[1]李赛赛,王潇雨,高擎,等.GDNF重塑BV2细胞对胶质瘤相关因子的分泌能力[J].徐州医科大学学报,2020,40(10):735-740.[doi:10.3969/j.issn.2096-3882.2020.10.007]
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GDNF重塑BV2细胞对胶质瘤相关因子的分泌能力()
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《徐州医科大学学报》[ISSN:2096-3882/CN:32-1875/R]

卷:
40
期数:
2020年10期
页码:
735-740
栏目:
出版日期:
2020-10-25

文章信息/Info

Title:
GDNF remodels BV2 cells to secrete glioma-related factors
作者:
李赛赛 王潇雨 高擎 荣玉如 张宝乐
徐州医科大学神经生物学重点实验室,江苏 徐州 221004;徐州医科大学临床医学系,江苏 徐州 221002;徐州医科大学神经生物学重点实验室,江苏 徐州 221004
关键词:
胶质细胞系源性神经营养因子 小胶质细胞 细胞因子 胶质瘤 肿瘤微环境
DOI:
10.3969/j.issn.2096-3882.2020.10.007
文献标志码:
A
摘要:
目的 明确胶质细胞系源性神经营养因子(GDNF)对小鼠BV2小胶质细胞分泌肿瘤相关细胞因子的影响。方法 采用0、50、100、200和500 ng/ml GDNF分别处理BV2细胞12、24、36和48 h。Real-time PCR检测各组细胞中肿瘤抑制因子(TNF-α、IFN-β和IL-10)和肿瘤促进因子(IL-1β、TGF-β、HGF和MMP9)的mRNA水平;酶联免疫吸附试验(ELISA)验证TNF-α、IFN-β和IL-1β的蛋白分泌水平。利用GDNF和GFR-α1的中和抗体处理BV2细胞,并利用ELISA检测IL-1β蛋白的分泌量。结果 GDNF显著抑制TNF-α 和IFN-β的mRNA表达的同时,显著升高IL-1β、TGF-β和MMP9的mRNA表达(P < 0.05 )。IL-1β、TNF-α和IFN-β的蛋白分泌水平与mRNA结果一致。GDNF和GFR-α1的中和抗体均显著抑制了IL-1β蛋白的分泌,且中和GFR-α1显著抑制了GDNF诱导的IL-1β蛋白的分泌(P < 0.05 )。结论 GDNF 处理的小胶质细胞高分泌肿瘤促进因子、低分泌肿瘤抑制因子,阻断GFR-α1能够抑制GDNF诱导的IL-1β蛋白分泌,提示GDNF可能经GFR-α1介导的信号通路重塑肿瘤微环境进而促进胶质瘤的发展。
Abstract:
ob<x>jective This study aims to clarify that the effects of glial cell line-derived neurotrophic factor (GDNF) on mouse BV2 microglia to secrete tumor-related factors. Methods BV 2 cells were treated with 0, 50, 100, 200 and 500 ng/ml GDNF for 12, 24, 36 and 48 h. Real-time PCR was used to detect the mRNA ex<x>pression levels of tumor suppressor factors (TNF-α, IFN-β and IL-10) and tumor promoting factors (IL-1β, TGF-β, HGF and MMP9); enzyme-li<x>nked immunosorbent assay (ELISA) was used to verify the protein secretion of TNF-α, IFN-β and IL-1β. The neutralizing antibody of GDNF or GFR-α1 w as used to treat BV2 cells, and the secretion of IL-1β protein was detected by ELISA. Results GDNF significantly reduced the TNF-α and IFN-β mRNA ex<x>pression, while significantly increased the IL-1β, TGF-β, MMP9 and IL-10 mRNA ex<x>pression in BV2 cells ( P < 0.05) . Moreover, the protein secretion of TNF-α, IFN-β and IL-1β were consistent with the mRNA ex<x>pression. Both GDNF and GFR-α1 neutralizing antibodies significantly inhibited the secretion of IL-1β protein, and neutralizing GFR-α1 significantly inhibited the secretion of IL-1β protein induced by GDNF (P <0.05). Conclusions GDNF -treated BV2 microglia secreted high levels of tumor promoting factors and low levels of tumor suppressor factors, and blocking GFR-α1 inhibited GDNF -induced IL-1β protein secretion, indicating that GDNF may remold the tumor microenvironment via GFR-α1 mediated signaling pathways in microglia to promote the glioma progression.

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更新日期/Last Update: 2020-11-04