Hadi ESMAILI GOUVARCHIN GALEH, Norouz DELIREZH, Seyyed Meysam ABTAHI FROUSHANI, Nahideh AFZALE AHANGARAN

Calcitriol modulates the effects of the supernatants of bone-marrow-derived mesenchymal stem cells on neutrophil functions

Mesenchymal stem cells (MSCs) in bone marrow form a niche that has inevitable interactions with neutrophils. Moreover, previous documents have shown that calcitriol has an important role in regulating the cell growth of MSCs. This study set out to investigate the effects of calcitriol on the interaction between bone-marrow-derived MSCs and neutrophils. MSCs were isolated from the bone marrow of rats and pulsed with different concentrations of calcitriol (50, 100, and 200 nM) for different periods of time (24, 48, and 72 h). As the next step, the supernatants of MSCs cocultured with neutrophils for 4 h and neutrophil functions were evaluated. The results showed that the supernatants of MSCs treated with calcitriol could significantly increase the phagocytosis of Staphylococcus aureus by neutrophils and, conversely, decrease the respiratory burst intensity of neutrophils. Moreover, treatment of MSCs with calcitriol can cause a significant decrease in the percentage of neutrophil apoptosis. These findings were concurrent with a significant increase in IL-6 levels in the supernatant of calcitriol-treated MSCs. Consequently, the supernatant of bone-marrow-derived MSCs was pulsed with calcitriol, and the exertion of a protective role against potentially harmful reactive oxygen species production preserved phagocytosis and the survival rate of neutrophils.

Anahtar Kelimeler:

Key words: Mesenchymal stem cells, calcitriol, neutrophil

Calcitriol modulates the effects of the supernatants of bone-marrow-derived mesenchymal stem cells on neutrophil functions

Keywords:

