FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / Cell Tissue Res / Tumour necrosis factor alpha, interleukin 1 beta and interfe...
Cell and tissue research2022; 391(3); 523-544; doi: 10.1007/s00441-022-03726-6

Tumour necrosis factor alpha, interleukin 1 beta and interferon gamma have detrimental effects on equine tenocytes that cannot be rescued by IL-1RA or mesenchymal stromal cell-derived factors.

Abstract: Tendon injuries occur commonly in both human and equine athletes, and poor tendon regeneration leads to functionally deficient scar tissue and an increased frequency of re-injury. Despite evidence suggesting inadequate resolution of inflammation leads to fibrotic healing, our understanding of the inflammatory pathways implicated in tendinopathy remains poorly understood, meaning successful targeted treatments are lacking. Here, we demonstrate IL-1β, TNFα and IFN-γ work synergistically to induce greater detrimental consequences for equine tenocytes than when used individually. This includes altering tendon associated and matrix metalloproteinase gene expression and impairing the cells' ability to contract a 3-D collagen gel, a culture technique which more closely resembles the in vivo environment. Moreover, these adverse effects cannot be rescued by direct suppression of IL-1β using IL-1RA or factors produced by BM-MSCs. Furthermore, we provide evidence that NF-κB, but not JNK, P38 MAPK or STAT 1, is translocated to the nucleus and able to bind to DNA in tenocytes following TNFα and IL-1β stimulation, suggesting this signalling cascade may be responsible for the adverse downstream consequences of these inflammatory cytokines. We suggest a superior approach for treatment of tendinopathy may therefore be to target specific signalling pathways such as NF-κB.
© 2022. The Author(s).
Get Full Text
Publication Date: 2022-12-22 PubMed ID: 36543895PubMed Central: PMC9974687DOI: 10.1007/s00441-022-03726-6Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research article explores the detrimental effects of certain inflammation markers on horse tendon cells and concludes that suppressing these markers is insufficient to mitigate their negative impact, suggesting that future treatments should focus on specific cellular pathways.

Research Objectives

  • The study aimed to better understand the inflammatory pathways involved in tendinopathy, a condition characterized by tenderness or pain in a tendon.
  • It focused on three inflammatory cytokines – interleukin 1 beta (IL-1β), tumor necrosis factor alpha (TNFα), and interferon gamma (IFN-γ) – which have been hypothesized to exacerbate tendinopathy.

Methods and Findings

  • To study the effects of these cytokines on equine tenocytes – the primary cells within tendons – researchers used a 3-D collagen gel culture technique, which mimics the in vivo environment more closely than traditional petri-dish based cultures.
  • It was found that these cytokines significantly altered gene expression related to tendons and matrix metalloproteinase. Additionally, they impaired the tenocytes’ ability to contract, which hampers the cells’ normal function.
  • Importantly, the study showed that IL-1β, TNF, and IFN-γ when used together had a far more detrimental impact than when used separately, indicating their synergistic negative effect on tenocytes.
  • The researchers also attempted to alleviate these adverse effects by using IL-1RA, a suppressor of IL-1β, and factors produced by bone marrow-derived mesenchymal stromal cells (BM-MSCs). However, they found that neither of these approaches could counter the negative impact.
  • Upon closer study of the signaling pathways activated by the cytokines, it was observed that NF-κB (a protein complex involved in cellular responses) but not JNK, P38 MAPK, or STAT 1 was translocated to the nucleus and able to bind to DNA in tenocytes. This suggests that the NF-κB signalling pathway may be driving the adverse effects of the inflammatory cytokines.

Implications and Recommendations

  • This study contributes to current knowledge on tendinopathy by revealing that traditional methods of suppressing inflammation may not be an effective strategy for treating the condition.
  • Instead, it suggests that a better approach might be to target specific cellular pathways, such as NF-κB, to mitigate the harmful effects of inflammatory cytokines.

Cite This Article

APA
Smith EJ, Beaumont RE, McClellan A, Sze C, Palomino Lago E, Hazelgrove L, Dudhia J, Smith RKW, Guest DJ. (2022). Tumour necrosis factor alpha, interleukin 1 beta and interferon gamma have detrimental effects on equine tenocytes that cannot be rescued by IL-1RA or mesenchymal stromal cell-derived factors. Cell Tissue Res, 391(3), 523-544. https://doi.org/10.1007/s00441-022-03726-6

Publication

Cell and tissue research
ISSN: 1432-0878
NlmUniqueID: 0417625
Country: Germany
Language: English
Volume: 391
Issue: 3
Pages: 523-544

Researcher Affiliations

Smith, Emily J
  • Department of Clinical Sciences and Services, The Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Herts, AL9 7TA, UK. ejsmith@rvc.ac.uk.
Beaumont, Ross E
  • Department of Clinical Sciences and Services, The Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Herts, AL9 7TA, UK.
McClellan, Alyce
  • Centre for Preventative Medicine, Animal Health Trust, Newmarket, Suffolk, CB8 7UU, UK.
Sze, Cheryl
  • Centre for Preventative Medicine, Animal Health Trust, Newmarket, Suffolk, CB8 7UU, UK.
Palomino Lago, Esther
  • Department of Clinical Sciences and Services, The Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Herts, AL9 7TA, UK.
Hazelgrove, Liberty
  • Department of Clinical Sciences and Services, The Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Herts, AL9 7TA, UK.
  • Kingston University, River House, 53-57 High Street, Kingston upon Thames, Surrey, KT1 1LQ, UK.
Dudhia, Jayesh
  • Department of Clinical Sciences and Services, The Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Herts, AL9 7TA, UK.
Smith, Roger K W
  • Department of Clinical Sciences and Services, The Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Herts, AL9 7TA, UK.
Guest, Deborah J
  • Department of Clinical Sciences and Services, The Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Herts, AL9 7TA, UK. djguest@rvc.ac.uk.

