Ma, Junxuan; Häne, Surya; Eglauf, Janick; Pfannkuche, Judith; Soubrier, Astrid; Li, Zhen; Peroglio, Marianna; Hoppe, Sven; Benneker, Lorin; Lang, Gernot; Wangler, Sebastian; Alini, Mauro; Creemers, Laura B; Grad, Sibylle; Häckel, Sonja (2023). Celecoxib alleviates nociceptor sensitization mediated by interleukin-1beta-primed annulus fibrosus cells. European spine journal, 32(6), pp. 2048-2058. Springer 10.1007/s00586-023-07672-x
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PURPOSE
This study aims to analyze the effect of pro-inflammatory cytokine-stimulated human annulus fibrosus cells (hAFCs) on the sensitization of dorsal root ganglion (DRG) cells. We further hypothesized that celecoxib (cxb) could inhibit hAFCs-induced DRG sensitization.
METHODS
hAFCs from spinal trauma patients were stimulated with TNF-α or IL-1β. Cxb was added on day 2. On day 4, the expression of pro-inflammatory and neurotrophic genes was evaluated using RT-qPCR. Levels of prostaglandin E2 (PGE-2), IL-8, and IL-6 were measured in the conditioned medium (CM) using ELISA. hAFCs CM was then applied to stimulate the DRG cell line (ND7/23) for 6 days. Then, calcium imaging (Fluo4) was performed to evaluate DRG cell sensitization. Both spontaneous and bradykinin-stimulated (0.5 μM) calcium responses were analyzed. The effects on primary bovine DRG cell culture were performed in parallel to the DRG cell line model.
RESULTS
IL-1ß stimulation significantly enhanced the release of PGE-2 in hAFCs CM, while this increase was completely suppressed by 10 µM cxb. hAFCs revealed elevated IL-6 and IL-8 release following TNF-α and IL-1β treatment, though cxb did not alter this. The effect of hAFCs CM on DRG cell sensitization was influenced by adding cxb to hAFCs; both the DRG cell line and primary bovine DRG nociceptors showed a lower sensitivity to bradykinin stimulation.
CONCLUSION
Cxb can inhibit PGE-2 production in hAFCs in an IL-1β-induced pro-inflammatory in vitro environment. The cxb applied to the hAFCs also reduces the sensitization of DRG nociceptors that are stimulated by the hAFCs CM.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Department of Orthopaedic, Plastic and Hand Surgery (DOPH) > Clinic of Orthopaedic Surgery |
UniBE Contributor: |
Hoppe, Sven, Benneker, Lorin Michael, Wangler, Sebastian, Häckel, Sonja |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
1432-0932 |
Publisher: |
Springer |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
19 Apr 2023 10:22 |
Last Modified: |
02 Jun 2023 00:15 |
Publisher DOI: |
10.1007/s00586-023-07672-x |
PubMed ID: |
37071156 |
Uncontrolled Keywords: |
3R principle Annulus fibrosus COX-2 Celecoxib Cyclooxygenase 2 inhibitor DRG Dorsal root ganglion In vitro model Inflammatory cytokine Intervertebral disk |
BORIS DOI: |
10.48350/181834 |
URI: |
https://boris.unibe.ch/id/eprint/181834 |
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