Advances in Clinical and Experimental Medicine
2018, vol. 27, nr 4, April, p. 463–468
doi: 10.17219/acem/78557
Publication type: original article
Language: English
Download citation:
Caffeine alters the effects of bone marrow-derived mesenchymal stem cells on neutrophils
1 Division of Immunology, Department of Microbiology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran
2 Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
Abstract
Background. It has been shown that mesenchymal stem cells (MSCs) express all four adenosine receptors’ subtypes, and stimulation of these receptors plays an active role in bone marrow-derived mesenchymal stem cell proliferation and differentiation. The interaction between MSCs and immunocytes, such as neutrophils, has been investigated in some recent studies.
Objectives. This study was carried out to investigate the effects of caffeine as an adenosine antagonist on the effects of bone marrow-derived MSCs on neutrophils.
Material and Methods. Mesenchymal stem cells were isolated from the bone marrow of rats and pulsed with different concentrations of caffeine (0.1, 0.5 and 1 mM) at different times (24, 48 and 72 h). Mesenchymal stem cells were co-cultured with neutrophils for 4 h and the functions of neutrophils were evaluated.
Results. The findings showed that MSCs pulsed with caffeine at low to moderate concentrations preserved the neutral red uptake by neutrophils and established the MSCs’ ability to protect neutrophils from apoptosis. Mesenchymal stem cells treated with caffeine increased the phagocytosis of neutrophils and simultaneously diminished the production of potentially harmful reactive oxygen substances, more profound than MSCs without treatment. Nevertheless, a high concentration of caffeine could interfere with some aspects of the crosstalk between MSCs and neutrophils.
Conclusion. These findings may offer new insight into the potential mechanisms underlying the immunomodulatory effects of caffeine.
Key words
neutrophil, bone marrow-mesenchymal stem cell, caffeine
References (34)
- Matissek R. Evaluation of xanthine derivatives in chocolate – nutritional and chemical aspects. Z Lebensm Unters Forsch.1997;205:175–184.
- Fredholm BB, Battig K, Holmen J, Nehlig A, Zvartau EE. Actions of caffeine in the brain with special reference to factors that contribute to its widespread use. Pharmacological Reviews.1999;51:83–133.
- Su SJ, Chang KL, Su SH, Yeh YT, Shyu HW, Chen KM. Caffeine regulates osteogenic differentiation and mineralization of primary adipose-derived stem cells and a bone marrow stromal cell line. Int J Food Sci Nutr. 2013;64:429–436.
- Schubert MM, Hall S, Leveritt M, Grant G, Sabapathy S, Desbrow B. Caffeine consumption around an exercise bout: Effects on energy expenditure, energy intake, and exercise enjoyment. J Appl Psychol. 2014;117:745–754.
- Gorska AM, Golembiowska K. The role of adenosine A1 and A2A receptors in the caffeine effect on MDMA-Induced DA and 5-HT release in the mouse striatum. Neurotoxicity Research. 2014.
- Horrigan LA, Kelly JP, Connor TJ. Immunomodulatory effects of caffeine: Friend or foe? Pharmacol Ther. 2006;111:877–892.
- Wada N, Gronthos S, Bartold PM. Immunomodulatory effects of stem cells. Periodontology 2000. 2013;63:198–216.
- Ghannam S, Bouffi C, Djouad F, Jorgensen C, Noel D. Immunosuppression by mesenchymal stem cells: Mechanisms and clinical applications. Stem Cell Res Ther. 2010;1:2.
- Meirelles Lda S, Fontes AM, Covas DT, Caplan AI. Mechanisms involved in the therapeutic properties of mesenchymal stem cells. Cytokine Growth Factor Rev. 2009;20:419–427.
- Zhang R, Liu Y, Yan K, et al. Anti-inflammatory and immunomodulatory mechanisms of mesenchymal stem cell transplantation in experimental traumatic brain injury. J Neuroinflammation. 2013;10:106.
- Esmaili Gouarchin Gale H, Delirezh N, Abtahi Froshani SM, Afzale Ahangaran N. Calcitriol modulates the effects of the supernatants of bone-marrow-derived mesenchymal stem cells on neutrophil functions. Turk J Biol. 2014;38:365–370.
- Hoogduijn MJ, Cheng A, Genever PG. Functional nicotinic and muscarinic receptors on mesenchymal stem cells. Stem Cells Development. 2009;18:103–112.