MeSH Terms

  • Humans
  • Animals
  • Horses
  • Tumor Necrosis Factor-alpha / metabolism
  • Interleukin-1beta / metabolism
  • NF-kappa B / metabolism
  • Interleukin 1 Receptor Antagonist Protein / genetics
  • Interleukin 1 Receptor Antagonist Protein / metabolism
  • Interferon-gamma / metabolism
  • Tenocytes / metabolism
  • Mesenchymal Stem Cells
  • Tendinopathy / metabolism
  • Cells, Cultured

Grant Funding

  • VET/RS/257 / Horserace Betting Levy Board
  • VET/PRI/782 / Horserace Betting Levy Board
  • S20-921-960 / Petplan Charitable Trust
  • S19-747-786 / Petplan Charitable Trust

Conflict of Interest Statement

The authors declare no competing interests.

References

This article includes 91 references
  1. Abraham AC, Shah SA, Golman M, Song L, Li X, Kurtaliaj I, Akbar M, Millar NL, Abu-Amer Y, Galatz LM, Thomopoulos S. Targeting the NF-κB signaling pathway in chronic tendon disease.. Sci Transl Med 2019 Feb 27;11(481).
    doi: 10.1126/scitranslmed.aav4319pmc: PMC6534967pubmed: 30814338google scholar: lookup
  2. Abraham AC, Shah SA, Thomopoulos S. Targeting Inflammation in Rotator Cuff Tendon Degeneration and Repair.. Tech Shoulder Elb Surg 2017 Sep;18(3):84-90.
    doi: 10.1097/BTE.0000000000000124pmc: PMC5609736pubmed: 28947893google scholar: lookup
  3. Aggarwal S, Pittenger MF. Human mesenchymal stem cells modulate allogeneic immune cell responses.. Blood 2005 Feb 15;105(4):1815-22.
    doi: 10.1182/blood-2004-04-1559pubmed: 15494428google scholar: lookup
  4. Alfredson H, Lorentzon R. Chronic tendon pain: no signs of chemical inflammation but high concentrations of the neurotransmitter glutamate. Implications for treatment?. Curr Drug Targets 2002 Feb;3(1):43-54.
    doi: 10.2174/1389450023348028pubmed: 11899264google scholar: lookup
  5. Barsby T, Bavin EP, Guest DJ. Three-dimensional culture and transforming growth factor beta3 synergistically promote tenogenic differentiation of equine embryo-derived stem cells.. Tissue Eng Part A 2014 Oct;20(19-20):2604-13.
    doi: 10.1089/ten.tea.2013.0457pmc: PMC4195467pubmed: 24628376google scholar: lookup
  6. Barsby T, Guest D. Transforming growth factor beta3 promotes tendon differentiation of equine embryo-derived stem cells.. Tissue Eng Part A 2013 Oct;19(19-20):2156-65.
    doi: 10.1089/ten.tea.2012.0372pubmed: 23611525google scholar: lookup
  7. Bavin EP, Atkinson F, Barsby T, Guest DJ. Scleraxis Is Essential for Tendon Differentiation by Equine Embryonic Stem Cells and in Equine Fetal Tenocytes.. Stem Cells Dev 2017 Mar 15;26(6):441-450.
    doi: 10.1089/scd.2016.0279pubmed: 27899062google scholar: lookup
  8. Becerra P, Valdés Vázquez MA, Dudhia J, Fiske-Jackson AR, Neves F, Hartman NG, Smith RK. Distribution of injected technetium(99m)-labeled mesenchymal stem cells in horses with naturally occurring tendinopathy.. J Orthop Res 2013 Jul;31(7):1096-102.
    doi: 10.1002/jor.22338pubmed: 23508674google scholar: lookup
  9. Bell E, Ivarsson B, Merrill C. Production of a tissue-like structure by contraction of collagen lattices by human fibroblasts of different proliferative potential in vitro.. Proc Natl Acad Sci U S A 1979 Mar;76(3):1274-8.
    doi: 10.1073/pnas.76.3.1274pmc: PMC383233pubmed: 286310google scholar: lookup
  10. Berkoff DJ, Kallianos SA, Eskildsen SM, Weinhold PS. Use of an IL1-receptor antagonist to prevent the progression of tendinopathy in a rat model.. J Orthop Res 2016 Apr;34(4):616-22.
    doi: 10.1002/jor.23057pubmed: 26418607google scholar: lookup
  11. Best KT, Lee FK, Knapp E, Awad HA, Loiselle AE. Deletion of NFKB1 enhances canonical NF-κB signaling and increases macrophage and myofibroblast content during tendon healing.. Sci Rep 2019 Jul 29;9(1):10926.
    doi: 10.1038/s41598-019-47461-5pmc: PMC6662789pubmed: 31358843google scholar: lookup
  12. Bond M, Fabunmi RP, Baker AH, Newby AC. Synergistic upregulation of metalloproteinase-9 by growth factors and inflammatory cytokines: an absolute requirement for transcription factor NF-kappa B.. FEBS Lett 1998 Sep 11;435(1):29-34.
    doi: 10.1016/S0014-5793(98)01034-5pubmed: 9755853google scholar: lookup
  13. Borghaei RC, Rawlings PL Jr, Javadi M, Woloshin J. NF-kappaB binds to a polymorphic repressor element in the MMP-3 promoter.. Biochem Biophys Res Commun 2004 Mar 26;316(1):182-8.
    pubmed: 15003528doi: 10.1016/j.bbrc.2004.02.030google scholar: lookup
  14. Bresnihan B, Alvaro-Gracia JM, Cobby M, Doherty M, Domljan Z, Emery P, Nuki G, Pavelka K, Rau R, Rozman B, Watt I, Williams B, Aitchison R, McCabe D, Musikic P. Treatment of rheumatoid arthritis with recombinant human interleukin-1 receptor antagonist.. Arthritis Rheum 1998 Dec;41(12):2196-204.
    doi: 10.1002/1529-0131(199812)41:12<2196::AID-ART15>3.0.CO;2-2pubmed: 9870876google scholar: lookup
  15. Cassel M, Baur H, Hirschmüller A, Carlsohn A, Fröhlich K, Mayer F. Prevalence of Achilles and patellar tendinopathy and their association to intratendinous changes in adolescent athletes.. Scand J Med Sci Sports 2015 Jun;25(3):e310-8.
    doi: 10.1111/sms.12318pubmed: 25212527google scholar: lookup
  16. Cheshire JL, Baldwin AS Jr. Synergistic activation of NF-kappaB by tumor necrosis factor alpha and gamma interferon via enhanced I kappaB alpha degradation and de novo I kappaBbeta degradation.. Mol Cell Biol 1997 Nov;17(11):6746-54.
    pmc: PMC232529pubmed: 9343439doi: 10.1128/mcb.17.11.6746google scholar: lookup
  17. Dakin SG, Dudhia J, Smith RK. Resolving an inflammatory concept: the importance of inflammation and resolution in tendinopathy.. Vet Immunol Immunopathol 2014 Apr 15;158(3-4):121-7.
    pmc: PMC3991845pubmed: 24556326doi: 10.1016/j.vetimm.2014.01.007google scholar: lookup
  18. Dakin SG, Werling D, Hibbert A, Abayasekara DR, Young NJ, Smith RK, Dudhia J. Macrophage sub-populations and the lipoxin A4 receptor implicate active inflammation during equine tendon repair.. PLoS One 2012;7(2):e32333.
    doi: 10.1371/journal.pone.0032333pmc: PMC3284560pubmed: 22384219google scholar: lookup
  19. de Witte SF, Franquesa M, Baan CC, Hoogduijn MJ. Toward Development of iMesenchymal Stem Cells for Immunomodulatory Therapy.. Front Immunol 2015;6:648.
    doi: 10.3389/fimmu.2015.00648pmc: PMC4701910pubmed: 26779185google scholar: lookup
  20. Deb A, Haque SJ, Mogensen T, Silverman RH, Williams BR. RNA-dependent protein kinase PKR is required for activation of NF-kappa B by IFN-gamma in a STAT1-independent pathway.. J Immunol 2001 May 15;166(10):6170-80.
    doi: 10.4049/jimmunol.166.10.6170pubmed: 11342638google scholar: lookup
  21. Dragoljevic D, Lee MKS, Louis C, Shihata W, Kraakman MJ, Hansen J, Masters SL, Hanaoka BY, Nagareddy PR, Lancaster GI, Wicks IP, Murphy AJ. Inhibition of interleukin-1β signalling promotes atherosclerotic lesion remodelling in mice with inflammatory arthritis.. Clin Transl Immunology 2020;9(11):e1206.
    doi: 10.1002/cti2.1206pmc: PMC7652637pubmed: 33204425google scholar: lookup
  22. Durbin JE, Hackenmiller R, Simon MC, Levy DE. Targeted disruption of the mouse Stat1 gene results in compromised innate immunity to viral disease.. Cell 1996 Feb 9;84(3):443-50.
    doi: 10.1016/S0092-8674(00)81289-1pubmed: 8608598google scholar: lookup
  23. Dyson SJ. Medical management of superficial digital flexor tendonitis: a comparative study in 219 horses (1992-2000).. Equine Vet J 2004 Jul;36(5):415-9.
    doi: 10.2746/0425164044868422pubmed: 15253082google scholar: lookup
  24. Ellis I, Schnabel LV, Berglund AK. Defining the Profile: Characterizing Cytokines in Tendon Injury to Improve Clinical Therapy.. J Immunol Regen Med 2022 May;16.
    doi: 10.1016/j.regen.2022.100059pmc: PMC8932644pubmed: 35309714google scholar: lookup
  25. Fedorka CE, El-Sheikh Ali H, Scoggin KE, Loux SC, Ball BA, Troedsson MHT. Tumor necrosis factor signaling during equine placental infection leads to pro-apoptotic and necroptotic outcomes.. J Reprod Immunol 2022 Aug;152:103655.
