (FTY720 and ABC294640) suppressed titanium particle-induced tumour necrosis factor (TNF)-α and interleukin (IL)-6 production in RAW264.7 macrophages. These findings suggest that persistent stimulation with titanium particles may lead to a consistent release of TNF-α and IL-6 via SPHK-2 activity, which may lead to aseptic implant loosening. Appropriate regulation of SPHK-2 may serve as a potential new strategy in the treatment of aseptic implant loosening.

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Acknowledgments

We thank Xiujian Lan and Xuanhong Zhang (Department of Medical Science Experimentation Center, Sun Yat-sen University) for technical support.

Funding

This study was funded by the National Natural Science Foundation of China (grant No. 81672149, No. 81171710) and the Natural Science Foundation of Guangdong Province (No. 2015A030311004).

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Author notes

  1. Guangpu Yang and Minghui Gu contributed equally to this work.

Authors and Affiliations

  1. Department of Joint Surgery, The First Affiliated Hospital, Sun Yat-Sen University, No. 58, Zhongshan Rd. 2, Guangzhou, 510080, China

    Guangpu Yang, Minghui Gu, Weishen Chen, Yinbo Xiao, Weiming Lai, Guoyan Xian, Ziji Zhang & Puyi Sheng

  2. Department of Joint Surgery, The First Hospital of Baoan District, Shenzhen, China

    Wenhua Liu

  3. Department of Orthopedic and Traumatology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China

    Haixing Wang

  4. Department of Anatomy and Cell Biology, Penn Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Ziqing Li

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  1. Guangpu Yang
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Yang, G., Gu, M., Chen, W. et al. SPHK-2 Promotes the Particle-Induced Inflammation of RAW264.7 by Maintaining Consistent Expression of TNF-α and IL-6. Inflammation 41, 1498–1507 (2018). https://doi.org/10.1007/s10753-018-0795-6

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