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Dietary extra-virgin olive oil prevents inflammatory response and cartilage matrix degradation in murine collagen-induced arthritis

Abstract

Purpose

Current experimental studies support a beneficial role of extra-virgin olive oil (EVOO) in several inflammatory diseases. The present study was designed to evaluate the effects of dietary EVOO on type II collagen-induced arthritis (CIA) in mice.

Methods

DBA-1/J mice were randomized in four experimental groups (10 or 15 animals per group): (1) Sham sunflower diet (SO-Sham), (2) CIA sunflower diet (SO-CIA), (3) Sham EVOO diet (EVOO-Sham) and (4) CIA EVOO diet (EVOO–CIA) group. After 6 weeks, arthritis was induced by type II collagen. Mice were sacrified 42 days after first immunization. In addition to macroscopic and histological analyses, serum levels of cartilage olimeric matrix protein (COMP), metalloproteinase-3 (MMP-3) and pro-inflammatory cytokines levels were evaluated by ELISA. The expressions of heme oxygenase-1 (HO-1), nuclear factor E2-related factor 2 (Nrf2), mitogen-activated protein kinases (MAPKs), Janus kinase-signal transducer and activator of transcription (JAK/STAT) and nuclear transcription factor-kappa B (NF-κB) pathways were studied by western blotting.

Results

EVOO diet significantly reduced joint edema and cartilage destruction, preventing the arthritis development. Dietary EVOO significantly decreased serum COMP and MMP-3 levels, as well as, the pro-inflammatory cytokines levels (TNF-α, IL-1β and IL-17). Moreover, the activation of JAK/STAT, MAPKs and NF-κB pathways was drastically ameliorated. According to Nrf2 and HO-1, the protein expressions were up-regulated in those mice fed with EVOO.

Conclusion

These results support the interest of EVOO as a beneficial functional food to prevent the development of the rheumatoid arthritis (RA).

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References

  1. Li F, Guo N, Ma Y, Ning B, Wang Y, Kou L (2014) Inhibition of P2X4 suppresses joint inflammation and damage in collagen-induced arthritis. Inflammation 37(1):146–153. doi:10.1007/s10753-013-9723-y

    Article  CAS  Google Scholar 

  2. Moon SJ, Park JS, Woo YJ, Lim MA, Kim SM, Lee SY, Kim EK, Lee HJ, Lee WS, Park SH, Jeong JH, Park SH, Kim HY, Cho ML, Min JK (2014) Rebamipide suppresses collagen-induced arthritis through reciprocal regulation of th17/treg cell differentiation and heme oxygenase 1 induction. Arthritis Rheumatol 66(4):874–885. doi:10.1002/art.38310

    Article  CAS  Google Scholar 

  3. Noack M, Miossec P (2014) Th17 and regulatory T cell balance in autoimmune and inflammatory diseases. Autoimmun Rev 13(6):668–677. doi:10.1016/j.autrev.2013.12.004

    Article  CAS  Google Scholar 

  4. Azizi G, Jadidi-Niaragh F, Mirshafiey A (2013) Th17 Cells in Immunopathogenesis and treatment of rheumatoid arthritis. Int J Rheum Dis 16(3):243–253. doi:10.1111/1756-185X.12132

    Article  CAS  Google Scholar 

  5. Li Y, Wang S, Wang Y, Zhou C, Chen G, Shen W, Li C, Lin W, Lin S, Huang H, Liu P, Shen X (2013) Inhibitory effect of the antimalarial agent artesunate on collagen-induced arthritis in rats through nuclear factor kappa B and mitogen-activated protein kinase signaling pathway. Transl Res 161(2):89–98. doi:10.1016/j.trsl.2012.06.001

    Article  CAS  Google Scholar 

  6. Criado G, Risco A, Alsina-Beauchamp D, Perez-Lorenzo MJ, Escos A, Cuenda A (2014) Alternative p38 MAPKs are essential for collagen-induced arthritis. Arthritis Rheumatol 66(5):1208–1217. doi:10.1002/art.38327

    Article  CAS  Google Scholar 

  7. Peck A, Mellins ED (2009) Breaking old paradigms: th17 cells in autoimmune arthritis. Clin Immunol 132(3):295–304. doi:10.1016/j.clim.2009.03.522