    doi: 10.1016/j.jri.2022.103655pubmed: 35716439google scholar: lookup
  26. Filardo G, Di Matteo B, Kon E, Merli G, Marcacci M. Platelet-rich plasma in tendon-related disorders: results and indications.. Knee Surg Sports Traumatol Arthrosc 2018 Jul;26(7):1984-1999.
    doi: 10.1007/s00167-016-4261-4pubmed: 27665095google scholar: lookup
  27. Fredberg U, Ostgaard R. Effect of ultrasound-guided, peritendinous injections of adalimumab and anakinra in chronic Achilles tendinopathy: a pilot study.. Scand J Med Sci Sports 2009 Jun;19(3):338-44.
    doi: 10.1111/j.1600-0838.2008.00813.xpubmed: 18492052google scholar: lookup
  28. Freedman BR, Adu-Berchie K, Barnum C, Fryhofer GW, Salka NS, Shetye S, Soslowsky LJ. Nonsurgical treatment reduces tendon inflammation and elevates tendon markers in early healing.. J Orthop Res 2022 Oct;40(10):2308-2319.
    doi: 10.1002/jor.25251pmc: PMC9209559pubmed: 34935170google scholar: lookup
  29. Gardner AK, Kelly CS, van Eps AW, Burns TA, Watts MR, Belknap JK. Mitogen-activated kinase pathway activation in epidermal lamellae in the acute stages of carbohydrate overload laminitis models and the effect of regional deep hypothermia on signalling pathways.. Equine Vet J 2016 Sep;48(5):633-40.
    doi: 10.1111/evj.12488pubmed: 26222495google scholar: lookup
  30. Gaspar D, Spanoudes K, Holladay C, Pandit A, Zeugolis D. Progress in cell-based therapies for tendon repair.. Adv Drug Deliv Rev 2015 Apr;84:240-56.
    doi: 10.1016/j.addr.2014.11.023pubmed: 25543005google scholar: lookup
  31. Geburek F, Lietzau M, Beineke A, Rohn K, Stadler PM. Effect of a single injection of autologous conditioned serum (ACS) on tendon healing in equine naturally occurring tendinopathies.. Stem Cell Res Ther 2015 Jun 26;6(1):126.
    doi: 10.1186/s13287-015-0115-0pmc: PMC4513386pubmed: 26113022google scholar: lookup
  32. Gehwolf R, Schwemberger B, Jessen M, Korntner S, Wagner A, Lehner C, Weissenbacher N, Tempfer H, Traweger A. Global Responses of Il-1β-Primed 3D Tendon Constructs to Treatment with Pulsed Electromagnetic Fields.. Cells 2019 Apr 30;8(5).
    doi: 10.3390/cells8050399pmc: PMC6562657pubmed: 31052237google scholar: lookup
  33. Godwin EE, Young NJ, Dudhia J, Beamish IC, Smith RK. Implantation of bone marrow-derived mesenchymal stem cells demonstrates improved outcome in horses with overstrain injury of the superficial digital flexor tendon.. Equine Vet J 2012 Jan;44(1):25-32.
    doi: 10.1111/j.2042-3306.2011.00363.xpubmed: 21615465google scholar: lookup
  34. Gomiero C, Bertolutti G, Martinello T, Van Bruaene N, Broeckx SY, Patruno M, Spaas JH. Tenogenic induction of equine mesenchymal stem cells by means of growth factors and low-level laser technology.. Vet Res Commun 2016 Mar;40(1):39-48.
    doi: 10.1007/s11259-016-9652-ypubmed: 26757735google scholar: lookup
  35. Gough DJ, Levy DE, Johnstone RW, Clarke CJ. IFNgamma signaling-does it mean JAK-STAT?. Cytokine Growth Factor Rev 2008 Oct-Dec;19(5-6):383-94.
    doi: 10.1016/j.cytogfr.2008.08.004pubmed: 18929502google scholar: lookup
  36. Grinnell F, Petroll WM. Cell motility and mechanics in three-dimensional collagen matrices.. Annu Rev Cell Dev Biol 2010;26:335-61.
    doi: 10.1146/annurev.cellbio.042308.113318pubmed: 19575667google scholar: lookup
  37. Guest DJ, Dudhia J, Smith RKW, Roberts SJ, Conzemius M, Innes JF, Fortier LA, Meeson RL. Position Statement: Minimal Criteria for Reporting Veterinary and Animal Medicine Research for Mesenchymal Stromal/Stem Cells in Orthopedic Applications.. Front Vet Sci 2022;9:817041.
    pmc: PMC8936138pubmed: 35321059doi: 10.3389/fvets.2022.817041google scholar: lookup
  38. Guest DJ, Smith MR, Allen WR. Equine embryonic stem-like cells and mesenchymal stromal cells have different survival rates and migration patterns following their injection into damaged superficial digital flexor tendon.. Equine Vet J 2010 Oct;42(7):636-42.
