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1Secretion of immunoregulatory cytokines by mesenchymal stem cells显示文摘According to the minimal criteria of the International Society of Cellular Therapy, mesenchymal stem cells(MSCs) are a population of undifferentiated cells defined by their ability to adhere to plastic surfaces when cultured under standard conditions, express a certain panel of phenotypic markers and can differentiate into osteogenic, chondrogenic and adipogenic lineages when cultured in specific inducing media. In parallel with their major role as undifferentiated cell reserves, MSCs have immunomodulatory functions which are exerted by direct cell-to-cell contacts, secretion of cytokines and/or by a combination of both mechanisms. There are no convincing data about a principal difference in the profile of cytokines secreted by MSCs isolated from different tissue sources, although some papers report some quantitative but not qualitative differences in cytokine secretion. The present review focuses on the basic cytokines secreted by MSCs as described in the literature by which the MSCs exert immunodulatory effects. It should be pointed out that MSCs themselves are objects of cytokine regulation. Hypothetical mechanisms by which the MSCs exert their immunoregulatory effects are also discussed in this review. These mechanisms may either influence the target immune cells directly or indirectly by affecting the activities of predominantly dendritic cells. Chemokines are also discussed as participants in this process by recruiting cells of the immune systems and thus making them targets of immunosuppression. This review aims to present and discuss the published data and the personal experience of the authors regarding cytokines secreted by MSCs and their effects on the cells of the immune system.Dobroslav Kyurkchiev Ivan Bochev Ekaterina Ivanova-Todorova Milena Mourdjeva Tsvetelina Oreshkova Kalina Belemezova Stanimir Kyurkchiev 2014World Journal of Stem Cells2014,6,5:20
2Treg/Th17 cell balance and phytohaemagglutinin activation of T lymphocytes in peripheral blood of systemic sclerosis patients显示文摘AIM To investigate T-cell activation, the percentage of peripheral T regulatory cells(Tregs), Th17 cells and the circulating cytokine profile in systemic sclerosis(SSc).METHODS We enrolled a total of 24 SSc patients and 16 healthy controls in the study and divided the patients as having diffuse cutaneous SSc(dc SSc, n = 13) or limited cutaneous SSc(lc SSc, n = 11). We performed a further subdivision of the patients regarding the stage of the disease-early, intermediate or late. Peripheral venous blood samples were collected from all subjects. We performed flow cytometric analysis of the activationcapacity of T-lymphocytes upon stimulation with PHA-M and of the percentage of peripheral Tregs and Th17 cells in both patients and healthy controls. We used ELISA to quantitate serum levels of human interleukin(IL)-6, IL-10, tissue growth factor-β1(TGF-β1), and IL-17 A.RESULTS We identified a decreased percentage of CD3+CD69+ cells in PHA-stimulated samples from SSc patients in comparison with healthy controls(13.35% ± 2.90% vs 37.03% ± 2.33%, P < 0.001). However, we did not establish a correlation between the down-regulated CD3+CD69+ cells and the clinical subset, nor regarding the stage of the disease. The activated CD4+CD25+ peripheral lymphocytes were represented in decreased percentage in patients when compared to controls(6.30% ± 0.68% vs 9.36% ± 1.08%, P = 0.016). Regarding the forms of the disease, dc SSc patients demonstrated lower frequency of CD4+CD25+ T cells against healthy subjects(5.95% ± 0.89% vs 9.36% ± 1.08%, P = 0.025). With regard to Th17 cells, our patients demonstrated increased percentage in comparison with controls(18.13% ± 1.55% vs 13.73% ± 1.21%, P = 0.031). We detected up-regulated Th17 cells within the lc SSc subset against controls(20.46% ± 2.41% vs 13.73% ± 1.21%, P = 0.025), nevertheless no difference was found between dc SSc and lc SSc patients. Flow cytometric analysis revealed an increased percentage of CD4+CD25-Foxp3+ in dc SSc patients compared to controls(10.94% ± 1.65% vs 6.88% ± 0.91, P = 0.032). Regarding the peripheral cytokine profile, we detected raised levels of IL-6 [2.10(1.05-4.60) pg/m L vs 0.00 pg/m L, P < 0.001], TGF-β1(19.94 ± 3.35 ng/m L vs 10.03 ± 2.25 ng/m L, P = 0.02), IL-10(2.83 ± 0.44 pg/m L vs 0.68 ± 0.51 pg/m L, P = 0.008), and