Ukr.Biochem.J. 2016; Volume 88, Issue 3, May-Jun, pp. 83-91

doi: https://doi.org/10.15407/ubj88.03.083

Effect of curcumin on accumulation in mononuclear cells and secretion in incubation medium of Аβ(40) and cytokines under local excess of Аβ(42)-homoaggregates

V. V. Sokolik1, S. M. Shulga2

1SI “Institute of Neurology, Psychiatry and Narcology of NAMS of Ukraine”, Kharkiv;
2SI “Institute for Food Biotechnology and Genomics of NAS of Ukraine”, Kyiv;
e-mail:  sokolik67@rambler.ru

The aim of the work was to investigate accumulation of endogenous Aβ40 and cytokines (IL-1β, TNFα, IL-6, IL-10) in mononuclear cells and their secretion into incubation medium under Aβ42-aggregates’ toxicity and anti-inflammatory effects of curcumin. Mononuclear cells were isolated in Ficoll-Urografin density gradient from venous blood of healthy donors, resuspended and used for testing of homoaggregates of Aβ42 (15 nM), curcumin (54 pM) and their combinations on various timescales (0, 1, 2, 3, 6 and 24 hours). Endogenous Aβ40 and cytokines were detected in mononuclear cells and (separately) in incubation medium by ELISA. We demonstrated for the first time that homoaggregates of Aβ42 cause rapid accumulation of endogenous Aβ40 in mononuclear cells and accelerate its secretion into incubation medium. We found increased concentration of TNFα after 3 hours of incubation, and no changes in IL-1β concentration due to secretion of these pro-inflammatory factors into incubation medium. The concentrations of IL-6 in mononuclear cells were increased under effects of Aβ42 homoaggregates, and it was being secreted profoundly into incubation medium. Aβ42 did not affect IL-10 secretion, yet caused an increase in its intracellular concentration after 1 hour of incubation, which was subsequently suppressed. Curcumin prevented the increase in Aβ40 concentration in mononuclear cells and significantly decreased its secretion resulting from Aβ42 toxicity. Curcumin negated the activating effect of Aβ42 on pro-inflammatory cytokines, starting immediately for IL-1β and on 3-6 hours for TNFα, which resulted in decreased extracellular concentrations of these cytokines. The polyphenol also potentiated repleni­shing of intracellular IL-6 and IL-10 concentrations and their secretion into incubation medium.

Keywords: , , , ,


References:

