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:
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.
Role and mechanism of adrenomedullin expression in Helicobacter pylori infection
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
MARSHALL B J, WARREN J R. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration[J]. Lancet, 1984, 1(8390):1311-1315.
REZKITHA Y A, MIFTAHUSSURUR M, NUSI I A, et al . An East-Asian-type cagA Helicobacter pylori infected patient with clinical manifestation of gastric ulcer[J ] . Acta Med Indones, 2016, 48(4):307-313..
PARKIN D M, BRAY F, FERLAY J, et al . Global cancer statistics, 2002[J ] . CA Cancer J Clin, 2005, 55(2):74-108.
KANDULSKI A, SELGRAD M, MALFERTHEINER P. Helicobacter pylori infection: a clinical overview[J ] . Dig Liver Dis, 2008, 40(8):619-626. DOI:10.1016/j.dld.2008.02.026.
KITAMURA K, KANGAWA K, KAWAMOTO M, et al . Adrenomedullin: a novel hypotensive peptide isolated from human pheochromocytoma[J ] . Biochem Biophys Res Commun, 1993, 192(2):553-560. DOI:10.1016/j.bbrc.2012.08.022.
MARUTSUKA K, HATAKEYAMA K, SATO Y, et al . Immunohistological localization and possible functions of adrenomedullin[J ] . Hypertens Res, 2003, 26(Suppl):S33-S40.
GROSCHL M, WENDLER O, TOPF H G, et al . Significance of salivary adrenomedullin in the maintenance of oral health: stimulation of oral cell proliferation and antibacterial properties[J ] . Regul Pept, 2009, 154(1/3):16-22. DOI:10.1016/j.regpep.2008.12.007.
FUKUDA K, TSUKADA H, OYA M, et al . Adrenomedullin promotes epithelial restitution of rat and human gastric mucosa in vitro [J ] . Peptides, 1999, 20(1):127-132..
ALLAKER R P, KAPAS S. Adrenomedullin expression by gastric epithelial cells in response to infection[J]. Clin Diagn Lab Immunol, 2003, 10(4):546-551.
ZHUANG Y, SHI Y, LIU X F, et al . Helicobacter pylori -infected macrophages induce Th17 cell differentiation[J ] . Immunobiology, 2011, 216(1/2):200-207. DOI:10.1016/j.imbio.2010.05.005..
WANG T T, ZHAO Y L, PENG L S, et al . Tumour-activated neutrophils in gastric cancer foster immune suppression and disease progression through GM-CSF-PD-L1 pathway[J ] . Gut, 2017, 66:1900-1911.DOI:10.1136/gutjnl-2016-313075.
HU S X, ZHANG R B, YANG L X, et al . Research progress on genetic polym orphism and pathogenesis of Helicobacter Pylori[J ] . J Qiqihar Med Coll, 2013, 34(23):3520-3522.
HINSON J P, KAPAS S, SMITH D M. Adrenomedullin, a multifunctional regulatory peptide[J]. Endocr Rev, 2000, 21(2):138-167. DOI:10.1210/edrv.21.2.0396.
HIRSCH A B, MCCUEN R W, ARIMURA A, et al . Adrenomedullin stimulates somatostatin and thus inhibits histamine and acid secretion in the fundus of the stomach[J ] . Regul Pept, 2003, 110(3):189-195.
WIESNER J, VILCINSKAS A. Antimicrobial peptides: the ancient arm of the human immune system[J]. Virulence, 2010, 1(5):440-464. DOI:10.4161/viru.1.5.12983.
KRAVTSOV G M, HWANG I S, TANG F. The inhibitory effect of adrenomedullin in the rat ileum: cross-talk with beta3-adrenoceptor in the serotonin-induced muscle contraction[J]. J Pharmacol Exp Ther, 2004, 308(1):241-248.DOI:10.1124/jpet.103.057612.