2. Academic Validation
  3. 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

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 (Berl). 2019 Jan;97(1):25-35. doi: 10.1007/s00109-018-1712-z.
Yucheng Jiao 1 2,  Ye Yuan 1 3,  Yazhou Lin 1 2,  Zezhu Zhou 4,  Yuehuan Zheng 5,  Wenjian Wu 1,  Guoqing Tang 6,  Yong Chen 6,  Jiaqi Xiao 7,  Changwei Li 8,  Zhe Chen 9 10,  Peng Cao 11 12
Affiliations

Affiliations

  • 1 Department of Orthopedics, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, 197 Ruijin Er Road, Shanghai, 200025, China.
  • 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.
  • 3 Department of Orthopedics, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, 102218, China.
  • 4 Department of Orthopedic Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200092, China.
  • 5 Department of Orthopedics, Ruijin Hospital North, School of Medicine, Shanghai Jiaotong University, Shanghai, 201800, China.
  • 6 Kunshan Hospital of Traditional Chinese medicine, Kunshan, 215300, China.
  • 7 Department of Medical Microbiology and Parasitology, School of Medicine, Shanghai Jiaotong University, Shanghai, 200025, China.
  • 8 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. changwei393331@163.com.
  • 9 Department of Orthopedics, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, 197 Ruijin Er Road, Shanghai, 200025, China. drchenzhe@live.com.
  • 10 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. drchenzhe@live.com.
  • 11 Department of Orthopedics, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, 197 Ruijin Er Road, Shanghai, 200025, China. dr_caopeng8@163.com.
  • 12 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. dr_caopeng8@163.com.
PMID: 30397790 DOI: 10.1007/s00109-018-1712-z
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.

Keywords

Interleukin-8; Intervertebral disc; Low back pain; Nucleus pulposus cells; Propionibacterium acnes.

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