双歧杆菌脂磷壁酸对多发性骨髓瘤患者骨髓间充质干细胞生物学特性的影响
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摘要
目的探讨双歧杆菌脂磷壁酸对多发性骨髓瘤患者骨髓间充质干细胞增殖及细胞因子分泌情况的影响。方法应用密度-梯度离心法分别获取多发性骨髓瘤患者及对照组骨髓间充质干细胞,应用流式细胞仪确定间充质干细胞表型,EDU法和ELISA法分别检测不同质量浓度(0.5、1.0、2.0、4.0、6.0g/L)的双歧杆菌脂磷壁酸共培养后的骨髓间充质干细胞增殖率及培养液上清中IL-17及IL-6含量变化。结果多发性骨髓瘤患者与对照组骨髓间充质干细胞的形态及表型表达完全相同,当双歧杆菌脂磷壁酸干预质量浓度为1.0g/L和2.0g/L时,多发性骨髓瘤组间充质干细胞的增殖率显著高于正常对照组(P<0.05),质量浓度为4.0g/L和6.0g/L时,细胞增殖率反而显著低于正常对照组(P<0.05)。多发性骨髓瘤患者骨髓间充质干细胞的IL-17和IL-6水平均显著高于正常人,应用0.5、1.0、2.0和4.0g/L双歧杆菌脂磷壁酸干预后,其细胞因子的表达水平显著下降(P<0.05)。结论一定质量浓度的双歧杆菌脂磷壁酸可以促进多发性骨髓瘤患者骨髓间充质干细胞的增殖且降低其IL-17和IL-6的表达水平。
Objective To investigate the effect of lipoteichoicacid extracted from Bacillus bifidus on the proliferation and cytokine secretion of bone marrow mesenchymal stem cells( MSCs) fom the patients with multiple myeloma. Methods The MSCs were obtained from patients with multiple myeloma and healthy people using the method of density gradient centrifugation andwere analysed by flow cytometry. Morever the proliferation and the expression of IL-17 and IL-6 in the culture medium of cellscocultured with different concentration( 0. 5,1. 0,2. 0,4. 0,6. 0 g/L) of lipoteichoicacid were tested with EDU stain and ELISA respectively. Results The morphology and phenotype of MSCsfrom patients with multiple myelomawere the same as those were obtained from the controls. The proliferation rate of MSCs in the multiple myeloma group was significantly higher than the normal group when the concentrationwas 1. 0 g/L and 2. 0 g/L( P <0. 05). However,it showed opposite performancewhen the concentrationwas 4. 0 g/L and 6. 0 g/L( P < 0. 05). The expression of IL-17 and IL-6 were significantly higher than those in control group,andwere also significantly decreased after treated with lactobacilluswith different concentration( 0. 5,1. 0,2. 0,4. 0,6. 0 g/L). Conclusion A certain concentration of bifidobacterium acid can promote the proliferation of MSCs and decrease the expression of IL-17 and IL-6 in patients with multiple myeloma.
Objective To investigate the effect of lipoteichoicacid extracted from Bacillus bifidus on the proliferation and cytokine secretion of bone marrow mesenchymal stem cells( MSCs) fom the patients with multiple myeloma. Methods The MSCs were obtained from patients with multiple myeloma and healthy people using the method of density gradient centrifugation andwere analysed by flow cytometry. Morever the proliferation and the expression of IL-17 and IL-6 in the culture medium of cellscocultured with different concentration( 0. 5,1. 0,2. 0,4. 0,6. 0 g/L) of lipoteichoicacid were tested with EDU stain and ELISA respectively. Results The morphology and phenotype of MSCsfrom patients with multiple myelomawere the same as those were obtained from the controls. The proliferation rate of MSCs in the multiple myeloma group was significantly higher than the normal group when the concentrationwas 1. 0 g/L and 2. 0 g/L( P <0. 05). However,it showed opposite performancewhen the concentrationwas 4. 0 g/L and 6. 0 g/L( P < 0. 05). The expression of IL-17 and IL-6 were significantly higher than those in control group,andwere also significantly decreased after treated with lactobacilluswith different concentration( 0. 5,1. 0,2. 0,4. 0,6. 0 g/L). Conclusion A certain concentration of bifidobacterium acid can promote the proliferation of MSCs and decrease the expression of IL-17 and IL-6 in patients with multiple myeloma.
