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Do mechanical strain and TNF-α interact to amplify pro-inflammatory cytokine production in human annulus fibrosus cells?
| Content Provider | Scilit |
|---|---|
| Author | Likhitpanichkul, Morakot Torre, Olivia M. Gruen, Jadry Walter, Benjamin A. Hecht, Andrew C. Iatridis, James C. |
| Copyright Year | 2016 |
| Description | Journal: Journal of biomechanics During intervertebral disc (IVD) injury and degeneration, annulus fibrosus (AF) cells experience large mechanical strains in a pro-inflammatory milieu. We hypothesized that TNF-α, an initiator of IVD inflammation, modifies AF cell mechanobiology via cytoskeletal changes, and interacts with mechanical strain to enhance pro-inflammatory cytokine production. Human AF cells (N=5, Thompson grades 2-4) were stretched uniaxially on collagen-I coated chambers to 0%, 5% (physiological) or 15% (pathologic) strains at 0.5Hz for 24h under hypoxic conditions with or without TNF-α (10ng/mL). AF cells were treated with anti-TNF-α and anti-IL-6. ELISA assessed IL-1β, IL-6, and IL-8 production and immunocytochemistry measured F-actin, vinculin and α-tubulin in AF cells. TNF-α significantly increased AF cell pro-inflammatory cytokine production compared to basal conditions (IL-1β:2.0±1.4-84.0±77.3, IL-6:10.6±9.9-280.9±214.1, IL-8:23.9±26.0-5125.1±4170.8pg/ml for basal and TNF-α treatment, respectively) as expected, but mechanical strain did not. Pathologic strain in combination with TNF-α increased IL-1β, and IL-8 but not IL-6 production of AF cells. TNF-α treatment altered F-actin and α-tubulin in AF cells, suggestive of altered cytoskeletal stiffness. Anti-TNF-α (infliximab) significantly inhibited pro-inflammatory cytokine production while anti-IL-6 (atlizumab) did not. In conclusion, TNF-α altered AF cell mechanobiology with cytoskeletal remodeling that potentially sensitized AF cells to mechanical strain and increased TNF-α-induced pro-inflammatory cytokine production. Results suggest an interaction between TNF-α and mechanical strain and future mechanistic studies are required to validate these observations. |
| Related Links | http://europepmc.org/articles/pmc4913356?pdf=render https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4913356/pdf |
| Ending Page | 1220 |
| Page Count | 7 |
| Starting Page | 1214 |
| ISSN | 00219290 |
| e-ISSN | 18732380 |
| DOI | 10.1016/j.jbiomech.2016.02.029 |
| Journal | Journal of biomechanics |
| Issue Number | 7 |
| Volume Number | 49 |
| Language | English |
| Publisher | Elsevier BV |
| Publisher Date | 2016-05-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Journal of biomechanics Intervertebral Disc Degeneration Mechanical Stretch Mechanotransduction |
| Content Type | Text |
| Resource Type | Article |
| Subject | Orthopedics and Sports Medicine Rehabilitation Biophysics Sports Science Biomedical Engineering |