Key words: Mesenchymal stem cells, calcitriol, neutrophil,

PDF

___

Artaza JN, Sirad F, Ferrini MG, Norris KC (2010). 1,25(OH)2vitamin D3 inhibits cell proliferation by promoting cell cycle arrest without inducing apoptosis and modifies cell morphology of mesenchymal multipotent cells. J Steroid Biochem Mol Biol 119: 73–83.
Babior BM (2000). Phagocytes and oxidative stress. Am J Med 109: 33–
Baghaban Eslaminejad M, Nazarian H, Taghiyar L (2008). 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 10: 65–72.
Brandau S, Jakob M, Hemeda H, Bruderek K, Janeschik S, Bootz F, Lang S (2010). Tissue-resident mesenchymal stem cells attract peripheral blood neutrophils and enhance their inflammatory activity in response to microbial challenge. J Leukoc Biol 88: 1005–1015.
Cantorna MT (2010). Mechanisms underlying the effect of vitamin D on the immune system. Proc Nutr Soc 69: 286–289.
Coxon A, Tang T, Mayadas TN (1999). Cytokine-activated endothelial cells delay neutrophil apoptosis in vitro and in vivo. A role for granulocyte/macrophage colony-stimulating factor. J Exp Med 190: 923–934.
Crisan M, Yap S, Casteilla L, Chen CW, Corselli M, Park TS, Andriolo G, Sun B, Zheng B, Zhang L et al. (2008). A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell 3: 301–313.
Ghannam S, Bouffi C, Djouad F, Jorgensen C, Noel D (2010). Immunosuppression by mesenchymal stem cells: mechanisms and clinical applications. Stem Cell Res Ther 1: 2.
Greenberg S, Grinstein S (2002). Phagocytosis and innate immunity. Curr Opin Immunol Lett 12: 136–145.
Hamaliaka A, Novikova I (2010). Nitric oxide production disorders in leukocytes of patients with recurrent furunculosis. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 154: 163–167.
Karaoz E, Genç ZS, Demircan PÇ, Aksoy A, Duruksu G (2010). Protection of rat pancreatic islet function and viability by coculture with rat bone marrow-derived mesenchymal stem cells. Cell Death Dis 1: e36.
Klotz B, Mentrup B, Regensburger M, Zeck S, Schneidereit J, Schupp N, Linden C, Merz C, Ebert R, Jakob F (2012). 1,25-dihydroxyvitamin D3 treatment delays cellular aging in human mesenchymal stem cells while maintaining their multipotent capacity. PLoS One 7: e29959.
Maby-El Hajjami H, Ame-Thomas P, Pangault C, Tribut O, DeVos J, Jean R, Bescher N, Monvoisin C, Dulong J, Lamy T (2009). Functional alteration of the lymphoma stromal cell niche by the cytokine context: role of indoleamine-2,3 dioxygenase. Cancer Res 69: 3228–3237.
Maqbool M, Vidyadaran S, George E, Ramasamy R (2011) Human mesenchymal stem cells protect neutrophils from serumdeprived cell death. Cell Biol Int 35: 1247–1251.
Meirelles Lda S, Fontes AM, Covas DT, Caplan AI (2009). Mechanisms involved in the therapeutic properties of mesenchymal stem cells. Cytokine Growth Factor Rev 20: 419–427.
Meisel R, Zibert A, Laryea M, Gobel U, Daubener W, Dilloo D (2004). Human bone marrow stromal cells inhibit allogeneic T-cell responses by indoleamine 2,3-dioxygenase-mediated tryptophan degradation. Blood 103: 4619–4621.
Müller J, Alföldy P, Lemmel EM (1981). Nitroblue-tetrazolium test for the functional evaluation of phagocytic cells: a critical analysis of the methodology. Agents Actions 11: 384–390.
Nabi AH, Islam LN, Rahman MM, Biswas KB (2005). Polymorphonuclear neutrophil dysfunctions in streptozotocininduced type 1 diabetic rats. J Biochem Mol Biol 38: 661–667.
Namgung R, Tsang RC, Specker BL, Sierra RI, Ho ML (1994). Low bone mineral content and high serum osteocalcin and 1,25-dihydroxyvitamin D in summer- versus winter-born newborn infants: an early fetal effect? J Pediatr Gastroenterol Nutr 19: 220–227.
Ottonello L, Tortolina G, Amelotti M, Dallegri F (1999). Soluble Fas ligand is chemotactic for human neutrophilic polymorphonuclear leukocytes. J Immunol 162: 3601–3606.
Raffaghello L, Bianchi G, Bertolotto M, Montecucco F, Busca A, Dallegri F, Ottonello L, Pistoia V (2008). Human mesenchymal stem cells inhibit neutrophil apoptosis: a model for neutrophil preservation in the bone marrow niche. Stem Cells 26: 151– 1
Rasmusson I (2006). Immune modulation by mesenchymal stem cells. Exp Cell Res Immunol 312: 2169–2179.
Ren G, Zhang L, Zhao X, Xu G, Zhang Y, Roberts AI, Zhao RC, Shi Y (2008). Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide. Cell Stem Cell 2: 141–150.
Salti GI, Grewal S, Mehta RR, Das Gupta TK, Boddie AW, Constantinou AI (2000). Genistein induces apoptosis and topoisomerase II-mediated DNA breakage in colon cancer cells. Eur J Cancer 36: 796–802.
Smyk DS, Orfanidou T, Invernizzi P, Bogdanos DP, Lenzi M (2013). Vitamin D in autoimmune liver disease. Clin Res Hepatol Gastroenterol 13: 129–139.
Turina M, Miller FN, McHugh PP, Cheadle WG, Polk HC Jr (2005). Endotoxin inhibits apoptosis but induces primary necrosis in neutrophils. Inflammation 29: 55–63.
Uccelli A, Moretta L, Pistoia V (208). Mesenchymal stem cells in health and disease. Nat Rev Immunol 8: 726–736. Zhang R, Liu Y, Yan K, Chen L, Chen XR, Li P, Chen FF, Jiang XD (2013). Anti-inflammatory and immunomodulatory mechanisms of mesenchymal stem cell transplantation in experimental traumatic brain injury. J Neuroinflammation 10: