TGF-β1对Aβ1-42诱导海马神经元-小胶质细胞共培养体系中细胞因子表达和分泌的影响

doi:10.12047/j.cjap.5668.2018.088

中国应用生理学杂志 ›› 2018, Vol. 34 ›› Issue (5): 385-388.doi: 10.12047/j.cjap.5668.2018.088

• 研究论文 • 下一篇

TGF-β1对Aβ_1-42诱导海马神经元-小胶质细胞共培养体系中细胞因子表达和分泌的影响

方小霞^1,2, 周易¹, 孙高林¹, 邱一华¹, 彭聿平¹

1. 南通大学医学院生理学系, 江苏南通 226001;
2. 南通大学机能学实验室, 江苏南通 226001

收稿日期:2018-01-05 修回日期:2018-08-02 出版日期:2018-09-28 发布日期:2019-02-21
通讯作者: 彭聿平,Tel:86-0513-85051714;E-mail:yppeng@ntu.edu.cn E-mail:yppeng@ntu.edu.cn
基金资助:
国家自然科学基金项目（31371182）；江苏省高等学校自然科学研究面上项目（18KJD310003）；江苏省教育厅研究生科研与实践创新计划项目（KYCX18_2399）

Effects of TGF-β1 on the expression and secretion of cytokines induced by Aβ_1-42 in hippocampal neuron and microglia co-cultures

FANG Xiao-xia^1,2, ZHOU Yi¹, SUN Gao-lin¹, QIU Yi-hua¹, PENG Yu-ping¹

1. Department of Physiology, School of Medicine, Nantong University, Nantong 226001, China;
2. Function Laboratory, School of Medicine, Nantong University, Nantong 226001, China

Received:2018-01-05 Revised:2018-08-02 Online:2018-09-28 Published:2019-02-21
Supported by:
国家自然科学基金项目（31371182）；江苏省高等学校自然科学研究面上项目（18KJD310003）；江苏省教育厅研究生科研与实践创新计划项目（KYCX18_2399）

摘要/Abstract

摘要： 目的：探讨在海马神经元和小胶质细胞共培养体系中转化生长因子-β1（TGF-β1）对β淀粉样肽1-42（Aβ_1-42）诱导的小胶质细胞激活表达和分泌细胞因子的影响。方法：将大鼠海马神经元和小胶质细胞进行共同培养，于共同培养后第5日，加入TGF-β1（5 or 20 ng/ml），1 h后加入Aβ_1-42（5 μmol/L），继续培养72 h后用于后续实验，Western blot法检测诱导型一氧化氮合酶（iNOS）的蛋白表达；Real-time PCR和ELISA法检测肿瘤坏死因子-α（TNF-α）、白介素-1β（IL-1β）和胰岛素样生长因子（IGF-1）的mRNA表达和分泌。结果：在共同培养的海马神经元与小胶质细胞体系中，Aβ_1-42诱导炎症因子iNOS、TNF-α和IL-1β的表达和/或分泌上调，神经营养因子IGF-1表达下调，TGF-β1预处理削弱上述Aβ_1-42的作用。结论：TGF-β1明显抑制Aβ_1-42诱导的小胶质细胞激活引起的炎性细胞因子的增加和神经营养因子的减少。

关键词: TGF-β1, Aβ_1-42, 小胶质细胞, 海马神经元, 细胞因子

Abstract: Objective: To investigate the neuroprotective effects of transforming growth factor beta 1(TGF-β1) on the expression and secretion of cytokines induced by Aβ_1-42 in hippocampal neurons and microglial co-cultures. Methods: Hippocampal neurons and microglia obtained from SD rat were co-cultured. TGF-β1 was applied on day 5 after the neurons and microglia co-cultures were incubated at the concentrations of 5 or 20 ng/ml, Aβ_1-42 was added 1 h following TGF-β1 application at a concentration of 5 μmol/L. They were incubated for 72 h and then assessed for further studies. Western blot analyses were employed to examine the expression of inducible nitric oxide synthase (iNOS); Real-time PCR and ELISA were used to detect the mRNA expression and secretion of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and insulin-like growth factor-1 (IGF-1). Results: In the hippocampal neuron-microglia co-cultures, Aβ_1-42 induced upregulation of iNOS, TNF-α and IL-1β, downregulation of IGF-1. TGF-β1 pretreatment ameliorated the pro-inflammatory effects caused by Aβ_1-42. Conclusion: TGF-β1 significantly inhibits the increase in inflammatory cytokines and the decrease in neurotrophic factor which are caused by Aβ_1-42-induced microglia activation.

Key words: TGF-β1, Aβ_1-42, microglia, hippocampal neurons, cytokines

方小霞, 周易, 孙高林, 邱一华, 彭聿平. TGF-β1对Aβ_1-42诱导海马神经元-小胶质细胞共培养体系中细胞因子表达和分泌的影响[J]. 中国应用生理学杂志, 2018, 34(5): 385-388.

