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肾上腺髓质素在幽门螺杆菌感染中的表达调控及其功能的初步研究
Role and mechanism of adrenomedullin expression in
Helicobacter pylori infection- 第三军医大学学报 2018年40卷第3期 页码：183-189
- 作者机构：
重庆，陆军军医大学(第三军医大学)药学与检验医学系微生物与生化药学教研室
- 作者简介：
[ 庄园，E-mail：yuanzhuang1983@yahoo.com ZHUANG Yuan, E-mail: yuanzhuang1983@yahoo.com
[ 郭刚，E-mail：guogang7001@163.com GUO Gang, E-mail: guogang7001@163.com
- 基金信息：国家自然科学基金面上项目(81670510)
DOI：10.16016/j.1000-5404.201709041
中图分类号： R377;R392.3;R573.02收稿：2017-09-06，
修回：2017-11-14，
纸质出版：2018-02-15
- 稿件说明：
移动端阅览
孔辉, 庄园, 毛方圆, 等. 肾上腺髓质素在幽门螺杆菌感染中的表达调控及其功能的初步研究[J]. 第三军医大学学报, 2018,40(3):183-189.
Hui KONG, Yuan ZHUANG, Fangyuan MAO, et al. Role and mechanism of adrenomedullin expression in
Helicobacter pylori infection[J]. Journal of Third Military Medical University, 2018, 40(3): 183-189.孔辉, 庄园, 毛方圆, 等. 肾上腺髓质素在幽门螺杆菌感染中的表达调控及其功能的初步研究[J]. 第三军医大学学报, 2018,40(3):183-189. DOI： 10.16016/j.1000-5404.201709041.
Hui KONG, Yuan ZHUANG, Fangyuan MAO, et al. Role and mechanism of adrenomedullin expression in
Helicobacter pylori infection[J]. Journal of Third Military Medical University, 2018, 40(3): 183-189. DOI： 10.16016/j.1000-5404.201709041.
摘要
目的
2
探讨肾上腺髓质素(adrenomedullin
ADM)在幽门螺杆菌感染中的表达调控及其对CD3
+
T细胞增殖的影响。
方法
2
建立幽门螺杆菌(
Helicobacter pylori
H.pylori
)感染C57小鼠及胃上皮细胞模型，运用定量PCR、免疫组织化学染色和Western blot检测ADM的表达；并在细胞模型中探讨
H.pylori
感染诱导ADM上调的机制；利用ADM刺激CD3
+
T细胞，检测其对T细胞增殖的影响。
结果
2
H.pylori
感染可诱导胃上皮细胞AGS和HGC-27上调ADM的表达，并具有时间和感染菌量依赖性(
P
<
0.05)；PI3K/AKT信号通路阻断可显著抑制
H.pylori
感染诱导的ADM上调表达(
P
<
0.05)；相对于未感染组，
H.pylori
感染小鼠胃组织中的ADM水平也显著增高；而相对于野生型全毒株，敲除cagA基因后，
H.pylori
感染诱导ADM上调的能力则显著下降(
P
<
0.05)；ADM能够以剂量依赖的方式诱导CD3
+
T细胞的增殖并促进IFN-γ的表达(
P
<
0.05)。
结论
2
幽门螺杆菌感染可经PI3K/AKT信号诱导肾上腺髓质素的表达上调，后者则可能通过影响CD3
+
T细胞的增殖和分化而发挥免疫调节作用。
Abstract
Objective
2
To explore the expression regulation of adrenomedullin (ADM) in
Helicobacter pylori
(
H.pylori
) infection and its effect on the proliferation of CD3
+
T cells.
Methods
2
H.pylori
infection model was established in C57 mice and gastric epithelial cell lines (AGS and HGC-27). RT-PCR was used to detect the expression of ADM in the cells incubated with or without
H.pylori
. The protein levels of ADM
AKT and p-AKT were detected by Western blotting. The function of ADM on the proliferation of CD3
+
T cells were evaluated by flow cytometry.
Results
2
H.pylori
infection increased the expression of ADM in AGS cells and HGC-27 cells in a time-and dose-dependent manner (
P
<
0.05). While
blocking PI3K/AKT signal pathway reversed above increase induced by
H.pylori
(
P
<
0.05). Compared with uninfected mice
the infection also enhanced the ADM expression in the mouse gastric tissue. Compared with WT
H.pylori
infected AGS and HGC-27 cells
knockout of cagA resulted in decrease in ADM expression which was induced by
H.pylori
infection (
P
<
0.05). ADM induced the proliferation of CD3
+
T cells in a dose-dependent manner
and enhanced the expression of IFN-γ (
P
<
0.05).
Conclusion
2
H.pylori
infection up-regulates ADM expression through PI3K/AKT signaling pathway activation
and ADM exerts immunoregulatory effect by promoting proliferation and IFN-γ production of CD3
+
T cells.
关键词
Keywords
references
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