- Zhou Y, Guan XX, Zhu ZL, et al. Caffeine inhibits the viability and osteogenic differentiation of rat bone marrow-derived mesenchymal stromal cells. Br J Pharmacol. 2010;161:1542–1552.
- Katebi M, Soleimani M, Cronstein BN. Adenosine A2A receptors play an active role in mouse bone marrow-derived mesenchymal stem cell development. J Leukoc Biol. 2009;85:438–444.
- Duffy MM, Ritter T, Ceredig R, Griffin MD. Mesenchymal stem cell effects on T-cell effector pathways. Stem Cell Res Ther. 2011;2:34.
- Le Blanc K, Mougiakakos D. Multipotent mesenchymal stromal cells and the innate immune system. Nat Rev Immunol. 2012;12:383–396.
- Baghaban Eslaminejad M, Nazarian H, Taghiyar L. Mesenchymal stem cell isolation from the removed medium of rat’s bone marrow primary culture and their differentiation into skeletal cell lineages. Yakhteh Medical Journal. 2008;10:65–72.
- Abtahi Froushani SM, Delirezh N, Hobbenaghi R, Mosayebi G. Synergistic effects of atorvastatin and all-trans retinoic acid in ameliorating animal model of multiple sclerosis. Immunol Invest. 2014;43:54–68.
- Abtahi Froushani SM, Esmaili Gourvarchin Galeh H. New insight into the immunomodulatory mechanisms of Tretinoin in NMRI mice. IJBMS. 2014;17:632–637.
- Newman SL, Holly A. Candida albicans is phagocytosed, killed, and processed for antigen presentation by human dendritic cells. Infect Immun. 2001;69:6813–6822.
- Repine JE, White JG, Clawson CC, Holmes BM. Effects of phorbol myristate acetate on the metabolism and ultrastructure of neutrophils in chronic granulomatous disease. J Clin Invest. 1974;54:83–90.
- Hamaliaka A, Novikova I. Nitric oxide production disorders in leukocytes of patients with recurrent furunculosis. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2010;154:163–167.
- Gharibi B, Abraham AA, Ham J, Evans BA. Adenosine receptor subtype expression and activation influence the differentiation of mesenchymal stem cells to osteoblasts and adipocytes. J Bone Miner Res. 2011;26:2112–2124.
- Mocsai A. Diverse novel functions of neutrophils in immunity, inflammation, and beyond. J Exp Med. 2013;210:1283–1299.
- Brandau S, Jakob M, Hemeda H, et al. Tissue-resident mesenchymal stem cells attract peripheral blood neutrophils and enhance their inflammatory activity in response to microbial challenge. J Leukoc Biol. 2010;88:1005–1015.
- Crisan M, Yap S, Casteilla L, A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell. 2008,3:301–313.
- Raffaghello L, Bianchi G, Bertolotto M, et al. Human mesenchymal stem cells inhibit neutrophil apoptosis: A model for neutrophil preservation in the bone marrow niche. Stem Cells. 2008;26:151–162.
- Coxon A, Tang T, Mayadas TN. Cytokine–activated endothelial cells delay neutrophil apoptosis in vitro and in vivo. A role for granulocyte/macrophage colony-stimulating factor. J Exp Med.1999;190:923–934.
- Maqbool M, Vidyadaran S, George E, Ramasamy R. Human mesenchymal stem cells protect neutrophils from serum–deprived cell death. Cell Biol Int. 2011;35:1247–1251.
- Antal P, Sipka S, Surányi P, et al. Flow cytometric assay of phagocytic activity of human neutrophils and monocytes in whole blood by neutral red uptake. Ann Hematol.1995;70:259–265.
- Greenberg S, Grinstein S. Phagocytosis and innate immunity. Curr Opin Immunol Lett. 2002;12:136–145.
- Babior BM. Phagocytes and oxidative stress. Am J Med. 2000;109: 33–44.
- Horrigan LA, Kelly JP, Connor TJ. Caffeine suppresses TNF-alpha production via activation of the cyclic AMP/protein kinase A pathway. Int Immunopharmacol. 2004;4:1409–1417.
- Senchina DS, Hallam JE, Kohut ML, Nguyen NA, Perera MA. Alkaloids and athlete immune function: Caffeine, theophylline, gingerol, ephedrine, and their congeners. Exerc Immunol Rev. 2014;20:68–93.