FANG Xiao-xia, ZHOU Yi, SUN Gao-lin, QIU Yi-hua, PENG Yu-ping. Effects of TGF-β1 on the expression and secretion of cytokines induced by Aβ_1-42 in hippocampal neuron and microglia co-cultures[J]. CJAP, 2018, 34(5): 385-388.

参考文献

[1] Hardy J. The amyloid hypothesis for Alzheimer's disease:a critical reappraisal[J]. J Neurochem, 2009, 110(4):1129-1134.
[2] Graeber MB, Streit WJ. Microglia:biology and pathology[J]. Acta Neuropathol, 2010, 119(1):89-105.
[3] Mrak RE, Griffin WS. Glia and their cytokines in progression of neurodegeneration[J]. Neurobiol Aging, 2005, 26(3):349-354.
[4] Eikelenboom P, Rozemuller AJ, Hoozemans JJ, et al. Neuroinflammation and Alzheimer disease:clinical and therapeutic implications[J]. Alzheimer Dis Assoc Disord, 2000, 14(Suppl 1):S54-S61.
[5] Alvarez A, Cacabelos R, Sanpedro C, et al. Serum TNF-alpha levels are increased and correlate negatively with free IGF-I in Alzheimer disease[J]. Neurobiol Aging, 2007, 28(4):533-536.
[6] Matsuoka Y, Picciano M, Malester B, et al. Inflammatory responses to amyloidosis in a transgenic mouse model of Alzheimer's disease[J]. Am J Pathol, 2001, 158(4):1345-1354.
[7] Unsicker K, Strelau J. Functions of transforming growth factor-beta isoforms in the nervous system cues based on localization and experimental in vitro and in vivo evidence[J]. Eur J Biochem, 2000, 267(24):6972-6975.
[8] Komuta Y, Teng X, Yanagisawa H, et al. Expression of transforming growth factor-beta receptors in meningeal fibroblasts of the injured mouse brain[J]. Cell Mol Neurobiol, 2010, 30(1):101-111.
[9] 方小霞, 陈肖, 孙高林, 等. TGF-β1抑制Aβ1-42诱导的海马神经炎症和神经元凋亡[J]. 南通大学学报(医学版), 2015, 35(5):343-347.
[10] Jana M, Liu X, Koka S, et al. Ligation of CD40 stimulates the induction of nitric-oxide synthase in microglial cells[J]. J Biol Chem, 2001, 276(48):44527-44533.
[11] 张国霞, 周爱玲, 张贵萍, 等. 大鼠海马神经元TLR4介导的MyD88依赖途径在神经炎症中的作用[J]. 中国应用生理学杂志, 2013, 29(1):42-46.
[12] Heneka MT, Sastre M, Dumitrescu-Ozimek L, et al. Acute treatment with the PPARγ agonist pioglitazone and ibuprofen reduces glial inflammation and Aβ_1-42 levels in APPV717I transgenic mice[J]. Brain, 2005, 128(Pt 6):1442-1453.
[13] 毕燕华, 宋婷婷, 陈学群, 等. 神经肽CRH对原代大鼠皮层小胶质细胞NO、TNF-α和IL6释放的影响[J]. 中国应用生理学杂志, 2013, 29(4):323-325.
[14] Sonntag WE, Carter CS, Ikeno Y, et al. Adult-onset growth hormone and insulin-like growth factor I deficiency reduces neoplastic disease, modifies age-related pathology, and increases life span[J]. Endocrinology, 2005, 146(7):2920-2932.
[15] O'Connor JC, McCusker RH, Strle K, et al. Regulation of IGF-I function by proinflammatory cytokines:at the interface of immunology and endocrinology[J]. Cell Immunol, 2008, 252(1-2):91-110.
[16] Dantzer R, O'Connor J, Freund G, et al. From inflammation to sickness and depression:when the immune system subjugates the brain[J]. Nat Rev Neurosci, 2008, 9(1):46-56.
[17] Zhu Y, Chen X, Liu Z, et al. Interleukin-10 protection against lipopolysaccharide-induced neuro-inflammation and neurotoxicity in ventral mesencephalic cultures[J]. Int J Mol Sci, 2015, 17(1):25-39.
[18] Caraci F, Spampinato S, Sortino MA, et al. Dysfunction of TGF-beta1 signaling in Alzheimer's disease:perspectives for neuroprotection[J]. Cell Tissue Res, 2012, 347(1):291-301.
[19] Vivien D, Ali C. Transforming growth factor-beta signaling in brain disorders[J]. Cytokine Growth Factor Rev, 2006, 17(1-2):121-128.

