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Propionibacterium acnes induces discogenic low back pain via stimulating nucleus pulposus cells to secrete pro-algesic factor of IL-8/CINC-1 through TLR2–NF-κB p65 pathway

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Abstract

Latent infection of Propionibacterium acnes was considered as a new pathogeny for low back pain (LBP); however, there is no credible animal evidence or mechanism hypothesis. This study proved that P. acnes is a causative pathogen of bacteria-induced LBP and investigated its underlying mechanism. For this, P. acnes was firstly identified in patients’ degenerated intervertebral disc (IVDs) samples. The results of patients’ Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ), Japanese Orthopaedic Association (JOA), and Oswestry Disability Index (ODI) scores indicated that P. acnes-positive patients showed more severe LBP and physical disability. Then, a P. acnes-inoculated lumbar IVDs model was established in rats. The results of paw/foot withdrawal threshold and qRT-PCR indicated that P. acnes-inoculated rats had obvious LBP in behavioral evaluation and over-expression of substance P (SP) and calcitonin gene-related peptide (CGRP) in IVDs. Subsequently, enzyme-linked immunosorbent assay (ELISA) results demonstrated that increased expression of IL-8 or CINC-1 (the homolog of IL-8 in rats) in the P. acnes-positive IVDs of human and rats. The CINC-1 injected animal model proved that the cytokines were able to induce LBP. Finally, the co-culture experiments showed that nucleus pulposus cells (NPCs) were able to respond to P. acnes and secreted IL-8/CINC-1 via TLR-2/NF-κB p65 pathway. In conclusion, P. acnes had strong association with LBP by stimulating NPCs to secrete pro-algesic factor of IL-8/CINC-1 via TLR2/NF-κBp65 pathway. The finding may provide a promising alternative therapy strategy for LBP in clinical.

Key messages

  • Patients with P. acnes-positive IVDs tended to have more severe LBP, physical disability, and increased IL-8 expressions.

  • P. acnes can induce LBP via IL-8/CINC-1 in IVDs.

  • P. acnes stimulate the NPCs to secrete pro-algesic factor of IL-8/CINC-1 via TLR2/NF-κBp65 pathway.

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Funding

This work was supported by grants from the Science and Technology Commission of Shanghai Municipality, Shanghai, China (No. 15DZ1942604); grants from the Shanghai Bureau of Health, Shanghai, China (Nos. 20164Y0132 and 20124294); the Shanghai Sailing Program, Shanghai, China (No. 16YF1410100); the National Natural Science fund, China (NSFC No. 81702188), and the Science and Technology Bureau of Kunshan, Kunshan, China (No. KS1547).

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Author notes

  1. Yucheng Jiao and Ye Yuan contributed equally to this work.

Authors and Affiliations

  1. Department of Orthopedics, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, 197 Ruijin Er Road, Shanghai, 200025, China

    Yucheng Jiao, Ye Yuan, Yazhou Lin, Wenjian Wu, Zhe Chen & Peng Cao

  2. Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases with Integrated Chinese-Western Medicine, Shanghai Institute of Traumatology and Orthopedics, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, 197 Ruijin Er Road, Shanghai, 200025, China

    Yucheng Jiao, Yazhou Lin, Changwei Li, Zhe Chen & Peng Cao

  3. Department of Orthopedics, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, 102218, China

    Ye Yuan

  4. Department of Orthopedic Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200092, China

    Zezhu Zhou

  5. Department of Orthopedics, Ruijin Hospital North, School of Medicine, Shanghai Jiaotong University, Shanghai, 201800, China

    Yuehuan Zheng

  6. Kunshan Hospital of Traditional Chinese medicine, Kunshan, 215300, China

    Guoqing Tang & Yong Chen

  7. Department of Medical Microbiology and Parasitology, School of Medicine, Shanghai Jiaotong University, Shanghai, 200025, China

    Jiaqi Xiao

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  1. Yucheng Jiao
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  2. Ye Yuan
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  10. Changwei Li
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  11. Zhe Chen
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  12. Peng Cao
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Corresponding authors

Correspondence to Changwei Li, Zhe Chen or Peng Cao.

Ethics declarations

The study was approved by the Institutional Review Board of Shanghai Ruijin Hospital (Ethics Committee Reference Number: 2013-60) and every participant signed an informed consent form. All animal experiments were performed in accordance with the protocol approved by the Shanghai Jiao Tong University (SJTU) Animal Care and Use Committee [IACUC protocol number: SYXK (Shanghai) 2011-0113] and in accordance with the Ministry of Science and Technology of the People’s Republic of China Animal Care guidelines.

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The authors declare that they have no competing interests.

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Jiao, Y., Yuan, Y., Lin, Y. et al. Propionibacterium acnes induces discogenic low back pain via stimulating nucleus pulposus cells to secrete pro-algesic factor of IL-8/CINC-1 through TLR2–NF-κB p65 pathway. J Mol Med 97, 25–35 (2019). https://doi.org/10.1007/s00109-018-1712-z

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  • DOI: https://doi.org/10.1007/s00109-018-1712-z

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