Positive feedback loop of interleukin-1β upregulating production of inflammatory mediators in human intervertebral disc cells in vitro

Kotaro Jimbo M.D.1, Jin Soo Park M.D., Ph.D.1, Kimiaki Yokosuka M.D.1, Kimiaki Sato M.D., Ph.D.1, and Kensei Nagata M.D., Ph.D.1
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  • 1 Department of Orthopaedic Surgery, Kurume University School of Medicine, Fukuoka, Japan
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Object. Interleukin-1β (IL-1β) induces neurological symptoms in intervertebral disc herniation (IDH). Recently, the existence of a positive feedback loop of IL-1β, which encourages an inflammatory reaction or degeneration in the cells of tendon, has been reported. The authors hypothesized that there is a positive feedback loop of IL-1β in the cells of IDH.

Methods. Eight human intervertebral disc specimens were harvested during spinal surgery for lumbar disc herniation. The cells were stimulated in serum-free medium with or without exogenous IL-1β. The messenger RNA (mRNA) was extracted for reverse-transcription polymerase chain reaction (PCR) and real-time PCR to quantify the mRNA of endogenous IL-1β, IL-6, cyclooxygenase-2 (COX-2), and matrix metalloproteinases (MMPs). The cells were then stimulated in serum-free medium with or without exogenous IL-1β, and then exogenous IL-1β was removed. After 2, 4, and 6 days, the medium was collected, and enzyme-linked immunosorbent assay was used to measure the protein concentration of endogenous IL-1β. The mRNA expressions of endogenous IL-1β, IL-6, COX-2, and MMPs were increased significantly depending on the concentration of exogenous IL-1β. The protein concentration of endogenous IL-1β was increased over time.

Conclusions. There was a positive feedback loop of IL-1β in the cells of IDH. Furthermore, the productions of IL-6, COX-2, MMP-1, and MMP-3 were upregulated as a result of the increasing concentration of IL-1β in a positive feedback loop of IL-1β. The authors concluded that this positive feedback loop of IL-1β upregulated the production of mediators and thus can cause cessation of symptoms in IDH.

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Contributor Notes

Address reprint requests to: Jin Soo Park, M.D., Ph.D., Department of Orthopaedic Surgery, Kurume University School of Medicine, 67 Asahimachi, Kurume, Fukuoka 830-0011, Japan. email: jisopark@hotmail.com.
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