引文
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2 李军,李炳宗,陈萍,等.硼替佐米对多发性骨髓瘤患者间充质干细胞自噬活性和成骨分化潜能的影响[J].中华内科杂志,2012,51(2):140-142
3 李炳宗,庄文卓,陈萍,等.多发性骨髓瘤患者骨髓间充质干细胞免疫调节功能异常及其在骨髓瘤骨病中的作用[J].中华微生物学和免疫学杂志,2010,9:853-859
4 Li S,Jiang Y,Li A,et al.Telomere length is positively associated with the expression of IL-6 and MIP-1αin bone marrow mesenchymal stem cells of multiple myeloma[J].Mol Med Rep,2017,16(3):2497-2504
5 付艳茹,黄少磊,龚虹,等.双歧杆菌脂磷壁酸的提取及功能的研究进展[J].中国微生态学杂志,2014,26(10):1224-1229
6 张之南,沈悌.血液病诊断及疗效标准[M].北京:科学技术出版社.2007:232-234
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8 Xu S,Menu E,De Becker A,et al.Bone marrow-derived mesenchymal stromal cells are attracted by multiple myeloma cell-produced chemokine CCL25 and favor myeloma cell growth in vitro and in vivo[J].Stem Cells,2012,30(2):266-279
9 Li X,Ling W,Khan S,et al.Therapeutic effects of intrabone and systemic mesenchymal stem cell cytotherapy on myeloma bone disease and tumor growth[J].Bone Miner Res,2012,27(8):1635-1648
10 林如峰,陆化,刘澎,等.三氧化二砷、地塞米松和沙利度胺对骨髓瘤细胞U266凋亡及胞浆内Ca2+浓度的影响[J].中国实验血液学杂志,2007,15(6):1200-1203
11 Salem DA,Korde N,Venzon DJ,et al.Expression of the IL-6 receptor alpha-chain(CD126)in normal and abnormal plasma cells in monoclonal gammopathy of undetermined significance and smoldering myeloma[J].Leuk Lymphoma,2017,25:1-9
12 张鹏宇,陈银霞,曹星梅,等.硼替佐米为主的化疗方案治疗初治多发性骨髓瘤疗效观察以及对IL-6和铁蛋白的影响[J].陕西医学杂志,2016,45(11):1511-1514
13 Prabhala RH,Pelluru D,Fulciniti M,et al.Elevated IL-17 produced by TH17 cells promotes myeloma cell growth and inhibits immune function in multiple myeloma[J].Blood,2010,115(26):5385-5392
14 张耀,宋路茜,张曦,等.多发性骨髓瘤患者外周血Th17细胞功能研究[J].中国实验血液学杂志,2013,21(5):1187-1189
15 杨云,何爱丽,王剑利,等.沙利度胺对多发性骨髓瘤患者外周血Th17细胞影响的研究[J].中国实验血液学杂志,2015,23(5):1341-1345
16 Guo B,Xie N,Wang Y.Cooperative effect of Bifidobacterialipoteichoic acid combined with 5-fluorouracil on hepatoma-22 cells growth and apoptosis[J].Bull Cancer,2015,102(3):204-212
2 李军,李炳宗,陈萍,等.硼替佐米对多发性骨髓瘤患者间充质干细胞自噬活性和成骨分化潜能的影响[J].中华内科杂志,2012,51(2):140-142
3 李炳宗,庄文卓,陈萍,等.多发性骨髓瘤患者骨髓间充质干细胞免疫调节功能异常及其在骨髓瘤骨病中的作用[J].中华微生物学和免疫学杂志,2010,9:853-859
4 Li S,Jiang Y,Li A,et al.Telomere length is positively associated with the expression of IL-6 and MIP-1αin bone marrow mesenchymal stem cells of multiple myeloma[J].Mol Med Rep,2017,16(3):2497-2504
5 付艳茹,黄少磊,龚虹,等.双歧杆菌脂磷壁酸的提取及功能的研究进展[J].中国微生态学杂志,2014,26(10):1224-1229
6 张之南,沈悌.血液病诊断及疗效标准[M].北京:科学技术出版社.2007:232-234
7 乐军,胡宏.非离子型去垢剂Tritonx-114提取两歧双歧杆菌的脂磷壁酸[J].中国微生态学杂志,1997,9(4):5-8
8 Xu S,Menu E,De Becker A,et al.Bone marrow-derived mesenchymal stromal cells are attracted by multiple myeloma cell-produced chemokine CCL25 and favor myeloma cell growth in vitro and in vivo[J].Stem Cells,2012,30(2):266-279
9 Li X,Ling W,Khan S,et al.Therapeutic effects of intrabone and systemic mesenchymal stem cell cytotherapy on myeloma bone disease and tumor growth[J].Bone Miner Res,2012,27(8):1635-1648
10 林如峰,陆化,刘澎,等.三氧化二砷、地塞米松和沙利度胺对骨髓瘤细胞U266凋亡及胞浆内Ca2+浓度的影响[J].中国实验血液学杂志,2007,15(6):1200-1203
11 Salem DA,Korde N,Venzon DJ,et al.Expression of the IL-6 receptor alpha-chain(CD126)in normal and abnormal plasma cells in monoclonal gammopathy of undetermined significance and smoldering myeloma[J].Leuk Lymphoma,2017,25:1-9
12 张鹏宇,陈银霞,曹星梅,等.硼替佐米为主的化疗方案治疗初治多发性骨髓瘤疗效观察以及对IL-6和铁蛋白的影响[J].陕西医学杂志,2016,45(11):1511-1514
13 Prabhala RH,Pelluru D,Fulciniti M,et al.Elevated IL-17 produced by TH17 cells promotes myeloma cell growth and inhibits immune function in multiple myeloma[J].Blood,2010,115(26):5385-5392
14 张耀,宋路茜,张曦,等.多发性骨髓瘤患者外周血Th17细胞功能研究[J].中国实验血液学杂志,2013,21(5):1187-1189
15 杨云,何爱丽,王剑利,等.沙利度胺对多发性骨髓瘤患者外周血Th17细胞影响的研究[J].中国实验血液学杂志,2015,23(5):1341-1345
16 Guo B,Xie N,Wang Y.Cooperative effect of Bifidobacterialipoteichoic acid combined with 5-fluorouracil on hepatoma-22 cells growth and apoptosis[J].Bull Cancer,2015,102(3):204-212