  1. De-Paula VJ, Radanovic M, Diniz BS, Forlenza OV. Alzheimer’s disease. Subcell Biochem. 2012;65:329-52. Review. PubMed, CrossRef
  2. Selkoe DJ. Toward a comprehensive theory for Alzheimer’s disease. Hypothesis: Alzheimer’s disease is caused by the cerebral accumulation and cytotoxicity of amyloid beta-protein. Ann N Y Acad Sci. 2000;924:17-25. Review. PubMed, CrossRef
  3. Querfurth HW, LaFerla FM. Alzheimer’s disease. N Engl J Med. 2010 Jan 28;362(4):329-44. PubMed, CrossRef
  4. Crouch PJ, Harding SM, White AR, Camakaris J, Bush AI, Masters CL. Mechanisms of A beta mediated neurodegeneration in Alzheimer’s disease. Int J Biochem Cell Biol. 2008;40(2):181-98. PubMed
  5. Haass C, Selkoe DJ. Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer’s amyloid beta-peptide. Nat Rev Mol Cell Biol. 2007 Feb;8(2):101-12. PubMed, CrossRef
  6. Yankner BA, Lu T. Amyloid beta-protein toxicity and the pathogenesis of Alzheimer disease. J Biol Chem. 2009 Feb 20;284(8):4755-9. Review. PubMed, PubMedCentral, CrossRef
  7. Pearson HA, Peers C. Physiological roles for amyloid beta peptides. J Physiol. 2006 Aug 15;575(Pt 1):5-10. Review. PubMed, PubMedCentral, CrossRef
  8. Soscia SJ, Kirby JE, Washicosky KJ, Tucker SM, Ingelsson M, Hyman B, Burton MA, Goldstein LE, Duong S, Tanzi RE, Moir RD. The Alzheimer’s disease-associated amyloid beta-protein is an antimicrobial peptide. PLoS One. 2010 Mar 3;5(3):e9505. PubMed, PubMedCentral, CrossRef
  9. Sokolik VV, Maltsev AV. Cytokines neuroinflammatory reaction to the action of homoaggregatic and liposomal forms of b-amyloid 1-40 in rats. Biomed Khim. 2015 May-Jun;61(3):373-80. (In Russian). PubMed, CrossRef
  10. Mehta PD, Pirttilä T, Mehta SP, Sersen EA, Aisen PS, Wisniewski HM. Plasma and cerebrospinal fluid levels of amyloid beta proteins 1-40 and 1-42 in Alzheimer disease. Arch Neurol. 2000 Jan;57(1):100-5. PubMedCrossRef
  11. Roher AE, Esh CL, Kokjohn TA, Castaño EM, Van Vickle GD, Kalback WM, Patton RL, Luehrs DC, Daugs ID, Kuo YM, Emmerling MR, Soares H, Quinn JF, Kaye J, Connor DJ, Silverberg NB, Adler CH, Seward JD, Beach TG, Sabbagh MN. Amyloid beta peptides in human plasma and tissues and their significance for Alzheimer’s disease. Alzheimers Dement. 2009 Jan;5(1):18-29.  PubMed, PubMedCentral, CrossRef
  12. Toledo JB, Shaw LM, Trojanowski JQ. Plasma amyloid beta measurements – a desired but elusive Alzheimer’s disease biomarker. Alzheimers Res Ther. 2013 Mar 8;5(2):8. eCollection 2013. Review. PubMedPubMedCentral, CrossRef
  13. Hansson O, Zetterberg H, Vanmechelen E, Vanderstichele H, Andreasson U, Londos E, Wallin A, Minthon L, Blennow K. Evaluation of plasma Abeta(40) and Abeta(42) as predictors of conversion to Alzheimer’s disease in patients with mild cognitive impairment. Neurobiol Aging. 2010 Mar;31(3):357-67. PubMed, CrossRef
  14. Le Bastard N, Leurs J, Blomme W, De Deyn PP, Engelborghs S.  Plasma amyloid-beta forms in Alzheimer’s disease and non-Alzheimer’s disease patients. J Alzheimers Dis. 2010;21(1):291-301. PubMed
  15. Boutajangout A, Wisniewski T. The innate immune system in Alzheimer’s disease. Int J Cell Biol. 2013;2013:576383. PubMedPubMedCentralCrossRef
  16. Sokolik VV, Koliada OK, Shulga SM. Effect of β-amyloid peptide 42 on the dynamics of expression and formation of Аβ40, IL-1β, TNFα, IL-6, IL-10 by peripheral blood mononuclear cells in vitro and its correction by curcumin. Ukr Biochem J. 2016;88(1):109-118. CrossRef
  17. Sokolik VV, Shulga SM.  Influence of curcumin on cytokines content and angiotensin-converting activity under intrahippocampus administration of β-amyloid peptide in rats. Biotechnologia Acta. 2015;8(3):78-88. CrossRef
  18. Sokolik VV, Shulga SM. Effect of curcumin liposomal form on angiotensin converting activity, cytokines and cognitive characteristics of the rats with Alzheimer’s disease model. Biotechnologia Acta. 2015;8(6):48-55. CrossRef
  19. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265-75. PubMed
  20. Xiong Z, Hongmei Z, Lu S, Yu L. Curcumin mediates presenilin-1 activity to reduce β-amyloid production in a model of Alzheimer’s Disease. Pharmacol Rep. 2011;63(5):1101-8. PubMed, CrossRef
  21. Twomey C, McCarthy JV. Presenilin-1 is an unprimed glycogen synthase kinase-3beta substrate. FEBS Lett. 2006 Jul 24;580(17):4015-20.  PubMed, CrossRef
  22. Wang HM, Zhao YX, Zhang S, Liu GD, Kang WY, Tang HD, Ding JQ, Chen SD. PPARgamma agonist curcumin reduces the amyloid-beta-stimulated inflammatory responses in primary astrocytes. J Alzheimers Dis. 2010;20(4):1189-99. PubMed
  23. Zhang C, Browne A, Child D, Tanzi RE. Curcumin decreases amyloid-beta peptide levels by attenuating the maturation of amyloid-beta precursor protein. J Biol Chem. 2010 Sep 10;285(37):28472-80. PubMedPubMedCentral, CrossRef
  24. Tocci MJ. Structure and function of interleukin-1 beta converting enzyme. Vitam Horm. 1997;53:27-63. PubMedCrossRef
  25. Lu XJ, Chen Q, Yang GJ, Chen J. The TNFα converting enzyme (TACE) from ayu (Plecoglossus altivelis) exhibits TNFα shedding activity. Mol Immunol. 2015 Feb;63(2):497-504. PubMedCrossRef
  26. De Strooper B, Annaert W. Proteolytic processing and cell biological functions of the amyloid precursor protein. J Cell Sci. 2000 Jun;113(Pt 11):1857-70. PubMed
  27. Ito A, Mukaiyama A, Itoh Y, Nagase H, Thogersen IB, Enghild JJ, Sasaguri Y, Mori Y. Degradation of interleukin 1beta by matrix metalloproteinases. J Biol Chem. 1996 Jun 21;271(25):14657-60. PubMed, CrossRef
  28. Sedger LM, McDermott MF. TNF and TNF-receptors: From mediators of cell death and inflammation to therapeutic giants – past, present and future. Cytokine Growth Factor Rev. 2014 Aug;25(4):453-72.  PubMed, CrossRef
  29. Khar A, Ali AM, Pardhasaradhi BV, Begum Z, Anjum R. Antitumor activity of curcumin is mediated through the induction of apoptosis in AK-5 tumor cells. FEBS Lett. 1999 Feb 19;445(1):165-8. PubMedCrossRef
  30. Abe Y, Hashimoto S, Horie T. Curcumin inhibition of inflammatory cytokine production by human peripheral blood monocytes and alveolar macrophages. Pharmacol Res. 1999 Jan;39(1):41-7. PubMed, CrossRef
  31. Jurenka JS. Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: a review of preclinical and clinical research. Altern Med Rev. 2009 Jun;14(2):141-53. PubMed
  32. Epstein J, Docena G, MacDonald TT, Sanderson IR. Curcumin suppresses p38 mitogen-activated protein kinase activation, reduces IL-1beta and matrix metalloproteinase-3 and enhances IL-10 in the mucosa of children and adults with inflammatory bowel disease. Br J Nutr. 2010 Mar;103(6):824-32.  PubMed, CrossRef
  33. Song WB, Wang YY, Meng FS, Zhang QH, Zeng JY, Xiao LP, Yu XP, Peng DD, Su L, Xiao B, Zhang ZS. Curcumin protects intestinal mucosal barrier function of rat enteritis via activation of MKP-1 and attenuation of p38 and NF-κB activation. PLoS One. 2010 Sep 24;5(9):e12969. PubMed, PubMedCentral, CrossRef

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