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dc.contributor.advisor Setton, Lori A en_US
dc.contributor.author Sinclair, SM
dc.contributor.author Shamji, MF
dc.contributor.author Chen, J
dc.contributor.author Jing, L
dc.contributor.author Richardson, WJ
dc.contributor.author Brown, CR
dc.contributor.author Fitch, RD
dc.contributor.author Setton, LA
dc.coverage.spatial United States
dc.date.accessioned 2011-01-06T20:46:06Z
dc.date.issued 2011-07-01
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/21217452
dc.identifier.citation Spine (Phila Pa 1976), 2011, 36 (15), pp. 1190 - 1196
dc.identifier.uri http://hdl.handle.net/10161/3155
dc.description Thesis en_US
dc.description.abstract STUDY DESIGN: The inflammatory responses of primary human intervertebral disc (IVD) cells to tumor necrosis factor α (TNF-α) and an antagonist were evaluated in vitro. OBJECTIVE: To investigate an ability for soluble TNF receptor type II (sTNFRII) to antagonize TNF-α-induced inflammatory events in primary human IVD cells in vitro. SUMMARY OF BACKGROUND DATA: TNF-α is a known mediator of inflammation and pain associated with radiculopathy and IVD degeneration. sTNFRs and their analogues are of interest for the clinical treatment of these IVD pathologies, although information on the effects of sTNFR on human IVD cells remains unknown. METHODS: IVD cells were isolated from surgical tissues procured from 15 patients and cultured with or without 1.4 nmol/L TNF-α (25 ng/mL). Treatment groups were coincubated with varying doses of sTNFRII (12.5-100 nmol/L). Nitric oxide (NO), prostaglandin E₂ (PGE₂), and interleukin-6 (IL6) levels in media were quantified to characterize the inflammatory phenotype of the IVD cells. RESULTS: Across all patients, TNF-α induced large, statistically significant increases in NO, PGE₂, and IL6 secretion from IVD cells compared with controls (60-, 112-, and 4-fold increases, respectively; P < 0.0001). Coincubation of TNF-α with nanomolar doses of sTNFRII significantly attenuated the secretion of NO and PGE₂ in a dose-dependent manner, whereas IL6 levels were unchanged. Mean IC₅₀ values for NO and PGE₂ were found to be 35.1 and 20.5 nmol/L, respectively. CONCLUSION: Nanomolar concentrations of sTNFRII were able to significantly attenuate the effects of TNF-α on primary human IVD cells in vitro. These results suggest this sTNFR to be a potent TNF antagonist with potential to attenuate inflammation in IVD pathology.
dc.format.extent 1190 - 1196
dc.language ENG
dc.relation.ispartof Spine (Phila Pa 1976)
dc.relation.isversionof 10.1097/BRS.0b013e3181ebdb43
dc.subject Adolescent
dc.subject Adult
dc.subject Aged
dc.subject Cells, Cultured
dc.subject Dinoprostone
dc.subject Dose-Response Relationship, Drug
dc.subject Humans
dc.subject Interleukin-6
dc.subject Intervertebral Disc
dc.subject Intervertebral Disc Degeneration
dc.subject Middle Aged
dc.subject Nitric Oxide
dc.subject Receptors, Tumor Necrosis Factor, Type II
dc.subject Tumor Necrosis Factor-alpha
dc.subject Young Adult
dc.title Attenuation of inflammatory events in human intervertebral disc cells with a tumor necrosis factor antagonist.
dc.type Journal Article
dc.department Biomedical Engineering en_US
duke.embargo.months 12 en_US
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/21217452
pubs.issue 15
pubs.organisational-group /Duke
pubs.organisational-group /Duke/Institutes and Provost's Academic Units
pubs.organisational-group /Duke/Institutes and Provost's Academic Units/University Institutes and Centers
pubs.organisational-group /Duke/Institutes and Provost's Academic Units/University Institutes and Centers/Duke Institute for Brain Sciences
pubs.organisational-group /Duke/Pratt School of Engineering
pubs.organisational-group /Duke/Pratt School of Engineering/Biomedical Engineering
pubs.organisational-group /Duke/School of Medicine
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Orthopaedics
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Pediatrics
pubs.publication-status Published
pubs.volume 36
dc.identifier.eissn 1528-1159

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