IL-17 A [6.30(2.50-15.60) pg/m L vs 0(0.00-0.05) pg/m L, P < 0.001] in patients when compared to healthy controls. Furthermore, we found increased circulating IL-10, TGF-β, IL-6 and IL-17 A in the lc SSc subset vs control subjects, as it follows: IL-10(3.32 ± 0.59 pg/m L vs 0.68 ± 0.51 pg/m L, P = 0.003), TGF-β1(22.82 ± 4.99 ng/m L vs 10.03 ± 2.25 ng/m L, P = 0.031), IL-6 [2.08(1.51-4.69) pg/m L vs 0.00 pg/m L, P < 0.001], and IL-17 A [14.50(8.55-41.65) pg/m L vs 0.00(0.00-0.05) pg/m L, P < 0.001]. Furthermore, circulating IL-17 A was higher in lc SSc as opposed to dc SSc subset(31.99 ± 13.29 pg/m L vs 7.14 ± 3.01 pg/m L, P = 0.008). Within the dc SSc subset, raised levels of IL-17 A and IL-6 were detected vs healthy controls: IL-17 A [2.60(0.45-9.80) pg/m L vs 0.00(0.00-0.05) pg/m L, P < 0.001], IL-6 [2.80(1.03-7.23) pg/m L vs 0.00 pg/m L, P < 0.001]. Regarding the stages of the disease, TGF-β1 serum levels were increased in early stage against late stage, independently from the SSc phenotype(30.03 ± 4.59 ng/m L vs 13.08 ± 4.50 ng/m L, P = 0.017).CONCLUSION It is likely that the altered percentage of Th17 and CD4+CD25-Fox P3+ cells along with the peripheral cytokine profile in patients with SSc may play a key role in the pathogenesis of the disease.Ekaterina Krasimirova Tsvetelina Velikova Ekaterina Ivanova-Todorova Kalina Tumangelova-Yuzeir Desislava Kalinova Vladimira Boyadzhieva Nikolay Stoilov Tsvetelina Yoneva Rasho Rashkov Dobroslav Kyurkchiev 2017World Journal of Experimental Medicine2017,7,3:10
3HLA-G expression is up-regulated by progesterone in mes-enchymal stem cells显示文摘Ivanova-Todorova E Mourdjeva M Kyurkchiev D 2009Am J Reprod Immunol2009,62,:1
4Pre-decidual multipotent stromal cells(preDMSC)consti-tutively express progesterone induced blocking factor(PIBF)显示文摘Ivanova-Todorova E Kyurkchiev D Mourdjeva M 2009C R Acad Bulg Sci2009,62,:1
5Female sex steroid hormones modify some regulatory proper- ties of monocyte-derived dendritic cells显示文摘Kyurkchiev D Ivanova-Todorova E Hayrabedyan S 2007Am J Reprod Im- munol2007,58,5:1
6Purification and characterization of sperm coating antigen identified by monoclonal antibody显示文摘Diomitrova D Kehayov I Kyurkchiev S 1993Andrology1993,25,5:1
7FGF-1 and S100A13 possibly contribute to angiogenesis in endometriosis显示文摘Hayrabedyan S Kyurkchiev S Kehayov I 2005J Reprod Immunol2005,67,12:1
8FGF-1 and S100A13 possibly contribute to angiogenesis in endometriosis 显示文摘Hayrabedyan S Kyurkchiev S Kehayov I 2005J Reprod Immunol2005,67,12:1
9Characterization of elo- nogenie stromal cells isolated from human endometrium 显示文摘Dimitrov R Timeva T Kyurkchiev D 2008Repro- duction2008,135,:1
10Characterization of elonogenie stromal cells isolated from human endometrium显示文摘Mitrov R Timeva T Kyurkchiev D 2008Reproduction2008,135,4:1
11Endoglin (cd105) and S100A13 as markers of active angiogenesis in endometriosis显示文摘Hayrabedyan S Kyurkchiev S Kehayov I 2005Reprod Biol2005,5,1:1
12Recurrentimplantation, failure: the role of the endometrium 显示文摘Timeva T Shterev A Kyurkchiev S 2014JReprod Infertile2014,15,:1
13Assessment of presence and characteristics of multipotent stromal cells in human endometrium and decidua显示文摘Kyurkchiev S Shterev A Dimitrov R 2010Reprod Biomed2010,20,3:1
14Immunohistochemical detection of atrial natriuretic factor (ANF) in different ovarian cell types显示文摘Russinova A Mourdjeva M Kyurkchiev S 2001Endoer Regul2001,35,:1
15Production and characterization of a novel monoclonal antibody against progesterone-induced blocking factor (PIBF)显示文摘Ivanova-Todorova E Kyurkchiev DS Nalbanski A 2008J Reprod Immunol2008,78,2:1
16Assessment of presence and characteristics of multipotent stromal cel s in human endometrium and decidua显示文摘Kyurkchiev S Shterev A Dimitrov R 0,,03:1
17Characteriza- tion of mesenchymal stem ceils isolated from the human umbilical cord显示文摘Kestendjieva S Kyurkchiev D Tsvetkova G 2008Cell Biol Int2008,32,7:1
18Effect of Progesterone on Human Mesenchymal Stem Cells显示文摘Dobroslav S. Kyurkchiev Ekaterina Ivanova-Todorova Stanimir D. Kyurkchiev 2011Vitamins and Hormones2011,,:1
19Characterization of clonogenic stromal cells isolated from human endometrium 显示文摘Dimitrov R Timeva T Kyurkchiev D 2008Reproduction2008,135,4:1
20Triehinella spiralis: a 76 kDa excretory/secretory larval antigen identified by monoclonal antibody显示文摘Kehayov IR Kyurkchiev SD Tankov CV 1991Exp Parasitol1991,73,:1
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