    Article  CAS  Google Scholar 

  8. Aaronson DS, Horvath CM (2002) A road map for those who don’t know JAK-STAT. Science 296(5573):1653–1655. doi:10.1126/science.1071545

    Article  CAS  Google Scholar 

  9. Morel J, Berenbaum F (2004) Signal transduction pathways: new targets for treating rheumatoid arthritis. Joint Bone Spine 71(6):503–510. doi:10.1016/j.jbspin.2004.03.004

    Article  Google Scholar 

  10. Ferrandiz ML, Maicas N, Garcia-Arnandis I, Terencio MC, Motterlini R, Devesa I, Joosten LA, van den Berg WB, Alcaraz MJ (2008) Treatment with a CO-releasing molecule (CORM-3) reduces joint inflammation and erosion in murine collagen-induced arthritis. Ann Rheum Dis 67(9):1211–1217. doi:10.1136/ard.2007.082412

    Article  CAS  Google Scholar 

  11. Jung KH, Hong SW, Zheng HM, Lee HS, Lee H, Lee DH, Lee SY, Hong SS (2010) Melatonin ameliorates cerulein-induced pancreatitis by the modulation of nuclear erythroid 2-related factor 2 and nuclear factor-kappaB in rats. J Pineal Res 48(3):239–250. doi:10.1111/j.1600-079X.2010.00748.x

    Article  CAS  Google Scholar 

  12. Cardeno A, Sanchez-Hidalgo M, Alarcon-de-la-Lastra C (2013) An up-date of olive oil phenols in inflammation and cancer: molecular mechanisms and clinical implications. Curr Med Chem 20(37):4758–4776

    Article  CAS  Google Scholar 

  13. Berbert AA, Kondo CR, Almendra CL, Matsuo T, Dichi I (2005) Supplementation of fish oil and olive oil in patients with rheumatoid arthritis. Nutrition 21(2):131–136. doi:10.1016/j.nut.2004.03.023

    Article  CAS  Google Scholar 

  14. de la Lastra Romero CA (2011) An up-date of olive oil and bioactive constituents in health: molecular mechanisms and clinical implications. Curr Pharm Des 17(8):752–753

    Article  Google Scholar 

  15. Impellizzeri D, Esposito E, Mazzon E, Paterniti I, Di Paola R, Morittu VM, Procopio A, Britti D, Cuzzocrea S (2011) Oleuropein aglycone, an olive oil compound, ameliorates development of arthritis caused by injection of collagen type II in mice. J Pharmacol Exp Ther 339(3):859–869. doi:10.1124/jpet.111.182808

    Article  CAS  Google Scholar 

  16. Impellizzeri D, Esposito E, Mazzon E, Paterniti I, Di Paola R, Bramanti P, Morittu VM, Procopio A, Perri E, Britti D, Cuzzocrea S (2012) The effects of a polyphenol present in olive oil, oleuropein aglycone, in an experimental model of spinal cord injury in mice. Biochem Pharmacol 83(10):1413–1426. doi:10.1016/j.bcp.2012.02.001

    Article  CAS  Google Scholar 

  17. Gong D, Geng C, Jiang L, Cao J, Yoshimura H, Zhong L (2009) Effects of hydroxytyrosol-20 on carrageenan-induced acute inflammation and hyperalgesia in rats. Phytother Res PTR 23(5):646–650. doi:10.1002/ptr.2686

    Article  CAS  Google Scholar 

  18. Martinez-Dominguez E, de la Puerta R, Ruiz-Gutierrez V (2001) Protective effects upon experimental inflammation models of a polyphenol-supplemented virgin olive oil diet. Inflamm Res 50(2):102–106

    Article  CAS  Google Scholar 

  19. Sanchez-Fidalgo S, Sanchez de Ibarguen L, Cardeno A, Alarcon de la Lastra C (2012) Influence of extra virgin olive oil diet enriched with hydroxytyrosol in a chronic DSS colitis model. Eur J Nutr 51(4):497–506. doi:10.1007/s00394-011-0235-y

    Article  CAS  Google Scholar 

  20. Sanchez-Fidalgo S, Cardeno A, Sanchez-Hidalgo M, Aparicio-Soto M, de la Lastra CA (2013) Dietary extra virgin olive oil polyphenols supplementation modulates DSS-induced chronic colitis in mice. J Nutr Biochem 24(7):1401–1413. doi:10.1016/j.jnutbio.2012.11.008

    Article  CAS  Google Scholar 

  21. Sanchez-Fidalgo S, Cardeno A, Sanchez-Hidalgo M, Aparicio-Soto M, Villegas I, Rosillo MA, de la Lastra CA (2012) Dietary unsaponifiable fraction from extra virgin olive oil supplementation attenuates acute ulcerative colitis in mice. Eur J Pharm Sci 48(3):572–581. doi:10.1016/j.ejps.2012.12.004

    Article  Google Scholar 

  22. Sanchez-Fidalgo S, Villegas I, Cardeno A, Talero E, Sanchez-Hidalgo M, Motilva V, Alarcon de la Lastra C (2010) Extra-virgin olive oil-enriched diet modulates DSS-colitis-associated colon carcinogenesis in mice. Clin Nutr 29(5):663–673. doi:10.1016/j.clnu.2010.03.003

    Article  CAS  Google Scholar 

  23. Musumeci G, Trovato FM, Pichler K, Weinberg AM, Loreto C, Castrogiovanni P (2013) Extra-virgin olive oil diet and mild physical activity prevent cartilage degeneration in an osteoarthritis model: an in vivo and in vitro study on lubricin expression. J Nutr Biochem 24(12):2064–2075

    Article  CAS  Google Scholar 

  24. Loued S, Berrougui H, Componova P, Ikhlef S, Helal O, Khalil A (2013) Extra-virgin olive oil consumption reduces the age-related decrease in HDL and paraoxonase 1 anti-inflammatory activities. Br J Nutr 110(7):1272–1284. doi:10.1017/S0007114513000482

    Article  CAS  Google Scholar 

  25. Rosillo MA, Sanchez-Hidalgo M, Cardeno A, de la Lastra CA (2011) Protective effect of ellagic acid, a natural polyphenolic compound, in a murine model of Crohn’s disease. Biochem Pharmacol 82(7):737–745. doi:10.1016/j.bcp.2011.06.043

    Article  CAS  Google Scholar 

  26. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254

    Article  CAS  Google Scholar 

  27. McInnes IB, Schett G (2011) The pathogenesis of rheumatoid arthritis. N Engl J Med 365(23):2205–2219. doi:10.7748/phc2011.11.21.9.29.c8797

    Article  CAS  Google Scholar 

  28. Park JS, Lim MA, Cho ML, Ryu JG, Moon YM, Jhun JY, Byun JK, Kim EK, Hwang SY, Ju JH, Kwok SK, Kim HY (2013) p53 controls autoimmune arthritis via STAT-mediated regulation of the Th17 cell/Treg cell balance in mice. Arthritis Rheum 65(4):949–959. doi:10.1002/art.37841

    Article  CAS  Google Scholar 

  29. Schurgers E, Billiau A, Matthys P (2011) Collagen-induced arthritis as an animal model for rheumatoid arthritis: focus on interferon-gamma. J Interferon Cytokine Res 31(12):917–926. doi:10.1089/jir.2011.0056

    Article  CAS  Google Scholar 

  30. Komatsu N, Takayanagi H (2012) Autoimmune arthritis: the interface between the immune system and joints. Adv Immunol 115:45–71. doi:10.1016/B978-0-12-394299-9.00002-3

    Article  CAS  Google Scholar 

  31. Jeong JG, Kim JM, Cho H, Hahn W, Yu SS, Kim S (2004) Effects of IL-1beta on gene expression in human rheumatoid synovial fibroblasts. Biochem Biophys Res Commun 324(1):3–7. doi:10.1016/j.bbrc.2004.09.011

    Article  CAS  Google Scholar 

  32. Miossec P, Kolls JK (2012) Targeting IL-17 and TH17 cells in chronic inflammation. Nat Rev Drug Discov 11(10):763–776. doi:10.1038/nrd3794

    Article  CAS  Google Scholar 

  33. Fossiez F, Djossou O, Chomarat P, Flores-Romo L, Ait-Yahia S, Maat C, Pin JJ, Garrone P, Garcia E, Saeland S, Blanchard D, Gaillard C, Das Mahapatra B, Rouvier E, Golstein P, Banchereau J, Lebecque S (1996) T cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic cytokines. J Exp Med 183(6):2593–2603

    Article  CAS  Google Scholar 

  34. Saxne T, Heinegard D (1992) Cartilage oligomeric matrix protein: a novel marker of cartilage turnover detectable in synovial fluid and blood. Br J Rheumatol 31(9):583–591

    Article  CAS  Google Scholar 

  35. Lai Y, Yu XP, Zhang Y, Tian Q, Song H, Mucignat MT, Perris R, Samuels J, Krasnokutsky S, Attur M, Greenberg JD, Abramson SB, Di Cesare PE, Liu CJ (2012) Enhanced COMP catabolism detected in serum of patients with arthritis and animal disease models through a novel capture ELISA. Osteoarthr Cartil 20(8):854–862. doi:10.1016/j.joca.2012.05.003

    Article  CAS  Google Scholar 

  36. Ally MM, Hodkinson B, Meyer PW, Musenge E, Tikly M, Anderson R (2013) Serum matrix metalloproteinase-3 in comparison with acute phase proteins as a marker of disease activity and radiographic damage in early rheumatoid arthritis. Mediators Inflamm 2013:183653. doi:10.1155/2013/183653

    Article  Google Scholar 

  37. Denarie D, Constant E, Thomas T, Marotte H (2014) Could biomarkers of bone, cartilage or synovium turnover be used for relapse prediction in rheumatoid arthritis patients? Mediators Inflamm 2014:537324. doi:10.1155/2014/537324

    Article  Google Scholar 

  38. Okamoto H, Yoshio T, Kaneko H, Yamanaka H (2010) Inhibition of NF-kappaB signaling by fasudil as a potential therapeutic strategy for rheumatoid arthritis. Arthritis Rheum 62(1):82–92. doi:10.1002/art.25063

    Article  CAS  Google Scholar 

  39. Molinero LL, Cubre A, Mora-Solano C, Wang Y, Alegre ML (2012) T cell receptor/CARMA1/NF-kappaB signaling controls T-helper (Th) 17 differentiation. Proc Natl Acad Sci USA 109(45):18529–18534. doi:10.1073/pnas.1204557109

    Article  CAS  Google Scholar 

  40. Hwang JK, Noh EM, Moon SJ, Kim JM, Kwon KB, Park BH, You YO, Hwang BM, Kim HJ, Kim BS, Lee SJ, Kim JS, Lee YR (2013) Emodin suppresses inflammatory responses and joint destruction in collagen-induced arthritic mice. Rheumatology 52(9):1583–1591. doi:10.1093/rheumatology/ket178

    Article  CAS  Google Scholar 

  41. Min SY, Yan M, Du Y, Wu T, Khobahy E, Kwon SR, Taneja V, Bashmakov A, Nukala S, Ye Y, Orme J, Sajitharan D, Kim HY, Mohan C (2013) Intra-articular nuclear factor-kappaB blockade ameliorates collagen-induced arthritis in mice by eliciting regulatory T cells and macrophages. Clin Exp Immunol 172(2):217–227. doi:10.1111/cei.12054

    Article  CAS  Google Scholar 

  42. Han Z, Boyle DL, Chang L, Bennett B, Karin M, Yang L, Manning AM, Firestein GS (2001) c-Jun N-terminal kinase is required for metalloproteinase expression and joint destruction in inflammatory arthritis. J Clin Investig 108(1):73–81. doi:10.1172/JCI12466

    Article  CAS  Google Scholar 

  43. Suzuki M, Tetsuka T, Yoshida S, Watanabe N, Kobayashi M, Matsui N, Okamoto T (2000) The role of p38 mitogen-activated protein kinase in IL-6 and IL-8 production from the TNF-alpha- or IL-1beta-stimulated rheumatoid synovial fibroblasts. FEBS Lett 465(1):23–27

    Article  CAS  Google Scholar 

  44. Matsumoto M, Sudo T, Saito T, Osada H, Tsujimoto M (2000) Involvement of p38 mitogen-activated protein kinase signaling pathway in osteoclastogenesis mediated by receptor activator of NF-kappa B ligand (RANKL). J Biol Chem 275(40):31155–31161. doi:10.1074/jbc.M001229200

    Article  CAS  Google Scholar 

  45. de Hooge AS, van de Loo FA, Koenders MI, Bennink MB, Arntz OJ, Kolbe T, van den Berg WB (2004) Local activation of STAT-1 and STAT-3 in the inflamed synovium during zymosan-induced arthritis: exacerbation of joint inflammation in STAT-1 gene-knockout mice. Arthritis Rheum 50(6):2014–2023. doi:10.1002/art.20302

    Article  Google Scholar 

  46. Park JS, Kwok SK, Lim MA, Kim EK, Ryu JG, Kim SM, Oh HJ, Ju JH, Park SH, Kim HY, Cho ML (2014) STA-21, a promising STAT-3 inhibitor that reciprocally regulates Th17 and Treg cells, inhibits osteoclastogenesis in mice and humans and alleviates autoimmune inflammation in an experimental model of rheumatoid arthritis. Arthritis Rheum 66(4):918–929. doi:10.1002/art.38305

    Article  CAS  Google Scholar 

  47. Bang SY, Kim JH, Kim HY, Lee YJ, Park SY, Lee SJ, Kim Y (2012) Achyranthes japonica exhibits anti-inflammatory effect via NF-kappaB suppression and HO-1 induction in macrophages. J Ethnopharmacol 144(1):109–117. doi:10.1016/j.jep.2012.08.037

    Article  Google Scholar 

  48. Minamino T, Christou H, Hsieh CM, Liu Y, Dhawan V, Abraham NG, Perrella MA, Mitsialis SA, Kourembanas S (2001) Targeted expression of heme oxygenase-1 prevents the pulmonary inflammatory and vascular responses to hypoxia. Proc Natl Acad Sci USA 98(15):8798–8803. doi:10.1073/pnas.161272598

    Article  CAS  Google Scholar 

  49. Lopez-Miranda J, Perez-Jimenez F, Ros E, De Caterina R, Badimon L, Covas MI, Escrich E, Ordovas JM, Soriguer F, Abia R, de la Lastra CA, Battino M, Corella D, Chamorro-Quiros J, Delgado-Lista J, Giugliano D, Esposito K, Estruch R, Fernandez-Real JM, Gaforio JJ, La Vecchia C, Lairon D, Lopez-Segura F, Mata P, Menendez JA, Muriana FJ, Osada J, Panagiotakos DB, Paniagua JA, Perez-Martinez P, Perona J, Peinado MA, Pineda-Priego M, Poulsen HE, Quiles JL, Ramirez-Tortosa MC, Ruano J, Serra-Majem L, Sola R, Solanas M, Solfrizzi V, de la Torre-Fornell R, Trichopoulou A, Uceda M, Villalba-Montoro JM, Villar-Ortiz JR, Visioli F, Yiannakouris N (2010) Olive oil and health: summary of the II international conference on olive oil and health consensus report, Jaen and Cordoba (Spain) 2008. Nutr Metab Cardiovasc Dis NMCD 20(4):284–294. doi:10.1016/j.numecd.2009.12.007

    Article  CAS  Google Scholar 

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Acknowledgments

This study was supported by research Grants AGL 2011-26949 (Ministerio de Economía y Competitividad, ISCIII, FEDER) and P-10AGR-6609 (Junta de Andalucía). The authors gratefully acknowledge the assistance of Center for Technology and Innovation Research, University of Seville (CITIUS). The authors thanks I+D+i de Oleoestepa SAC department who gave us the EVOO.

Conflict of interest

The authors declare that they have no conflict of interest.

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Correspondence to María Angeles Rosillo.

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Rosillo, M.A., Sánchez-Hidalgo, M., Sánchez-Fidalgo, S. et al. Dietary extra-virgin olive oil prevents inflammatory response and cartilage matrix degradation in murine collagen-induced arthritis. Eur J Nutr 55, 315–325 (2016). https://doi.org/10.1007/s00394-015-0850-0

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  • DOI: https://doi.org/10.1007/s00394-015-0850-0

Keywords

  • CIA
  • EVOO
  • Inflammatory response
  • Olive oil
  • Rheumatoid arthritis