TGF-β1对Aβ_1-42诱导海马神经元-小胶质细胞共培养体系中细胞因子表达和分泌的影响

Effects of TGF-β1 on the expression and secretion of cytokines induced by Aβ_1-42 in hippocampal neuron and microglia co-cultures

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	王凌星, 洪姗燕, 杨美丽, 黄红红. 丁苯酞对睡眠剥夺大鼠额叶小胶质细胞活化的影响^*[J]. 中国应用生理学杂志, 2020, 36(2): 106-110.
[2]	蒋盼若, 楼恩哲, 赵智祥, 徐炯楠, 郑晓菲, 柯瑞君, 陈佳玉. 芹菜多糖抑制小鼠肺癌的作用研究^*[J]. 中国应用生理学杂志, 2019, 35(6): 551-554.
[3]	买买提·依斯热依力, 艾克拜尔·艾力, 买买提艾力·艾则孜, 吾布力卡斯木·吾拉木, 李义亮, 阿孜古丽·阿力木江, 闫晶, 克力木·阿不都热依木. 心理应激对小鼠脂肪组织黄嘌呤氧化酶表达、活性及相关指标的影响^*[J]. 中国应用生理学杂志, 2019, 35(6): 537-542.
[4]	程鋆, 鲁萌萌, 张阳, 高凌云, 陈超, 蒋慧心, 刘平, 黄秀雯, 刘云路. 二甲双胍对D-半乳糖诱导雄性中年小鼠衰老的干预作用^*[J]. 中国应用生理学杂志, 2019, 35(5): 433-437.
[5]	章书豪, 邵思铭, 陈方政, 祝静, 陈罗薇, 王恒, 项歆惠, 袁琳波. 苹果多酚对野百合碱诱导的肺动脉高压大鼠肺血管重构的作用和机制^*[J]. 中国应用生理学杂志, 2019, 35(3): 209-214.
[6]	刘煜鑫, 闫东. 右美托咪定对大鼠海马神经元生长发育的影响及其机制[J]. 中国应用生理学杂志, 2019, 35(1): 69-73.
[7]	柳卓, 刘检, 凌佳, 杨琴, 杨蕙, 孟盼, 杜青, 赵洪庆, 王宇红. ELK-1/JNK/c-Fos对左归降糖解郁方(ZGJTJYF)体外培养的模拟糖尿病并发抑郁症(DD)大鼠海马神经元凋亡中的作用[J]. 中国应用生理学杂志, 2019, 35(1): 50-54.
[8]	陈彦凡, 何以成, 黄卡特, 虞晓明, 陈马云, 陈相, 黄晓颖, 王良兴. 腺苷A_2a受体在博莱霉素诱导的小鼠肺纤维化中的作用[J]. 中国应用生理学杂志, 2018, 34(3): 204-208.
[9]	马洁, 郭康, 吕林亚, 李新娟, 王璐, 魏林郁, 赵红岗, 李东亮. NaHS对ATP诱导大鼠小胶质细胞P2X受体表达的影响[J]. 中国应用生理学杂志, 2017, 33(6): 519-523.
[10]	刚琳, 李一鹏, 卢磊, 杨凯, 孙中磊, 陈旭义, 涂悦. Slit 2N与丝素蛋白混合物诱导大鼠海马神经元迁移的体外模型建立[J]. 中国应用生理学杂志, 2017, 33(5): 445-449.
[11]	马益梅, 李传达, 朱雅冰, 徐霞, 李军, 曹红. RvD1对大鼠2型糖尿病神经病理性痛的作用及机制研究[J]. 中国应用生理学杂志, 2017, 33(3): 277-281.
[12]	李平, 张巧莲, 李双英. 卒中后抑郁与血清炎性细胞因子水平及神经功能损害的相关性分析[J]. 中国应用生理学杂志, 2017, 33(2): 121-123.
[13]	蒋伟, 张弦, 周爱玲. TLR₄/P38/JNK信号通路在海马神经元凋亡中的作用[J]. 中国应用生理学杂志, 2016, 32(6): 571-576.
[14]	袁小涌, 王超, 孙凤仙, 徐淑梅. β片层阻断肽H102对双转基因AD小鼠突触可塑性相关蛋白的影响[J]. 中国应用生理学杂志, 2016, 32(4): 293-298.
[15]	张余, 刘英富, 陈旭义, 涂悦, 梁冰, 徐忠伟, 赵永青. 阿糖胞苷对大鼠海马神经元原代培养的影响[J]. 中国应用生理学杂志, 2016, 32(3): 218-220.

TGF-β1对Aβ1-42诱导海马神经元-小胶质细胞共培养体系中细胞因子表达和分泌的影响

Effects of TGF-β1 on the expression and secretion of cytokines induced by Aβ1-42 in hippocampal neuron and microglia co-cultures

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

TGF-β1对Aβ_1-42诱导海马神经元-小胶质细胞共培养体系中细胞因子表达和分泌的影响

Effects of TGF-β1 on the expression and secretion of cytokines induced by Aβ_1-42 in hippocampal neuron and microglia co-cultures