    pubmed: 20840579doi: 10.1111/j.2042-3306.2010.00112.xgoogle scholar: lookup
  39. Guest DJ, Ousey JC, Smith MR. Defining the expression of marker genes in equine mesenchymal stromal cells.. Stem Cells Cloning 2008;1:1-9.
    pmc: PMC3781685pubmed: 24198500doi: 10.2147/sccaa.s3824google scholar: lookup
  40. Gupta SC, Sundaram C, Reuter S, Aggarwal BB. Inhibiting NF-κB activation by small molecules as a therapeutic strategy.. Biochim Biophys Acta 2010 Oct-Dec;1799(10-12):775-87.
    pmc: PMC2955987pubmed: 20493977doi: 10.1016/j.bbagrm.2010.05.004google scholar: lookup
  41. Hallegua DS, Weisman MH. Potential therapeutic uses of interleukin 1 receptor antagonists in human diseases.. Ann Rheum Dis 2002 Nov;61(11):960-7.
    doi: 10.1136/ard.61.11.960pmc: PMC1753951pubmed: 12379516google scholar: lookup
  42. Hiroi M, Ohmori Y. Transcriptional synergism between NF-κB and STAT1. J Oral Biosci 2005;47:230–242.
  43. Hosaka Y, Kirisawa R, Yamamoto E, Ueda H, Iwai H, Takehana K. Localization of cytokines in tendinocytes of the superficial digital flexor tendon in the horse.. J Vet Med Sci 2002 Oct;64(10):945-7.
    doi: 10.1292/jvms.64.945pubmed: 12419874google scholar: lookup
  44. Jo CH, Lim HJ, Yoon KS. Characterization of Tendon-Specific Markers in Various Human Tissues, Tenocytes and Mesenchymal Stem Cells.. Tissue Eng Regen Med 2019 Apr;16(2):151-159.
    doi: 10.1007/s13770-019-00182-2pmc: PMC6439073pubmed: 30989042google scholar: lookup
  45. John T, Lodka D, Kohl B, Ertel W, Jammrath J, Conrad C, Stoll C, Busch C, Schulze-Tanzil G. Effect of pro-inflammatory and immunoregulatory cytokines on human tenocytes.. J Orthop Res 2010 Aug;28(8):1071-7.
    pubmed: 20127972doi: 10.1002/jor.21079google scholar: lookup
  46. Jones GC, Corps AN, Pennington CJ, Clark IM, Edwards DR, Bradley MM, Hazleman BL, Riley GP. Expression profiling of metalloproteinases and tissue inhibitors of metalloproteinases in normal and degenerate human achilles tendon.. Arthritis Rheum 2006 Mar;54(3):832-42.
    doi: 10.1002/art.21672pubmed: 16508964google scholar: lookup
  47. Jové M, Planavila A, Laguna JC, Vázquez-Carrera M. Palmitate-induced interleukin 6 production is mediated by protein kinase C and nuclear-factor kappaB activation and leads to glucose transporter 4 down-regulation in skeletal muscle cells.. Endocrinology 2005 Jul;146(7):3087-95.
    doi: 10.1210/en.2004-1560pubmed: 15802498google scholar: lookup
  48. Kim J, Hematti P. Mesenchymal stem cell-educated macrophages: a novel type of alternatively activated macrophages.. Exp Hematol 2009 Dec;37(12):1445-53.
    doi: 10.1016/j.exphem.2009.09.004pmc: PMC2783735pubmed: 19772890google scholar: lookup
  49. Krampera M, Cosmi L, Angeli R, Pasini A, Liotta F, Andreini A, Santarlasci V, Mazzinghi B, Pizzolo G, Vinante F, Romagnani P, Maggi E, Romagnani S, Annunziato F. Role for interferon-gamma in the immunomodulatory activity of human bone marrow mesenchymal stem cells.. Stem Cells 2006 Feb;24(2):386-98.
    doi: 10.1634/stemcells.2005-0008pubmed: 16123384google scholar: lookup
  50. Lee CW, Lin CC, Lin WN, Liang KC, Luo SF, Wu CB, Wang SW, Yang CM. TNF-alpha induces MMP-9 expression via activation of Src/EGFR, PDGFR/PI3K/Akt cascade and promotion of NF-kappaB/p300 binding in human tracheal smooth muscle cells.. Am J Physiol Lung Cell Mol Physiol 2007 Mar;292(3):L799-812.
    doi: 10.1152/ajplung.00311.2006pubmed: 17158602google scholar: lookup
  51. Legendre F, Bogdanowicz P, Boumediene K, Pujol JP. Role of interleukin 6 (IL-6)/IL-6R-induced signal tranducers and activators of transcription and mitogen-activated protein kinase/extracellular.. J Rheumatol 2005 Jul;32(7):1307-16.
    pubmed: 15996070
  52. Liao X, Falcon ND, Mohammed AA, Paterson YZ, Mayes AG, Guest DJ, Saeed A. Synthesis and Formulation of Four-Arm PolyDMAEA-siRNA Polyplex for Transient Downregulation of Collagen Type III Gene Expression in TGF-β1 Stimulated Tenocyte Culture.. ACS Omega 2020 Jan 28;5(3):1496-1505.
    doi: 10.1021/acsomega.9b03216pmc: PMC6990625pubmed: 32010823google scholar: lookup
  53. Lieberman LA, Banica M, Reiner SL, Hunter CA. STAT1 plays a critical role in the regulation of antimicrobial effector mechanisms, but not in the development of Th1-type responses during toxoplasmosis.. J Immunol 2004 Jan 1;172(1):457-63.
    doi: 10.4049/jimmunol.172.1.457pubmed: 14688355google scholar: lookup
  54. Lin TW, Cardenas L, Glaser DL, Soslowsky LJ. Tendon healing in interleukin-4 and interleukin-6 knockout mice.. J Biomech 2006;39(1):61-9.
    doi: 10.1016/j.jbiomech.2004.11.009pubmed: 16271588google scholar: lookup
  55. Liu T, Zhang L, Joo D, Sun SC. NF-κB signaling in inflammation.. Signal Transduct Target Ther 2017;2:17023-.
    doi: 10.1038/sigtrans.2017.23pmc: PMC5661633pubmed: 29158945google scholar: lookup
  56. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.. Methods 2001 Dec;25(4):402-8.
    doi: 10.1006/meth.2001.1262pubmed: 11846609google scholar: lookup
  57. Manning CN, Martel C, Sakiyama-Elbert SE, Silva MJ, Shah S, Gelberman RH, Thomopoulos S. Adipose-derived mesenchymal stromal cells modulate tendon fibroblast responses to macrophage-induced inflammation in vitro.. Stem Cell Res Ther 2015 Apr 16;6(1):74.
    doi: 10.1186/s13287-015-0059-4pmc: PMC4416344pubmed: 25889287google scholar: lookup
  58. Marsolais D, Côté CH, Frenette J. Nonsteroidal anti-inflammatory drug reduces neutrophil and macrophage accumulation but does not improve tendon regeneration.. Lab Invest 2003 Jul;83(7):991-9.
    doi: 10.1097/01.LAB.0000078688.07696.ACpubmed: 12861039google scholar: lookup
  59. Martincuks A, Andryka K, Küster A, Schmitz-Van de Leur H, Komorowski M, Müller-Newen G. Nuclear translocation of STAT3 and NF-κB are independent of each other but NF-κB supports expression and activation of STAT3.. Cell Signal 2017 Apr;32:36-47.
    doi: 10.1016/j.cellsig.2017.01.006pubmed: 28089769google scholar: lookup
  60. McClellan A, Evans R, Sze C, Kan S, Paterson Y, Guest D. A novel mechanism for the protection of embryonic stem cell derived tenocytes from inflammatory cytokine interleukin 1 beta.. Sci Rep 2019 Feb 26;9(1):2755.
    doi: 10.1038/s41598-019-39370-4pmc: PMC6391488pubmed: 30808942google scholar: lookup
  61. McClellan A, Paterson YZ, Paillot R, Guest DJ. Equine Fetal, Adult, and Embryonic Stem Cell-Derived Tenocytes Are All Immune Privileged but Exhibit Different Immune Suppressive Properties In Vitro.. Stem Cells Dev 2019 Nov 1;28(21):1413-1423.
    doi: 10.1089/scd.2019.0120pubmed: 31507234google scholar: lookup
  62. Millar NL, Akbar M, Campbell AL, Reilly JH, Kerr SC, McLean M, Frleta-Gilchrist M, Fazzi UG, Leach WJ, Rooney BP, Crowe LA, Murrell GA, McInnes IB. IL-17A mediates inflammatory and tissue remodelling events in early human tendinopathy.. Sci Rep 2016 Jun 6;6:27149.
    doi: 10.1038/srep27149pmc: PMC4893609pubmed: 27263531google scholar: lookup
  63. Millar NL, Murrell GA, McInnes IB. Inflammatory mechanisms in tendinopathy - towards translation.. Nat Rev Rheumatol 2017 Jan 25;13(2):110-122.
    doi: 10.1038/nrrheum.2016.213pubmed: 28119539google scholar: lookup
  64. Morita W, Dakin SG, Snelling SJB, Carr AJ. Cytokines in tendon disease: A Systematic Review.. Bone Joint Res 2017 Dec;6(12):656-664.
    doi: 10.1302/2046-3758.612.BJR-2017-0112.R1pmc: PMC5935810pubmed: 29203638google scholar: lookup
  65. Noronha NC, Mizukami A, Caliári-Oliveira C, Cominal JG, Rocha JLM, Covas DT, Swiech K, Malmegrim KCR. Priming approaches to improve the efficacy of mesenchymal stromal cell-based therapies.. Stem Cell Res Ther 2019 May 2;10(1):131.
    doi: 10.1186/s13287-019-1259-0pmc: PMC6498654pubmed: 31046833google scholar: lookup
  66. Novotny NM, Markel TA, Crisostomo PR, Meldrum DR. Differential IL-6 and VEGF secretion in adult and neonatal mesenchymal stem cells: role of NFkB.. Cytokine 2008 Aug;43(2):215-9.
    doi: 10.1016/j.cyto.2008.05.015pubmed: 18621544google scholar: lookup
  67. Paterson YZ, Cribbs A, Espenel M, Smith EJ, Henson FMD, Guest DJ. Genome-wide transcriptome analysis reveals equine embryonic stem cell-derived tenocytes resemble fetal, not adult tenocytes.. Stem Cell Res Ther 2020 May 19;11(1):184.
    doi: 10.1186/s13287-020-01692-wpmc: PMC7238619pubmed: 32430075google scholar: lookup
  68. Paterson YZ, Rash N, Garvican ER, Paillot R, Guest DJ. Equine mesenchymal stromal cells and embryo-derived stem cells are immune privileged in vitro.. Stem Cell Res Ther 2014 Jul 30;5(4):90.
    doi: 10.1186/scrt479pmc: PMC4247727pubmed: 25080326google scholar: lookup
  69. Patterson-Kane JC, Becker DL, Rich T. The pathogenesis of tendon microdamage in athletes: the horse as a natural model for basic cellular research.. J Comp Pathol 2012 Aug-Oct;147(2-3):227-47.
    doi: 10.1016/j.jcpa.2012.05.010pubmed: 22789861google scholar: lookup
  70. Rees JD, Stride M, Scott A. Tendons--time to revisit inflammation.. Br J Sports Med 2014 Nov;48(21):1553-7.
    doi: 10.1136/bjsports-2012-091957pmc: PMC4215290pubmed: 23476034google scholar: lookup
  71. Robertson CM, Chen CT, Shindle MK, Cordasco FA, Rodeo SA, Warren RF. Failed healing of rotator cuff repair correlates with altered collagenase and gelatinase in supraspinatus and subscapularis tendons.. Am J Sports Med 2012 Sep;40(9):1993-2001.
    doi: 10.1177/0363546512456519pubmed: 22896627google scholar: lookup
  72. Schwartz AJ, Sarver DC, Sugg KB, Dzierzawski JT, Gumucio JP, Mendias CL. p38 MAPK signaling in postnatal tendon growth and remodeling.. PLoS One 2015;10(3):e0120044.
    doi: 10.1371/journal.pone.0120044pmc: PMC4359143pubmed: 25768932google scholar: lookup
  73. Smith RK, Werling NJ, Dakin SG, Alam R, Goodship AE, Dudhia J. Beneficial effects of autologous bone marrow-derived mesenchymal stem cells in naturally occurring tendinopathy.. PLoS One 2013;8(9):e75697.
    doi: 10.1371/journal.pone.0075697pmc: PMC3783421pubmed: 24086616google scholar: lookup
  74. Sobhani S, Dekker R, Postema K, Dijkstra PU. Epidemiology of ankle and foot overuse injuries in sports: A systematic review.. Scand J Med Sci Sports 2013 Dec;23(6):669-86.
    doi: 10.1111/j.1600-0838.2012.01509.xpubmed: 22846101google scholar: lookup
  75. Spaas JH, De Schauwer C, Cornillie P, Meyer E, Van Soom A, Van de Walle GR. Culture and characterisation of equine peripheral blood mesenchymal stromal cells.. Vet J 2013 Jan;195(1):107-13.
    doi: 10.1016/j.tvjl.2012.05.006pubmed: 22717781google scholar: lookup
  76. Stolk M, Klatte-Schulz F, Schmock A, Minkwitz S, Wildemann B, Seifert M. New insights into tenocyte-immune cell interplay in an in vitro model of inflammation.. Sci Rep 2017 Aug 29;7(1):9801.
    doi: 10.1038/s41598-017-09875-xpmc: PMC5575127pubmed: 28851983google scholar: lookup
  77. Sullivan CB, Porter RM, Evans CH, Ritter T, Shaw G, Barry F, Murphy JM. TNFα and IL-1β influence the differentiation and migration of murine MSCs independently of the NF-κB pathway.. Stem Cell Res Ther 2014 Aug 27;5(4):104.
    doi: 10.1186/scrt492pmc: PMC4177434pubmed: 25163844google scholar: lookup
  78. Tang JB, Wu YF, Cao Y, Chen CH, Zhou YL, Avanessian B, Shimada M, Wang XT, Liu PY. Basic FGF or VEGF gene therapy corrects insufficiency in the intrinsic healing capacity of tendons.. Sci Rep 2016 Feb 11;6:20643.
    doi: 10.1038/srep20643pmc: PMC4749961pubmed: 26865366google scholar: lookup
  79. Tarafder S, Chen E, Jun Y, Kao K, Sim KH, Back J, Lee FY, Lee CH. Tendon stem/progenitor cells regulate inflammation in tendon healing via JNK and STAT3 signaling.. FASEB J 2017 Sep;31(9):3991-3998.
    doi: 10.1096/fj.201700071Rpmc: PMC5572690pubmed: 28533328google scholar: lookup
  80. Tsai CL, Chen WC, Hsieh HL, Chi PL, Hsiao LD, Yang CM. TNF-α induces matrix metalloproteinase-9-dependent soluble intercellular adhesion molecule-1 release via TRAF2-mediated MAPKs and NF-κB activation in osteoblast-like MC3T3-E1 cells.. J Biomed Sci 2014 Feb 5;21(1):12.
    doi: 10.1186/1423-0127-21-12pmc: PMC3926355pubmed: 24502696google scholar: lookup
  81. Tsuzaki M, Guyton G, Garrett W, Archambault JM, Herzog W, Almekinders L, Bynum D, Yang X, Banes AJ. IL-1 beta induces COX2, MMP-1, -3 and -13, ADAMTS-4, IL-1 beta and IL-6 in human tendon cells.. J Orthop Res 2003 Mar;21(2):256-64.
    doi: 10.1016/S0736-0266(02)00141-9pubmed: 12568957google scholar: lookup
  82. van Buul GM, Villafuertes E, Bos PK, Waarsing JH, Kops N, Narcisi R, Weinans H, Verhaar JA, Bernsen MR, van Osch GJ. Mesenchymal stem cells secrete factors that inhibit inflammatory processes in short-term osteoarthritic synovium and cartilage explant culture.. Osteoarthritis Cartilage 2012 Oct;20(10):1186-96.
    doi: 10.1016/j.joca.2012.06.003pubmed: 22771777google scholar: lookup
  83. Viganò M, Lugano G, Perucca Orfei C, Menon A, Ragni E, Colombini A, De Luca P, Randelli P, de Girolamo L. Autologous Microfragmented Adipose Tissue Reduces the Catabolic and Fibrosis Response in an In Vitro Model of Tendon Cell Inflammation.. Stem Cells Int 2019;2019:5620286.
    doi: 10.1155/2019/5620286pmc: PMC6915130pubmed: 31885616google scholar: lookup
  84. Vincenti MP, Coon CI, Brinckerhoff CE. Nuclear factor kappaB/p50 activates an element in the distal matrix metalloproteinase 1 promoter in interleukin-1beta-stimulated synovial fibroblasts.. Arthritis Rheum 1998 Nov;41(11):1987-94.
    doi: 10.1002/1529-0131(199811)41:11<1987::AID-ART14>3.0.CO;2-8pubmed: 9811054google scholar: lookup
  85. Vinhas A, Rodrigues MT, Gonçalves AI, Reis RL, Gomes ME. Magnetic responsive materials modulate the inflammatory profile of IL-1β conditioned tendon cells.. Acta Biomater 2020 Nov;117:235-245.
    doi: 10.1016/j.actbio.2020.09.028pubmed: 32966921google scholar: lookup
  86. Wang Y, He G, Tang H, Shi Y, Kang X, Lyu J, Zhu M, Zhou M, Yang M, Mu M, Chen W, Zhou B, Zhang J, Tang K. Aspirin inhibits inflammation and scar formation in the injury tendon healing through regulating JNK/STAT-3 signalling pathway.. Cell Prolif 2019 Jul;52(4):e12650.
    doi: 10.1111/cpr.12650pmc: PMC6668964pubmed: 31225686google scholar: lookup
  87. Williams RB, Harkins LS, Hammond CJ, Wood JL. Racehorse injuries, clinical problems and fatalities recorded on British racecourses from flat racing and National Hunt racing during 1996, 1997 and 1998.. Equine Vet J 2001 Sep;33(5):478-86.
    doi: 10.2746/042516401776254808pubmed: 11558743google scholar: lookup
  88. Xie F, Xiao P, Chen D, Xu L, Zhang B. miRDeepFinder: a miRNA analysis tool for deep sequencing of plant small RNAs.. Plant Mol Biol 2012 Jan 31;.
    doi: 10.1007/s11103-012-9885-2pubmed: 22290409google scholar: lookup
  89. Yang S, Yu M, Sun L, Xiao W, Yang X, Sun L, Zhang C, Ma Y, Yang H, Liu Y, Lu D, Teitelbaum DH, Yang H. Interferon-γ-induced intestinal epithelial barrier dysfunction by NF-κB/HIF-1α pathway.. J Interferon Cytokine Res 2014 Mar;34(3):195-203.
    doi: 10.1089/jir.2013.0044pubmed: 24237301google scholar: lookup
  90. Yang TH, Thoreson AR, Gingery A, Larson DR, Passe SM, An KN, Zhao C, Amadio PC. Collagen gel contraction as a measure of fibroblast function in an animal model of subsynovial connective tissue fibrosis.. J Orthop Res 2015 May;33(5):668-74.
    doi: 10.1002/jor.22835pmc: PMC4415498pubmed: 25626430google scholar: lookup
  91. Zhang Y, Ge XH, Guo XJ, Guan SB, Li XM, Gu W, Xu WG. Bone Marrow Mesenchymal Stem Cells Inhibit the Function of Dendritic Cells by Secreting Galectin-1.. Biomed Res Int 2017;2017:3248605.
    doi: 10.1155/2017/3248605pmc: PMC5497648pubmed: 28713822google scholar: lookup

Citations

This article has been cited 0 times.
Subscribe to our newsletter
Join 99,344 horse owners like you who receive our email updates on horse health and nutrition.